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Abstract The Corneometer CM® 825 from Courage & Khazaka electronic GmbH is widely utilized in clinical efficacy testing of cosmetics. Assessing methodological variables is crucial for ensuring the reliability of the process. The aim of this study was to evaluate the operational and instrumental parameters of the Corneometer CM® 825 in the clinical assessment of skin hydration levels. Precision and accuracy of the measurements were assessed by measuring hydration levels on 10 participants in specific areas of the forearm and face. Three different skin conditions (dry, normal, and hydrated) resulting from the use or non-use of moisturizing cosmetics and a drying promoter were evaluated within 120 minutes of their application. The electrical capacitance method demonstrated good repeatability, with coefficients of variation mostly below 10%. However, higher variability was observed in inter-observer readings. The equipment exhibited high sensitivity and accurately discriminated the differences between hydrated and dry skin. Operational training and standardization of the methodology are essential to ensure accurate, reproducible, and reliable results in studies utilizing the Corneometer equipment for assessing skin hydration levels.

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Abstract L-theanine has neuromodulatory properties, such as attenuate anxiety disorders and stress. Stress is a situation characterized by the stimulus to cortisol secretion and without specific pharmacological therapies. Thus, this study investigates the effect of L-theanine on the response to acute stress, evaluated by tissue cortisol level, oxidative status markers, and behavioral parameters, in zebrafish. The animals were divided into six groups: G1: control, G2: treated with L-theanine 45 mg/L, G3: treated with L-theanine 100 mg/L, G4: stress, G5: stress+L-theanine 45 mg/L and G6: stress+L-theanine 100 mg/L. Before the execution of the acute stress protocol that consisted of chasing the animals with a net for two minutes, exposure to L-theanine was performed in aquarium water for 1 hour. Tissue cortisol levels were analyzed, as well as cerebral oxidative status (lipoperoxidation and levels of thiolic compounds) and fish behavior (new tank test). L-theanine at a concentration of 45 mg/mL modulated the effects of acute stress on zebrafish, inhibiting increased levels of tissue cortisol. However, it was not able to alter the behavior or oxidative status of the animals. Thus, we conclude that the administration of L-theanine can promote acute stress attenuation, modulating the pathological responses of stress.

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Abstract Drug addiction is one of the most important global problems. Medicinal herbs have been traditionally used in the management and treatment of opioid withdrawal syndrome and pain. The aim of this study was to determine the effect of A. dracunculus essential oil in reducing the symptoms of morphine withdrawal in mice. Male mice (25-30 g) were randomly assigned into 4 groups (n=10). Morphine-dependent groups received morphine (50 and 75 mg/kg ip; three times/day, 3 days) and a single injection of morphine (50 mg/kg) and then naloxone on the fourth day via IP injection. The control group received saline. The post-treated group received morphine for 3 days; on the fourth day, ten minutes before receiving naloxone, A. dracunculus essential oil with a dose of 75 mg/kg was injected. All groups received naloxone 2 hours after receiving the last dose of morphine; then, the morphine withdrawal symptoms were measured for 30 minutes. In the post-treated and co-treated groups, the body stretching and shaking the claw were significantly less than morphine-dependent groups (p<0/05). Also, in the post-treated and co-treated groups, the blinking, itching, and the number of standing on two legs significantly decreased compared to the morphine group. Hence, it might be concluded that A. dracunculus essential oil can significantly reduce morphine withdrawal symptoms.

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Abstract The aim of the present study is to develop a chitosan based herbal formulation using rhubarb for wound healing. Wound healing is a dynamic process facilitating the regeneration or repair of broken tissue. Rhubarb is commonly used worldwide for their effective antiseptic, antifungal and antiviral properties. Rhubarb loaded chitosan nanoparticles were prepared by ionic cross-linking process with sodium lauryl sulphate. The optimized formulation was examined for antibacterial activity against S. aureus and P. aeruginosa. Wound healing effects of the developed formulation was studied on excision wound model in Wistar albino rats. Average particle size and zeta potential of chitosan nanoparticles varied from 93 to 2,225 nm and from+30.82 to -16.08 mV, respectively. On the basis of particle size, zeta potential, and % entrapment, Formulation C 4 (0.0595% chitosan, 0.535% cross-linker, and 1% drug) was selected among different checkpoint formulation and further studies were performed. Hydrogel was developed using a combination of polyvinylpyrrolidone and carboxymethyl cellulose. Nanoformulation based hydrogel showed significantly enhanced antimicrobial activity against tested pathogenic microbial strains in comparison to drug solution, as well as marketed formulations.

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Abstract Entecavir is an inhibitor of hepatitis B virus (HBV) DNA synthesis that has been widely prescribed in the treatment of chronic infections caused by the virus. Production of generic ETV drugs is an ongoing global endeavor, with particular significance for developing countries that rely on importing the expensive reference drug. ETV-excipient compatibility studies were conducted with the declared inputs in solid pharmaceutical formulations on the market through thermal analysis and HPLC techniques. Thermal analyses by TGA and DTA indicated compatibility of entecavir with the excipients microcrystalline cellulose, crospovidone, titanium dioxide, magnesium stearate, hypromellose, polyethylene glycol and povidone; this was confirmed via HPLC. Lactose monohydrate proved to be incompatible with ETV in thermal and chromatographic assays. The thermal analysis of marketed solid dosage forms revealed a predominance of the lactose monohydrate profile at the expense of ETV and other inputs in the TGA and DTA curves, due to its high content in the formulations; this makes the evidence of ETV-lactose chemical interaction even more important. Compatibility tests by HPLC showed no chemical interaction of ETV with the excipient mannitol, a soluble diluent proposed as a replacement for lactose monohydrate, with the same function in the formulation.

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Abstract In this work, a methodology was developed to obtain dietary fiber from agro-industrial fruit and vegetable waste. The resulting raw material was named DF. The physicochemical analysis revealed a high total dietary fiber content, along with an appropriate soluble to insoluble fiber ratio and excellent water and fat retention capacity. Subsequently, its potential protective effect against hepatotoxicity induced by valproic acid (VPA) was investigated in Wistar rats, both as preventive and curative treatments. For this purpose, two different trials were conducted. In the preventive trial, VPA (250 mg/kg/day; oral) was administered concomitantly with DF (0.3 and 0.15 mg/kg/day) for 14 days. In the curative trial, VPA was administered for 14 days, followed by DF for an additional 14 days. The results demonstrated that DF supplementation normalized body weight, liver biomarkers and attenuated VPA-induced tissue damage, while normal liver architecture was preserved. These findings suggest that DF obtained from agro-industrial fruit and vegetable waste materials may serve as a functional feedstock to counteract the harmful effects associated with prolonged VPA treatment.

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Abstract The level of understanding about disease and treatment is an important factor to consider in achieving favorable outcomes in patients with mental disorders, and adherence to pharmacological treatment is crucial in this regard. The aim of this study was to assess to what extent patients with MD undergoing an integrated pharmaceutical care model with telepharmacy showed improvements in factors related to treatment adherence and their level of knowledge about pharmacotherapy. A parallel randomized clinical trial was conducted with a two-arm study in two Psychosocial Care Centers located in a state capital in Brazil. Participants in the intervention group received a comprehensive pharmaceutical care model that included attitudinal, technical, and educational interventions, while the control group received standard routine care. Predictive factors for adherence to pharmacological treatment and level of medication knowledge were assessed before and after the intervention. In the intervention group (33), significant improvements were found in the scores of adherence predictors (p<0.001) and the level of knowledge of pharmacotherapy (p<0.001) from baseline to follow-up, compared to the control group (33). The telepharmacy model demonstrated effectiveness in enhancing the scores of adherence predictors for pharmacological treatment and improving the level of knowledge of pharmacotherapy among patients with mental disorders.

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Abstract Belonging to the Alismataceae family, Echinodorus macrophyllus, known in Brazil as “chapéu de couro”, is popular in the food industry, where it is used in teas and infusions. The objective of this study was to evaluate the active chemical compounds in the powder of E. macrophyllus leaves extracted by two different methods (Soxhlet [SXT] and ultrasound-assisted extraction [UAE]), quantify the total phenolic compound (TPC) and total flavonoid (TFC) content, and evaluate the antioxidant potential and larvicidal activity. The SXT extraction was the most efficient (6.05% yield). Analysis by thin-layer chromatography (TLC) and high-performance liquid chromatography with a diode array detector (HPLC-DAD) evidenced the presence of cinnamic acid derivatives, flavones, and flavanones in the extracts. The TPC was higher in the SXT extract (7.71±0.05 µg GAE/mL). However, there was no significant difference in TFC. The SXT extract exhibited greater antioxidant potential according to the ferric reducing antioxidant power (FRAP) method (IC50=3.37±0.45 µg/mL), while the UAE extract showed higher activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50=42.16±5.79 µg/mL). Both extracts were nontoxic to Artemia salina, suggesting the potential health benefits of this plant, which is rich in phenolic compounds and diverse pharmacological properties.

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Abstract Hybrid structures containing multiple pharmacophore units with known activity have attracted attention due to their promising outcomes. In this study, several new hybrid structures containing benzimidazole and thiadiazole units were synthesized. The newly synthesized compounds were structurally analyzed using 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antimicrobial, in vitro anti-cancer, and antioxidant activities of all compounds were investigated. In vitro antimicrobial activities of the compounds were determined against Gram-positive (S. aureus ATCC 29213, E. faecalis ATCC 29212), Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) bacteria and fungi (C. albicans ATCC 10231) by using broth microdilution method. The compound 5g bearing 4-methoxyphenyl derivative showed the best activity with 32 μg/mL against S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. The MTT test was used to determine the cytotoxicity of the produced compounds on the MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines. FRAP method was used to determine the antioxidant properties of synthesized compounds. The Ferric Reducing Antioxidant Power of the compounds 5a, 5b, and 5c showed more antioxidant properties than vitamin E. The compound 5g stands out in the series in that it is not toxic on the healthy cell line and has promising antimicrobial activity.

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Abstract Mikania glomerata (guaco) is included in Brazil’s National List of Essential Drugs (RENAME) with expectorant and bronchodilator indications. This research aims to describe the profile of patients and prescribers of guaco-based herbal medicines within the Unified Health System in the municipalities of Rio Grande do Sul (RS)/Brazil, quantify the consumption and cost of this product, and assess the prescriber’s experience with guaco and herbal medicine. A cross-sectional observational study was conducted based on questionnaires applied to prescribers and guaco usage data in primary care in RS municipalities (May 1, 2020 - April 30, 2021). 44 municipalities (40%) were identified dispensing guaco syrup in the sample. The results showed a prevalence of women users (57.4%) and patients between 19 and 59 years of age (58.2%). All participating prescribers were physicians, and 37% of the responses indicated daily doses of coumarin lower than recommended. The syrup consumption per 1,000 inhabitants ranged from 0.3 to 36.6 bottles, and the monthly cost per municipality varied from $0.50 to $247.78. Only five prescribers (21.7%) were familiar with the herbal medicines in RENAME, and only one had formal training for prescribing herbal medicines, highlighting the need for instruction and dissemination of programs for using herbal medicines.

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Abstract Collagen, the predominant protein in various organisms, is pivotal for tissue structure and mechanical properties. It has been extensively studied for its cosmetic, surgical, and anti-ageing applications, reflecting a growing interest in collagen-based cosmetics in Romania and prompting further research in this area. The study aimed to assess collagen’s efficacy and safety in dermocosmetology, comparing collagen peptides’ effectiveness in oral and topical applications. An analysis of the published studies on the subject was carried out, comparing the effectiveness of using collagen in different ways to improve skin conditions. The investigation included a literature review on collagen’s role in enhancing skin properties, covering its discovery, structure, chemical composition, systemic and topical applications, diverse sources, and skin penetration mechanisms. Hydrolysed collagen and its antioxidant properties are considered. The methods of investigating and monitoring the safety of cosmetic preparations are described. It has been concluded that topical collagen, similarly to nutraceutical supplements with collagen peptides, can slow down and reduce the signs of skin ageing and can increase skin elasticity, density, and moisture in equal measure. Studies have confirmed the harmlessness of collagen beyond doubt, but further investigation is necessary to determine the effectiveness of using different types of collagen.

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Abstract The transdermal pathway serves as a significant route for achieving localized or systemic effects. Within this context, the stratum corneum is a crucial barrier limiting the permeation of many drugs. To surmount this barrier, carriers, and nanocarriers have been utilised, notably ‘invasome’ being one such example. In our study, we formulated invasomes loaded with simvastatin using the conventional thin-layer evaporation technique. This formulation involved the use of soy phosphatidylcholine, terpene (Limonene), chloroform, and ethanol. Simvastatin-loadedinvasomes were incorporated into a carbopol 934 solution to create a gel. We prepared and assessed different formulationsfor various parameters, including zeta potential, scanning electron microscopy, entrapment efficiency, viscosity, and drug content, and conducted in vitro studies. The entrapment efficiency was as high as 83.17±0.61%. The maximum in vitro drug permeation (45.44±0.4%) was found in the gel with 0.5% soy phosphatidylcholine and 0.25% terpene. Upon evaluating these parameters, our findings suggest that the simvastatin invasomal gel effectively enhances drug permeability across membranes and successfully achieves prolonged drug release.

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Abstract Caused by the protozoan Trypanosoma cruzi, Chagas disease affects six to seven million people worldwide, mainly in Latin America. The drugs currently available for treating the disease are ineffective during its chronic phase and have serious adverse effects. Essential for the survival of T. cruzi, the enzyme dihydroorotate dehydrogenase (DHODH) has become a key molecular target for drug discovery in Chagas disease. This study investigates the bi-dimensional and three-dimensional quantitative structure-activity relationships (QSAR) for a series of 64 T. cruzi DHODH inhibitors. The results indicate a highly predictive 2D Hologram QSAR (HQSAR) model (q 2 = 0.65, r 2 = 0.88, and r 2 pred = 0.82) that identified key molecular fragments that correlate with DHODH inhibition. Moreover, 3D Comparative Molecular Field Analysis (CoMFA) models (q 2 = 0.75, r 2 = 0.99, and r 2 pred = 0.66) pointed out the 3D molecular features that determine the activity of the inhibitors. Although restricted to a congeneric series and focused solely on 2D and 3D descriptors, these QSAR models and molecular docking analyses identified key properties and intermolecular interactions for designing and optimizing new compounds as potent T. cruzi DHODH inhibitors.

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Abstract The study aimed to assess the prevalence and characteristics of potential drug-drug interactions (pDDIs) that increase the risk of QT prolongation, in a population of cardiovascular disease patients. An observational retrospective study was conducted at a cardiology ward. A total of 351 patients were included in the analysis, with almost equal gender distribution (female 48.4%) and mean age 70±10 years. In the total set of tested drug pairs (5620), QT-prolonging pDDIs were identified in 13 drug pairs on admission. The highest frequency was observed for ciprofloxacin (involved in 5 pDDIs), followed by propafenone (4 pDDIs) and beta2-agonists (4 pDDIs). The pharmacodynamic mechanism was involved in all pDDIs. The study revealed a low prevalence of QT-prolonging pDDIs on admission to the cardiology ward, about 3% in the studied population. However, given that underlying heart disease is a significant risk factor for the occurrence of QTc prolongation, the additional risk for acquired QT prolongation should not be neglected. Due to serious consequences caused by QT prolongation and TdP, the key role of health professionals is to identify predisposed patients and to recognize pDDIs involving QT-prolonging agents. Hence, patients’ modifiable risk factors for QT prolongation should be minimized, if not eliminated.

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Abstract Tagetes minuta L. is a naturalized species that is not endemic to the high-altitude fields of Santa Catarina in southern Brazil. In this study, we investigated the composition of the essential oil (EO) from the flowers of the plant and its larvicidal activity against Aedes aegypti. The EO was obtained by hydrodistillation using a Clevenger apparatus. The chemical composition was determined using gas chromatography coupled with mass spectrometry (GC-MS). The EO extraction yield was 4.9%, and the major compounds (Z)-tagetone, (Z)-β-ocimene, and dihydrotagetone were identified. The 24 h larvicidal activity was verified against that of L3 larvae of the Rockefeller strain of Ae. Aegypti. The EO showed larvicidal activity against Ae. aegypti, with LC50 = 17.28 μg/mL-1. The results indicate that the bioinsecticidal potential of T. minuta EO is promising for the development of research in the field of natural products.

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Abstract Depression has substantially increased in the last 10 years in Brazil, and mental health became a concerning issue for the public health globally, especially considering the COVID-19 pandemic. The therapeutic conduct in depression mainly relies on medication and psychotherapy. However, more than one attempt in the treatment can be considered a common procedure before finding out the right medication. This conduct leads many patients to give up following pharmacological treatment. In this scenario, pharmacogenomics emerges as a possible supporting tool of the medical treatment. This paper aims to analyze the scenario of depression in Brazil and the viability of pharmacogenomic tests implementation as a part of the medical procedure. Official data bank from the Brazilian government was used to analyze the prevalence of depressive disorder, as well as Pharmacogenomic data bases and relevant articles around this topic. Additionally, pharmacogenomic tests typically take into consideration the genes CYP2D6 and CYP2C19, which are relevant for antidepressant treatment. Data shows that these tests could help patients achieve remission of symptoms, and they could also be economically advantageous. Thus, pharmacogenomic tests present as an interesting approach for the therapeutic conduct of depression and can significantly improve the health quality of this affected population.

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Abstract Healthcare during the COVID-19 pandemic may have led to the inappropriate use of antimicrobial agents and contributed to elevated multidrug resistance. The aim of this study was to analyze the consumption of antibacterial agents at a hospital complex from 2018 to 2021. Drug utilization study using antibacterial agents consumption data. The groups of antibacterial agents most consumed in the hospital complex were carbapenems, penicillins + beta-lactamase inhibitors, beta-lactamase-resistant penicillins, glycopeptides, and fluoroquinolones. The drugs with a compound annual growth rate that increased by more than 20% from 2018 to 2021 were amikacin (50.12%), benzylpenicillin (24.33%), oral clarithromycin (51.06%), daptomycin (34.38%), polymyxin B (20.85%), and tigecycline (41.49%). According to the AWaRE classification, the antibacterial agents from the Watch group subjected to AWaRE exhibited increased consumption in all years of the study. On the other hand, there was a reduction in the access category. In turn, the consumption of antibacterial agents in the reserve category also increased. The pattern of antimicrobial consumption in the hospital complex showed increased consumption in medical clinics and intensive care units, with a predominance of carbapenems, penicillins + beta-lactamase inhibitors, beta-lactamase-resistant penicillins, glycopeptides, fluoroquinolones, and polymyxin B, reflecting the care profile and influence of the COVID-19 pandemic.

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Abstract The study investigates the potential of Morus alba L. (mulberry) young and ripe fruit extracts against lung cancer cells. Cancer ranking as the second leading cause of global mortality, it is essential to investigate natural compounds like phytochemicals for therapeutic benefits. The research investigates presence of phytochemicals and antioxidant activity of both young (MAF-Y) and ripe (MAF-R) mulberry fruit extracts. Results revealed presence of various secondary metabolites, particularly high phenolic content and antioxidant properties in MAF-R. Both extracts demonstrated significant cytotoxicity against lung adenocarcinoma cells (A549), with IC50 18.4 ± 3.01µg/ml (MAF-R) and 29.41 ±3.6 µg/ml (MAF-Y). Moreover, the extracts effectively inhibited cell migration. Treatment of extracts elevated reactive oxygen species (ROS) production which resulted in disruption of mitochondrial membrane potential, and induced the process of apoptosis in lung carcinoma cells. This was evidenced through various assays including differential staining and DNA fragmentation analysis. These findings underscore the potential of mulberry fruit extracts as promising candidates for cancer prevention and treatment due to their antioxidant properties, cytotoxic effects, and ability to induce apoptosis in lung cancer cells.

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Abstract Antimicrobial drug resistance is a challenge to public health. Various microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, carbapenemase-producing Klebsiella pneumoniae, Pythium insidiosum, and Candida auris, have developed resistance to commonly used antimicrobials in infection disease treatments. Consequently, there is an urgent need to explore and develop novel therapeutic drugs. Natural products, particularly medicinal plants, have received attention in the quest for innovative treatments for various diseases. Plantago major is a plant endowed with several biological properties, such as antibacterial, antifungal, and healing actions. This study aimed to investigate the antimicrobial activities of the methanolic extract obtained from the leaves of P. major. Microdilution assays were conducted to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentration. Additionally, synergism with antimicrobial drugs was assessed using a time-kill curve analysis. A synergistic bactericidal interaction between the extract and imipenem was observed against carbapenemase-producing K. pneumoniae. For MRSA, a bacteriostatic synergism was noted in combinations of the extract with cephalotin and oxacillin. For C. auris, a fungistatic interaction was observed between the extract and amphotericin B. These results suggest the presence of bioactive compounds within the extract with therapeutic potential for combating infections caused by these microorganisms.

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Abstract Metformin hydrochloride (MTF) has pharmacological properties for managing inflammatory skin conditions. MTF is a hydrophilic medication. Accordingly, embedding MTF into lipid carriers for enhancing skin penetration presents a challenge. The study aims to optimize the loading of MTF into nanostructured lipid carriers (NLCs) using a 22 full factorial design, employing the solvent injection technique. The NLCs were evaluated for encapsulation efficiency, hydrodynamic diameter, zeta potential, and polydispersity index. Alkalinization of the aqueous phase (pH = 12.5) resulted in maximizing the entrapment of MTF within NLCs. Furthermore, the tested solid lipids impacted the encapsulation of MTF based on their hydrophilic-lipophilic balance. The optimized formulation is composed of a lipid phase incorporating beeswax (75 mg), oleic acid (25 mg), and Span 60 (1% w/w), and an aqueous phase comprised of 1% w/w Tween 80, pH 12.5. The selected formula attained an entrapment efficiency of 53.68 ± 0.27%, a particle size of 333.0 ± 6.4 nm, and a negative surface charge, indicating adequate particles` stability. DSC and Molecular docking analyses confirmed the MTF incorporation within the lipid phase. The outcomes emphasize the importance of optimizing investigations in developing a viable delivery system for MTF to boost its permeation across the skin layers.

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Abstract Traditionally, raw cow milk has been employed to treat acid and thermal burns due to its antibacterial, antibiotic, and antifungal properties. It also aids in preventing scarring and alleviating burn-related skin discomfort. This study focuses on evaluating a nanoemulsion cream made from casein extracted from raw cow milk for managing acid and thermal burns. Casein was isolated and used to create 2%, 5%, and 10% w/w nanoemulsion creams. Wistar albino rats were used to induce acid and thermal burns, and the healing progress was monitored by measuring wound contraction and epithelialization period. The results demonstrated significant wound healing effects of the casein creams (p<0.001) in acid burns, with the 10% w/w cream showing the highest epithelization rate in thermal burns. Raw milk also exhibited notable healing properties in acid burns. However, its effectiveness was relatively lower in thermal burns. This study suggests that raw milk and its casein-derived creams could be utilized as first-aid treatments for acid burns, though they may be less effective for thermal burns.

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Abstract The juice of blood oranges, especially those of the Citrus sinensis variety Moro, cultivated in the region of Sicily (Italy), is an increasingly popular drink due to its beneficial health properties, such as its ability to reduce abdominal fat, related to its anthocyanin constituents, especially cyanidin-3-O-glycoside (C3G), as demonstrated in pre-clinical and clinical studies. However, the dry extract of C. sinensis juice currently available at compounding pharmacies in Brazil includes samples from various countries, some of which may not have adequate climatic conditions for the production of anthocyanins. In this work, we investigated samples from the three major suppliers (reference, A1, and A2). The composition of the samples was analyzed by LC-UV and LC-MS, total anthocyanin content (TAC), antioxidant activity (DPPH assay), and in vitro anti-inflammatory effect, by NO production in macrophages. C3G was detected only in the reference sample (1.6%), the TAC values were 1.45%, 0.1% and 0.01% in the reference, A1, and A2, respectively. The reference and A1 showed similar antioxidant activity (EC50 of 45.6 and 62.4 µg/mL, respectively), while A2 showed lower activity (EC50 315.1 µg/mL). Only the reference sample showed significant inhibition of NO release, demonstrating the need for quality control of these commercialized samples.

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Abstract This research aims to create dabrafenib (DBF)-loaded nanosponges (NSPs) using β-cyclodextrin (β-CD) and diphenyl carbonate (DPC) as linker to improve oral bioavailability. DBF-loaded β-CD NSPs were synthesized by finely adjusting the molar ratio of β-CD to DPC and optimizing the stirring rate and duration using design methodology. After being loaded with DBF, the produced β-CD NSPs were characterized in terms of particle size, zeta potential (Z.P), polydispersity index (PdI), and drug entrapment efficiency (E.E). Studies on compatibility were carried out with FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential Scanning Calorimetry). Permeability, in vivo, and in vitro experiments were performed on the improved NSPs and the pure medication. After optimizing DBF-loaded β-CD NSPs, a formulation with a mean size of 158.0 ± 7.2 nm, PdI of 0.282 ± 0.0044, and E.E of 86.23 ± 2.45% was obtained, based on the assessments indicated earlier. Zeta sizer, SEM, spectrum analysis, in vitro release, and pharmacokinetic tests were among the other analyses that further validated the optimization. An area under the curve (AUC0-t) of 7.95-fold greater and a Cmax 7.356 times higher than those of the free drug was demonstrated by the optimized β-CD NSPs, which showed a notable boost. The use of DBF-loaded NSPs holds promise as an effective strategy for enhancing release and bioavailability in the treatment of melanoma.

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Abstract Epilepsy affects around 50 million people worldwide, with 30% of them being refractory epilepsy. This shows that there is still a need for novel anti-seizure medication that have different mechanisms. One of the most common types of refractory epilepsy is temporal lobe epilepsy. Among the several effects of seizures on neurons is an increase in intracellular Ca2+ and activation of RhoA. Rapamycin is mTORC1 inhibitor, but long-term exposure to rapamycin (>18 hours) could also inhibit mTORC2. RhoA signaling pathway is regulated through the mTORC2 pathway; thus we hypothesized that long-term exposure to rapamycin could inhibit intracellular Ca2+ and RhoA activity as one of the mTORC2 downstream proteins, in a temporal lobe epilepsy model. This study used organotypic hippocampal slice cultures (OHSC) which were exposed to 20 nM rapamycin treatment for 3, 5, 8, and 10 days after induction of epilepsy by 7 μM kainic acid administration for 48 hours. Intracellular calcium concentration was observed using CLSM and RhoA activity with western blot. The results obtained from this research were long-term administration of rapamycin can decrease intracellular calcium concentration and RhoA activity in OHSC models of epilepsy induced by kainic acid, with the most effective duration is 5 days of exposure to rapamycin.

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Abstract Skin oxidation can impair physiological functions and induce skin diseases, such as photoaging and cancer. L-ascorbic acid (L-AA), or vitamin C, is commonly used in cosmetics because it is a potent antioxidant, inhibits melanogenesis, and promotes collagen and elastin synthesis in the skin. This study developed strategies to improve the stability of L-AA in its pure form with or without caffeic acid (CA) and evaluated its clinical efficacy using an ex vivo method. Oil/water emulsions were prepared with antioxidants and normal stability tests were conducted (various temperatures for 360 days). Antioxidant activity was assessed using a DPPH assay, and L-AA content was quantified by high-performance liquid chromatography. The thiobarbituric acid reactive substances method characterized the inhibition of lipid peroxides in the stratum corneum ex vivo. The formulation F1 (base + 10.0% L-AA) exhibited better L-AA stability over 360 days. The formulations F1 and F2 (base + 10.0% L-AA + 0.2% CA) increased the production of lipid peroxides when applied to the stratum corneum ex vivo and irradiated; however, when not irradiated, they inhibited the production of reactive oxygen species. For greater clinical efficacy of vitamin C on the skin, nighttime use is suggested as well as storage at low temperatures.

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Abstract Hydroxychloroquine (HCQ) is a chiral drug used to treat malaria and inflammatory diseases, available as a racemic mixture of R-and S-HCQ. This work aimed to build physiologically-based pharmacokinetic (PBPK) models to predict the pharmacokinetics (PK) of R-and S-HCQ and assess the impact of major genetic polymorphisms on PK. Whole-body PBPK models accounting for first-order absorption, Rodgers and Rowland distribution method, and enzyme kinetics data were built for R-and S-HCQ. The models were verified by comparing predicted PK parameters with observed ones, with a mean error within the acceptable range (0.5-2 fold). Simulations covered CYP2D6 normal metabolizer (NM), poor metabolizer (PM), and ultra-rapid metabolizer (UM) phenotypes, as well as CYP2C8 NM and PM phenotypes. The results revealed a 1.1-fold increase in area under the curve blood concentration versus time (AUC) for CYP2D6 PM individuals and a 0.9-fold reduction for UM individuals compared to NM individuals. In addition, simulations with CYP2D6 and CYP2C8 PM phenotype individuals combined with the CYP3A4 inhibitor clarithromycin showed increased AUC for R-and S-HCQ of 2.34 and 2.68, respectively. These PBPK models offer reliable predictions for R-and S-HCQ enantioselective kinetics and shed light on previously unexplored scenarios.

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Abstract The Covid-19 pandemic, caused by SARS-CoV-2, was responsible for millions of deaths worldwide. The main protease (Mpro) of SARS-CoV-2 is considered one of the important drug targets for the treatment of Covid-19. Recent studies have shown that anisotine should be a potent Mpro inhibitor. In the present work, four oxoquinoline derivatives are proposed as candidates for Mpro inhibitors. The main functional group of these derivatives shows similarity to anisotine, and they are active against the HSV-1, as well as the latter. Molecular docking studies evaluated whether these compounds could be active against Mpro of SARS-CoV-2. Structural modifications were proposed on the oxoquinoline derivative which formed a more stable complex with Mpro and this proposal formed an even more stable complex besides exhibiting improvements in the toxicological profile. Molecular dynamics simulations indicated that derivatives proposed promote greater stabilization by complexing with Mpro than anisotine.

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Abstract Melatonin straddles the boundary between food supplements and medicine. In Portugal, its classification is contingent upon a critical dosage threshold of 2 mg. This study aimed to detail the composition of melatonin-containing food supplements, available in Portugal based on their labels, and report the number of potential intoxications. Data was collected from 44 food supplements, and the difference in active ingredients was revealed towards the 16 approved medicines. Data on melatonin intoxication cases from 2018 to 2022 were obtained from the Portuguese Poisons Information Center (CIAV). Melatonin supplements, available in tablets, capsules, gummies, powders, or sprays, exhibited a recommended daily dose ranging from 1 to 1.95 mg. Only 20% contained melatonin alone, while the majority included plant extracts and vitamins. The absence of clinical studies supporting the efficacy of melatonin combined with plant extracts in these formulations raises concerns about their evidence-based effectiveness. Medicines contain 2 to 3 mg of melatonin per tablet, either immediate or modified release. Melatonin intoxication occurs mainly in children, with a higher prevalence between the first year of life and the age of four. Food supplements containing melatonin and plant extracts should be more carefully studied, including the potential adverse effects.

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Abstract This study is committed to searching for inhibitors of deacetylase SIRT2 within the natural product database via computer-aided drug design techniques. A comprehensive computer-aided drug design platform has been successfully established by integrating various techniques such as drug-likeness screening, pharmacokinetic prediction, molecular docking, and molecular dynamics simulation. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (YaTCM) has been thoroughly explored to identify SIRT2 inhibitors, and the discovered compounds have been validated using molecular dynamics simulation. Through the computer-aided drug design method, five compounds capable of binding to SIRT2 have been successfully screened out from 47,696 natural product compounds derived from 6,220 herbs in the YaTCM database. Molecular dynamics simulation reveals that Artonin E and Paleatin B can form stable receptor-ligand complexes in the active pocket of SIRT2 inhibitors. Based on computer-aided drug design and virtual screening and verification techniques, Artonin E and Paleatin B have been identified as inhibitors of SIRT2, which is a key therapeutic target for the treatment of neuroblastoma. Applying computer aided drug design techniques to identify potential drug molecules from natural products holds profound significance for drug research.

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Abstract Rifampicin (RFP) is used for the treatment of chronic bone tuberculosis owing to its powerful and wide spectrum antibacterial activities. However, effective concentrations of RFP required to treat bone tuberculosis are maintained for a short time in vivo, and adverse reactions and bone defects may occur after surgery. Therefore, the construction of a new drug delivery system to overcome these problems is required. In this study, we designed, constructed, and demonstrated the applicability of a calcium phosphate cement scaffold loaded with RFP liposomes for the treatment of bone tuberculosis. RFP liposomes were prepared using a film dispersion method. The preparation method was optimized using the encapsulation rate as an indicator and the morphology, mean particle size, zeta potential, encapsulation rate, and drug loading of RFP liposomes were characterized. Calcium phosphate cement scaffolds were constructed using 3D printing technology and used as RFP liposome carriers for sustained-release drug delivery. Finally, some of the properties were verified in vivo through experiments in rabbits. The results indicated that composite scaffolds can provide sustained drug release and are a promising treatment option for bone tuberculosis.

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Abstract Sjögren’s syndrome (SS) damages exocrine glands, and Lilium brownii var. viridulum Baker (Lilii Bulbus, LB) shows potential as a therapeutic agent. This study evaluated LB’s efficacy in alleviating xerostomia using non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and human salivary gland acinar (NS-SV-AC) cells. In vitro, NS-SV-AC cells were treated with LB (1, 5, 10, 50, and 100 µg/mL) and 5-aza-2′-deoxycytidine (2 µM/mL) for 48 h. Cell viability, fluid secretion, and aquaporin-5 (AQP-5) expression were assessed. In vivo, thirty 20-week-old NOD/SCID mice received LB orally (100, 500, and 1,000 mg/kg) for 4 weeks, with salivary secretion rates measured. AQP-5 and M3 muscarinic acetylcholine receptor (M3R) expression and inflammatory mediator levels were determined using western blotting and enzyme-linked immunosorbent assay. Histopathological examination of salivary glands was also performed. LB significantly increased NS-SV-AC cell proliferation, fluid secretion, and AQP-5 expression. In NOD/SCID mice, LB reduced anti-SSA/Ro and anti-SSB/La antibodies, tumor necrosis factor-α, interferon-γ, and interleukin-6, while increasing AQP-5 and M3R expression. This resulted in increased salivary secretion and reduced glandular inflammation. LB extract appears promising for managing oral health by enhancing salivation, upregulating AQP-5, and modulating immune-inflammatory responses.

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Abstract Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Herein, we investigate the anticancer potential of two multitarget CDK inhibitors viz. roscovitine (specific inhibitor of CDK1, 2, 7, and 9) and UCN-01 (pan CDK inhibitor) against three CRC cell lines. Both the drugs exerted cytotoxicity and inhibited clonogenic potential of human CRC cell lines. These drugs induced apoptosis, downregulated cell cycle regulatory and transcriptional CDKs and cyclins’ protein expression as well as their activity. Moreover, dual combination of either of these CDK inhibitors with standard chemotherapeutic drugs was found to be synergistic in CRC cells. Thus, we demonstrate that multiple CDK inhibition offers promising therapeutic strategy against CRC.

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Abstract Considering the unique role of medicinal chemistry in the pharmacists’ formation, in this work we assessed the impact of medicinal chemistry teaching on the interpretation of a clinical situation using statistical and learning gain analysis. Lectures were conducted with or without medicinal chemistry information about the drugs involved, and pre and post-tests were applied. Pharmacy students (n = 35) were divided into two experimental groups (control and test) and presented with a case report selected from literature involving statin-related myopathy when a pre-test was applied. A lecture containing pharmacological information on statins was delivered to the students from the control group. In contrast, the test group received the same information, but medicinal chemistry elements of statins were inserted, and afterward post-test was applied. The scores from the pre-test and post-test were statistically evaluated and used to calculate Cohen’s d, Hake’s, and Dellwo’s G learning gains to compare the performance of the students from both groups. The results showed that students from the test group obtained significantly higher performance in the post-test and higher learning gain values. In summary, medicinal chemistry elements provided important knowledge to unveil the reported clinical situation and to provide skills for adequate drug selection to avoid statin-related myopathy.

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Abstract Cancer is defined as a group of diseases in which abnormal cells multiply and can invade other organs, requiring continuous studies for new drugs. A series of 177 imidazo[1,2-a]pyridine and imidazo[1,2-a] pyrazine synthetic derivatives were previously obtained, and their anti-melanoma IC50 values have been determined. Here, Artificial Intelligence algorithms were used to select molecular descriptors and build a QSAR model, highlighting structural characteristics related to enhanced molecular potency. Additionally, the imidazopyrazine nucleus was compared to a known inhibitor of the Aurora Kinase enzyme, an important target in cancer therapy. Thus, strategic imidazopyrazines were subjected to comparative molecular dynamics calculations, providing inferences about their possible mechanisms of action. The QSAR model allows for the design and prediction of nine new analogues with favourable predicted IC50 values. Molecular dynamics simulations and the estimated binding energies are consistent with the ranking of activities presented by representatives of the series.

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Abstract This study was aimed to determine occupational and non-occupational exposure to benzene, toluene p-m-o-xylene (BTEXs) and butyl-acetate (nBA). The aim of this work was to develop a simple, sensitive, and reliable chromatographic method using urine, a non-invasive human sample. The method was applied to samples collected from furniture spray workers (n=53) who are at risk of exposure to BTEXs and nBA and office workers (n=51) who have no known exposure risk. Method validation tests, include the sensitivity (LOD≤0.018 ng/mL), precision (RSD≤4.1), accuracy (RE% (-3.9)-4.7), recovery (96.1-103.8%) and linearity (r2≥0.999). Urinary benzene (1.77 vs 1.23 ng/mL, exposed-control, respectively), toluene (51.22 vs 0.77 ng/mL), ethylbenzene (9.25 vs 6.69 ng/mL), para-xylene (1.73 vs 0.62 ng/mL), meta-xylene (2.58 vs 1.20 ng/mL), ortho-xylene (1.61 vs 0.88 ng/ mL), and butyl acetate (33.14 vs 1.63 ng/mL) concentrations were determined in the exposed and control group samples. Significant correlations were found between benzene (p=0.286*), ethylbenzene (p=0.552***) and o-xylene (p=0.292*) levels and smoking status in samples belonging to the control group. The occupationally-exposure-risk group samples have significantly higher BTEXs and nBA concentrations than the control (p<0.001). It was determined that smoking was a significantly effective factor in exposure to benzene, ethylbenzene and o-xylene in the control group.

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Abstract This is a commentary manuscript, which aims to carry out a critical analysis of the effects of Pharmaceutical Care (PC) without the continuity of the service by healthcare professionals. PC has proven to be a very effective practice for improving pharmacotherapy for medicine users. In Brazil, it is noticeable that in the vast majority of cases, PC is carried out by professionals who are already working within the healthcare systems under the supervision of researchers affiliated with universities, for the purpose of research and data collection. When the research ends there is no continuation of the service, which hinders its continuous implementation and the establishment of a connection with the community. It was observed that after discharge from pharmacotherapeutic monitoring, due to the interruption of the service, there was a deterioration in the clinical and laboratory parameters of individuals with chronic diseases. Therefore, it is clear that PC needs to be implemented not only for research purposes, but also in the “real world”, so that it is long-lasting and permanent with the monitoring of the patients using medication.

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Abstract In this study, we investigated the cerebroprotective effects of fenchone (FEN) against brain ischemia through in silico and in vivo approaches, focusing on the inhibition of nitric oxide synthase (NOS) and the modulation of oxidative stress markers. Molecular docking revealed the potential binding affinity of FEN for the NOS active site, with a binding energy of -6.6 kcal/mol. This was validated through molecular dynamics simulations over a 100 ns time frame, demonstrating stability and favorable interaction profiles. Wistar albino rats underwent bilateral common carotid artery occlusion/reperfusion (BCCAO/R) followed by FEN administration at doses of 100 and 200 mg/kg. Our results indicated a significant reduction in cerebral infarction size and improvements in electroencephalography (EEG) signal magnitude with FEN treatment. Additionally, FEN restored the activity of antioxidant enzymes (catalase and superoxide dismutase) and decreased malondialdehyde (MDA) and nitric oxide (NO) levels and infarct size compared to those in untreated ischemic rats. Histological analysis further corroborated the neuroprotective effects of FEN, demonstrating the structural preservation of neurons in the hippocampal CA1 region. Overall, the results suggest that FEN plays a neuroprotective role in brain ischemia, potentially through the inhibition of NOS, reduction of oxidative stress, and modulation of antioxidants, highlighting the potential of FEN as a therapeutic candidate for ischemic stroke management.

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The objective of this study was to investigate the relationship between the management capacity of Pharmaceutical Services and socioeconomic indices in Brazilian municipalities, analyzing which contextual factors are involved in its development. Data from a cross-sectional exploratory study at national scale and indicators were used to define the capacity of Pharmaceutical Services management. Pearson’s chi-square test and multivariate analysis were performed to associate Pharmaceutical Services management capacity with socioeconomic indices of each municipality. The results prove the existence of significant relationships between management capacity and socioeconomic indicators, suggesting that management capacity is influenced by the environment in which it operates. Municipalities that presented superior results were those with better socioeconomic indices and better conditions and structure of their healthcare system, reflecting a greater number of professionals, greater participation of popular social control and use of public resources. Municipalities with a smaller population size and lower socio-economic indices have less ability to manage pharmaceutical services, revealing worsening inequalities for its citizens. The existence of an adequate minimum structure, a qualified workforce, service organization, and opportunities for political articulation are essential for such municipalities to develop and improve their management capacity and obtain proper financing based on socioeconomic indicators to facilitate effective access to and adequate use of medicines for the population.

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To evaluate the clinical outcomes of supplementary prescribing by pharmacist in reducing blood pressure versus other models of care in patients who recently received medical diagnosis of hypertension. A 24-month pragmatic controlled trial was performed with 225 patients divided into three groups: control 1 (medical centered care), control 2 (pharmacist collaborative care without supplementary prescribing authority) and intervention (pharmacist collaborative care with supplementary prescribing authority). A comparison of values was performed at basal and after 24-months of follow up in each group and differences between groups. We applied the chi-square test, student's t-test for independent samples, one-way anova whenever appropriate. A p value < 0.05 was considered statistically significant. Significant reduction in sbp and dbp was verified in every groups; intervention group showed a significantly higher reduction in the mean blood pressure levels versus control 2 (δ vs. Control 2 group = -14.3 [ci95 % -12.6 to -15.9 mmhg] p = 0.006; δ vs. Control 1 group = -17.8 [ci95 % -13.8 to -19.8 mmhg] p < 0.001) and dbp (δ vs. Control 2 group = -8.9 [ci95 % -7.7 to -10.9 mmhg] p = 0.005; δ vs. Control 1 group = -9.8 [ci95 % -7.7 to -11.5 mmhg] p < 0.001). Intervention group also showed significantly higher reduction in ldl-cholesterol and total cholesterol, versus other groups. Pharmacist collaborative care with supplementary prescribing authority provided better results in the management of blood pressure, ldl-cholesterol and total cholesterol versus other models of care.

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The current study examined the effects of Diethylcarbamazine (DEC) on CCl4-induced liver toxicity and the autophagic process in mice. A dose of 50mg/kg of DEC was intragastrically administered for 12 days before the CCl4 (10%,v/v in olive oil, 2ml/kg) was administered via injection. Mice were euthanized 24h after the CCl4 injection. The rise in serum levels of NO and activity of glutathione reductase in CCl4-intoxicated mice were suppressed by DEC. Liver histopathology showed that DEC reduced the incidence of liver lesions induced by CCl4. In addition, DEC reduced the expression of TNF-α,IL-1β,IL-6,IL-22,NF-κB, MMP-9, COX-2 and iNOS in CCl4-treated mice. There was also a reduction in the expression of AKT and apoptotic cells. The expression of IL-10, IFN-γ, LC3 and PI3K increased in the DEC pre-treated group. The hepatoprotective mechanisms of DEC may be related to the attenuation of oxidative stress and anti-inflammatory activity. Thus, the impact of DEC on inflammatory and autophagic mechanisms becomes apparent, underscoring the importance of analyzing this drug's ability to induce improvements in acute toxin-induced hepatitis. Therefore, the conduct of this study is justified, as the development of new treatments and access to healthcare are paramount for the care of patients with hepatitis.

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In a pharmaceutical industrial environment, air quality control aims to find contaminations in the environment, which are used as an indicator of possible contamination of the product. Variables can be common quantities such as pressure differential, temperature, and humidity; or more complex quantities such as the number of particles suspended in the air and microbiological contamination. This set of controls in classified areas is called Environmental Monitoring. Monitoring the concentration of suspended particles in the air is detailed in the ISO 14644-2:2015 standard. This standard makes it mandatory for companies that have clean areas to control the number of particles suspended in the air as part of their environmental monitoring program and serves as a guide regarding the amount of concentration accepted for each type of clean area, as well as the classification of the clean room itself (ISO 14644-1). However, many features are not detailed in the ISO standard. The objective of this article was to review the main fundamentals related to particle counting in a pharmaceutical environment and to be used as a start point for professionals and academics starting studies in this area.

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Asparaginase (ASN) is a crucial drug in the treatment of acute lymphoblastic leukemia (ALL). However, it is associated with an important and unique toxicity profile compared to other types of chemotherapy. One of the most relevant toxicities is acute pancreatitis. Although it is frequently a reversible process, its severity may contraindicate the continued use of ASN, delay the entire chemotherapy regimen, and impact overall survival. So far, the pathophysiological mechanism that gives rise to this complication is not well defined. At the same time, some risk factors are being studied, mainly pharmacogenetic markers. This review will outline what is currently known about the main genetic polymorphisms associated with the risk of acute pancreatitis related to the use of asparaginase.

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In an alternative medicinal system, Matricaria chamomilla is used for various conditions like inflammation, higher cholesterol, wounds, diabetes and pregnancy-related issues. However, there is contradiction about the use of Matricaria chamomilla at the time of pregnancy. Therefore, the present study is designed to investigate the embryotoxic and developmental effects of Matricaria chamomilla using zebrafish embryos as a model. Matricaria chamomilla's chemical profiling was done using GC-MS/MS analysis. Fertilized embryos were selected and exposed to 0.1% vehicle (alcohol) and test medicine Matricaria chamomilla (mother tincture, 6C and 30C) for 96 hrs. Normal control group embryo exposed to embryo media. All the embryos were observed for mortality, hatching, morphological parameters and heart rate till 96 hours. GC-MS/MS analysis revealed 80 phytochemical compounds in hydro-alcoholic extract of Matricaria chamomilla. It exerted a mild effect on hatching rate and showed mortality than any other group. Whereas, after the exposure of Matricaria chamomilla-6C and 30C, there were no changes observed in all the parameters. Overall, the result reveals that Matricaria chamomilla-6C and 30C (at high dilution) is found safe and indicated its safety at the time of pregnancy. However, further validation in higher animal models is recommended for proper clinical correlation.

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The purpose of the present study is to prepare anise (Pimpinella anisum L.) seeds essential oil nanoemulsions using a full factorial experimental design. Tween 80 content (0.5-1%, X1), chitosan content (0.5-1%, X2), irradiation time (60-80s, X3) and ultrasonic amplitude (35-40%, X4) were selected as independent variables whereas mean droplet size (nm, Y1) and polydispersity index (Y2) as dependent variables. The accuracy of the generated mathematical models was evaluated using multiple linear regression. Moreover, oxidative stability during storage and antimicrobial activity of free and nanoemulsion anise seeds essential oil were evaluated. Experimental selected conditions were 80s irradiation time with 40% ultrasonic amplitude, stabilized with 0.5% chitosan and 1% polysorbate 80. The obtained results indicated the perfect nanodispersion of essential oil in water. Lastly, oxidative stability determined by the primary and secondary oxidation products and antimicrobial activity of anise seeds essential oil against various Gram+ and Grammicroorganisms were significantly increased after the nanodispersion. Hence, this study concludes that the mathematically modelled formulation of anise seed essential oil nanoemulsion systems, stabilized by polysorbate 80 and chitosan, exhibited significantly improved oxidative stability and antibacterial activity compared to the free essential oil.

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Novel anti-cholinesterase inhibitors including pyrazolone merging chalcone derivatives have been developed and molecular docking has been performed. From the docking results, compound 48 (-8.3 k/cal) shows the highest binding affinity toward the AChE enzyme compared to the standard drug donepezil (-12.76k/cal). This compound produced two conventional hydrogen bonds between the carbonyl oxygen and residue of Asn 491. Every synthetic chemical underwent screening to determine its ability to cause in vitro cytotoxicity activity against Human SH-SY5Y neuroblastoma cell lines. The cells of SH-SY5Y were preincubated for 30 minutes with varying doses of the chosen compounds like 8, 9, 10, 11, 31, 37, 44, 47, 48, and 50 to induce neurotoxicity. They were then grown in Aβ25-35 (25 mol/L) for 48 hr. Cell viability was determined by MTT assay. Compounds 8, 11, and 48 exhibited a better binding score -8.2k/cal -8.2k/cal and -8.3k/cal respectively compared to other analogs. Synthesized compounds 8, 11, and 48 inhibited Aβ25-35-induced apoptosis in SH-SY5Y cells and protected neural cells from damage. The MTT assay confirmed compound 48 significantly reduced Aβ25-35-induced toxicity among human neuroblastoma SH-SY5Y cells, demonstrating its neuroprotective properties.

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Tolvaptan is a BCS IV group compound that is insoluble in water and slightly soluble in all pH ranges. Therefore, it is important to increase its solubility and dissolution rate, thereby increasing its bioavailability. For this purpose, tolvaptan containing nanofiber formulations have been prepared to increase the dissolution rate and solubility. Hydrophilic polymers such as polyvinyl pyrrolidone, polyethyleneoxide, and Soluplus; solubilizing agents such as Labrafil M 1944-CS, Solutol HS15, Gelucire varieties, and cyclodextrin (CD) derivatives were used. SEM analyses, contact angle, wettability studies, porosity, and solubility studies were performed on the prepared formulations. The HPβCD-NF2 formulation prepared with polyvinyl pyrrolidone and Solutol HS-15 increased the water solubility of tolvaptan by 7.96 times, and it was chosen as the final formulation. More than 90% of tolvaptan in the HPβCD-NF2 formulation was dissolved within 20 min in different buffers (distilled water, pH 1.2, 4.5, 6.8) with and without sodium lauryl sulfate. The HPβCD-NF2 formulation did not have any cytotoxic effects on the Caco-2 cell line and increased permeability compared to the commercial product, according to Caco-2 cell permeability studies. An innovative tolvaptan nanofiber formulation with increased solubility and dissolution rate compared to pure tolvaptan was developed, and the HPβCD-NF2 formulation has the potential to be an alternative to a commercial product.

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The COVID-19 pandemic has had a devastating socioeconomic impact and reignited the debate on vaccination and the hesitancy to vaccinate children and young people. This study sought to understand the reasons related to the behaviour of parents in vaccinating their children aged 5 to 17 years against COVID-19 with currently available vaccines; this study was conducted from June 2022 to July 2022. This work was a cross-sectional, descriptive, and observational study with a qualitative‒quantitative approach. The individuals in the sample had a mean age of 12 years, were mostly public school students, did not have COVID-19, and had a complete vaccination card. Parents who had vaccinated their children reported understanding that vaccination supports immunity, whereas those who had not vaccinated their children did not trust the COVID-19 vaccine. The ability to recognize fake vaccinerelated information was greater among parents who vaccinated their children (72.4%) than among those who did not (38.0%; p<0.05). The behaviours involved in vaccinating against COVID-19 are multifactorial, and factors such as children’s age, lack of confidence in the efficiency and safety of vaccines, parents’ age, ability to use information appropriately for health decision-making and low ability to recognize fake vaccine-related information are involved in these behaviours.

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A series of second-generation compounds analogous to Santacruzamate A were designed, synthesized, and evaluated for their selective cytotoxic activity against the breast cancer cell line MDA-MB-231 (ATCC HTB-26). Compound 7 demonstrated the highest cytotoxicity and selectivity among the tested compounds, with an IC50 value of 8.30 μM, comparable to those of the positive controls cisplatin (8.46 μM) and etoposide (12 μM). In silico studies identified histone deacetylase 8 (HDAC8) as a potential target of compound 7, supporting its role as an HDAC inhibitor. Experimental data further confirmed the pro-apoptotic activity of compound 7, as it significantly increased caspase-3 and caspase-9 activities, along with TP53 and BAK expression compared to the untreated group. These findings indicate that compound 7 induces apoptotic cell death in tumor cells through the intrinsic mitochondrial pathway. This study highlights compound 7 as a promising candidate for further exploration as a selective anticancer agent targeting breast cancer cells.

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Rosmarinic acid is an indigenous antioxidant molecule derived from a variety of widely available herbal plants. This molecule exhibits a diverse array of pharmacological properties. Recently, there has been an increasing interest in the importance of its effects and its possible use as a natural antioxidant in processed foods. It is a naturally-occurring hydroxylated compound that is commonly found in species. The escalating emergence of antimicrobial resistance and the detrimental repercussions resulting from the excessive utilization of antibiotics are generating a need for novel antimicrobial therapies. Researchers are currently investigating natural compounds as a promising option in this context. Medicinal plants possess a substantial quantity of rosmarinic acid. It is widely used as a spice in various cuisines and is highly regarded in traditional medicine for its healing properties. Rosemary contains significant amounts of powerful antioxidant chemicals, such as phenolic diterpenes, flavonoids, and phenolic. This review aims to analyze the relationship between the structure and activity of Rosmarinic acid, as well as its chemistry, sources, biotechnological production, and neuroprotective effect. Additionally, it will focus on the nano formulation and commercialized formulations of Rosmarinic acid.

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The study explores the potential of Hygrophila auriculata, also known as “Ikshugandha” in Ayurvedic literature, to alleviate insomnia by extracting phytoconstituents and investigating its in-vivo sedativehypnotic activity. GC-MS analysis of seed and leaf extracts revealed the presence of phytoconstituents like β-stigmasterol, lupeol, and gamma-sitosterol. The receptor alpha1-beta2-gamma2 subtype in combination with GABA and diazepam was selected for the docking investigation. The highest docking scores were -9.46 Kcal/mol for stigmasterol and -9.40 Kcal/mol for lupeol. The in-vivo sedative-hypnotic activity was assessed using the Hole cross test, Hole board test, open field test, and the thiopental-induced sleeping duration test. The oral administration of ethyl acetate subextract and unsaponifiable fraction resulted in a significant reduction in the number of holes traversed and dips and a similar reaction for the open field test. In the thiopental-induced sleeping test, the hydroalcoholic extract, ethyl acetate subextract, and unsaponifiable fraction were observed to improve sleep time compared to the control group. The substance was considered safe up to 400 mg/kg for leaf extract and 200 mg for seed extract. These findings suggest the plant is a promising candidate for future pharmacological studies.

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This scoping review aimed to summarize studies that developed vancomycin dosing nomograms. A search was performed in MEDLINE, Embase, Scopus, LILACS, and Google Scholar for studies published from January 2009 until January 2014. Two authors performed the study selection and data extraction. Disagreements were resolved by the third author. Forty-three studies were included. Most of them were conducted in the U.S. (48.8%), developed for the adult population (81.4%), specifically for critically ill patients (39.7%), used population data as a method to create the nomogram (67.5%), considered the serum trough concentration as the pharmacodynamic target for developing the dosing nomogram (83.7%), chose intermittent infusion (76.8%) and recommended loading doses administration in their dosing nomogram (65.1%). Twenty-eight studies evaluated the dosing nomogram; 19 (67.8%) achieved optimal vancomycin serum levels. However, most studies were observational designs, with small sample sizes and few nomograms developed based on AUCguided dosing. Moreover, data on the clinical and microbiological outcomes of the patients enrolled in the studies are lacking. Vancomycin dosing nomograms were shown to be a valuable tool to guide the achievement of the PK/PD target, mainly in Middle-Income Countries. More robust methods for the development and evaluation of vancomycin dosing nomograms should be applied and associated with vancomycin TDM.

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Medication reconciliation has proven to be essential for patient safety. However, studies on its economic viability are still scarce. Therefore, the aim of this study was to understand the avoided cost of medication discrepancies identified through the medication reconciliation service at the hospital level. Single-arm intervention study, linked to the evaluation of return on investment. Patients admitted to a hospital from March to August 2020, who underwent a medication reconciliation service, were included. With regard to medication reconciliation, in the 102 pharmaceutical admissions of patients participating in the study, 62 discrepancies were found, being 37 (59.7 %) unintentional and 25 (40.3 %) intentional. A total of 49.0 % of interventions were accepted or partially accepted by the prescriber. The suggestion to include medication used at home in the prescription represented 78.0 % of the interventions. The total cost avoided from pharmaceutical interventions in unintentional discrepancies over the 60-day period was R$9,406.59 (US$1,802.03). A high number of unintentional discrepancies in hospital prescriptions was observed. The role of the pharmacist in reconciling medication has a relatively low cost compared to their relevant role in preventing errors and avoiding costs.

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This study evaluated the effects of gamma sterilization on a novel wound dressing composed of polyester-viscose gauze impregnated with an alginate hydrogel containing 10% v/v calendula glycolic extract. The investigation examined the impact of 15 kGy gamma radiation on the morphology and properties of the alginate-calendula wound dressing, including swelling, biodegradation, water vapor permeability, and pH. The HPLC fingerprint of gamma-irradiated calendula glycolic extract was also analyzed. Physicochemical properties of sterile and non-sterile dressings were characterized using scanning electron microscopy (SEM-FEG), X-ray diffraction (XRD), and thermal analysis. Both the non-irradiated and irradiated calendula glycolic extracts had similar chromatographic fingerprint profiles. Hydrogel coverage on the gauze fabric was observed in SEM images, along with slight surface modifications in the sterile dressing. XRD and thermal analyses presented peaks associated with the textile substrate and reduced weight loss due to water evaporation caused by sterilization. After irradiation with gamma rays, swelling (500-600%), biodegradation (70-80%), water vapor permeability (70-85 g/m.day.Pa), and pH (6.4) of dressings did not show any significant changes. Overall, the findings show that gamma radiation maintains the flavonoid content, moisture level, low biodegradation rate, and slightly acidic pH, which makes it an appropriate method for sterilizing the alginate-calendula wound dressing.

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The Ex-CSEPA model was developed to predict 30-day mortality for patients with hematologic malignancies after a standard 14-day antibiotic (ATB) treatment for Acinetobacter baumannii bacteremia. This study systematically evaluated the model’s performance in stratifying patientsinto high-risk and low-risk categories and compared the efficacy of extended ATB therapy with the standard 14-day course. The Ex-CSEPA model integrates several critical factors: extended course ATB (Ex), clinical improvement (C), starting ATB time (S), ECOG score (E), Pitt’s bacteremia score (P), and APACHE II score (A) to comprehensively assess mortality risk. The findings demonstrated that the Ex-CSEPA model effectively distinguished between high-risk and low-risk patients, with significant differences in mortality risks. High-risk patients had lower median survival compared to low-risk patients (p-value < 0.001), confirming the model’s accuracy. While extended ATB therapy did not improve overall survival rates, high-risk individuals benefited significantly. Extended ATB therapy reduced mortality by 32% and increased survival time by 66%, according to multivariable and Weibull proportional-hazards regression analyses. This study emphasizes the advantage of extended therapy for high-risk individuals and the usefulness of the Ex-CSEPA model in directing personalized treatment. In conclusion, the Ex-CSEPA model is a robust tool with substantial clinical implications, supporting personalized interventions with extended ATB therapy for high-risk patients and validating the standard 14-day course for low-risk individuals.

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To evaluate the pharmacotherapeutic interventions in antimicrobials, based on drug-related problems (DRP) implemented by the antimicrobial stewardship program (ASP). This is a posthoc analysis carried out between January 2018 and December 2019 in a University public trauma hospital. The DRP methodology was used to assess correct pharmacotherapy of antibiotics and acceptance by clinicians. Acceptability was defined as accepted within 24 hours, accepted after 24 hours, not accepted, or not accepted with justification. A total of 4,951 prescriptions were audited, of which an average of 16% of interventions resulted in 35.1% in unnecessary medication, 22.6% in administration route. For acceptability, all demonstrated significance according to P values <0.0001. In safety, 49.0% of interventions were performed, 42.0% were needed, and 9.0% were effective. DRP analysis is an important resource to be used within the ASP, bringing significant results both in terms of patient safety and cost minimization.

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Alpha-phellandrene (α-PHE), a cyclic monoterpene abundant in volatile oils, has anti-inflammatory and healing properties. A cutaneous formulation using this bioactive could provide benefits in wound healing. However, a simple method that quantifies α-PHE in the skin is still required. Thus, the study aims to develop and validate a high-performance liquid chromatographic (HPLC-UV) method to quantify α-PHE extracted from the skin. The method uses a reversed-phase C18 column (15 cm × 4.6 mm, 5 μm) and a mobile phase consisting of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) flowing at 0.5 mL/min. The phase concentration (A/B %) along the 40-min run time varied as described: 15/85 (0.01-10 min), 0/100 (10.1-20 min), and 15/85 (20.1-40 min). α-PHE was detected at 263 nm. The method was selective against skin and formulation interferents, linear (r = 0.9995) in a concentration range of 0.5-15.0 μg/mL, precise with an overall variation coefficient lower than 5.5%, accurately achieving recovery from the skin within 92-102%, and sensitive for the proposed application (detection limit = 0.05 µg/mL, quantification limit = 0.14 μg/mL). Finally, the validated method was tested in a skin penetration study, attesting to its success in developing topical formulations containing α-PHE.

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The objective of this study was to verify whether the test formulation of olmesartan medoxomil, in orodispersible tablet form, administered with water (treatment B) and without water (treatment C), presents a rate and extent of absorption equivalent to the reference formulation, film-coated tablet form (treatment A). Study design was monocentric, open-label, crossover and randomized. Olmesartan medoxomil 40 mg was orally administered, under fasting conditions to healthy participants. Blood collections were carried out over a period of 72 hours. Olmesartan plasma concentrations were determined by liquid chromatography coupled to mass spectrometry detector techniques. Pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf, Tmax, T1/2, Kel, %AUC_extrap were determined. Confidence intervals were constructed for the ratio of the geometric means between the test and comparator treatments (B/A and C/A) for Cmax and AUC(0-t), using ln-transformed data. Formulations were well tolerated, with no serious adverse events observed. The 90% CI for the B/A ratio was 89.50%-102.63% for the Cmax parameter and 89.72%-100.89% for the AUC(0-t) parameter, while for the C/A ratio it was 83.22%-95.40% for the Cmax parameter and 85.18%-95.77% for the AUC(0-t) parameter. In conclusion, the test formulation of olmesartan medoxomil, in orodispersible tablet form, administered with and without water, is bioequivalent to the reference formulation.

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This manuscript evaluates the influence of Momordica charantia L. fruit and seed extracts on B16-F10 melanoma cell lines. The study was concerned with the application of these extracts to the cell lines and subsequent, in comparison to a control group, examination of the resultant metabolite profiles. A comprehensive analysis of metabolites was conducted by employing state-of-the-art Q-TOF LC/MS methodology in which the mature fruit and seed methanol extracts of M. charantia were prepared. The extracts were applied to B16-F10 melanoma cell lines for 48 and 72 hours, after which the cell lines obtained were analyzed using a Q-TOF LC/MS using a C18 column (Poroshell HPH-C18,2.1x100mm,2.7 µm) with a gradient elution program. The raw data obtained was examined using various data analysis methods, and the identified metabolites were reviewed to investigate the potential relationship between the phytochemical components of extract and potential anticancer activity. Certain changes (the levels of L-carnitine, arginine, N-methyltryptamine, sphingosine, prostoglandin, tryptophan and urocanic acid) at the metabolome level were related to potential anticancer activity and antioxidant activity. This study demonstrated that the fruit and seed extracts of M. charantia induced metabolic changes, associated with anticancer activity, on melanoma cells through distinct pathways.

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Multilayer tablets are gaining popularity for combining active pharmaceutical ingredients in a single dosage unit. However, the need to personalize drug treatment frequently demands the subdivision of such dosage forms. This study aimed to evaluate the performance of commercial multilayer tablets from different geographic origins for subdivision. An analysis of morphology, dimensions, mechanical resistance, and mass measurements of the halves after subdivision by a tablet splitter was performed, as well as an analysis of the adhesion layers. The tablets failed to meet acceptable standards for mass variation (more than 10 % in over 60 % of the samples), mass loss, and friability (more than 3.0 and 1.5 % in half of the samples, respectively). Furthermore, most of the tabletshad exhibited layer separation or weakening after the subdivision, resulting in a marked decreasein fracture force to values below 10 N. Several factors, including matrix heterogeneity and high thickness, may contribute to these results. Delamination in multilayer tablets represents a significant quality issue that can compromise their therapeutic utility. Given such a scenario, the subdivision of multilayer tablets should be avoided until developers implement appropriate strategies, ensuring safe conditions for the user.

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Drug-drug eutectic system is a promising approach to provide in vitro and in vivo benefits. However, only a few eutectic combinations are reported with excellent pharmaceutical and therapeutical performances. In this work, two natural products, matrine and paeonol, were mixed and characterized on their eutecticity. Differences among the mixtures on microstructure, melting points and crystallinity were investigated by microscopy, differential scanning calorimetry and powder X-ray diffractometry. Potential intermolecular interactions between the two drugs, including van der Waals force and hydrogen bonds, were analyzed via molecular dynamic simulation and Fourier transform infrared analysis. Apparent solubility and oil-water partition coefficient of both drugs were changed due to the formation of eutectics. The matrine-paeonol eutectic system at a weight ratio of 4:6 showed a fast and synchronized drug dissolution profile, and increased AUC, MRT and Tmax values after oral administration in rats. Therefore, this study provides necessary evidence for design and application of the multidrug eutectic mixtures as an efficient strategy with great potentials on both formulation development and clinical application.

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The vasoconstrictor assay (VCA) has been internationally recognized as a reliable method to evaluate the bioequivalence of topical corticosteroids. The FDA has recommended its use since 1995 and ANVISA began to require this assay in 2022 (RDC no. 742/22). The objective of this study was to compare results from two VCA pilot studies, using two Konika Minolta® instruments and two different estimation methods. The Emax and ED50 parameters were obtained using a nonlinear mixed effect model and least squares fit using a Gauss-Newton algorithm. Regardless of the equipment or the fitting methods, similar Emax and ED50 were obtained. However, both parameters were different when comparing the assays performed from different batches of the same reference list drug (RLD) and procedures from the different guides. Added to this, the tests were carried out at different times and in different seasons. In the VCA pilot study, estimating the ED50 is essential to determine the D1 and D2 (shorter and longer dose duration reference standard calibrator) to be used in the pivotal bioequivalence study. The diversity of the Brazilian population and the lack of experience to perform the procedure represent major challenges for the implementation of this test.

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Cissus verticillata (L.) Nicolson & C.E. Jarvis, popularly known as “plant-insulin,” is used in Brazilian popular medicine for various conditions, including diabetes. Despite its usage, scientific research on its effects remains limited. In this regard, this study aimed to explore the potential anti-diabetic effects of C. verticillata’s aqueous extract (AECv) in mouse models of type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D was induced in Swiss mice via daily intraperitoneal administration of 50 mg/kg streptozotocin (STZ) for five days. Mice were then treated orally with saline or AECv (30 mg/kg/day or 300 mg/kg/day) for three weeks. After 18 days, behavioral tests were conducted, and glucose measurements were taken. To mimic T2D-like conditions, mice were fed standard rodent chow (SD) or a high-fat, high-fructose diet (western diet, WD) for 15 days and then received daily treatment with vehicle or AECv (300 mg/kg/day) for 21 days. Behavioral tests and a glucose tolerance test were then performed. AECv did not improve STZ- and WD-induced glucose impairments or anxiogenic- like behavior but significantly alleviated mechanical allodynia in both models. While AECv lacked hypoglycemic, anxiolytic, or antidepressant effects, it demonstrated the potential to enhance the pain sensitivity threshold.

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Antinuclear antibodies (ANAs) have recently sparked interest given their presence in cancer, including multiple myeloma (MM), a hematologic neoplasm characterized by abnormal plasma cell proliferation that accounts for approximately 1.6% of all cases of cancer. In our study, we performed ANA HEp-2 assays on samples from 44 patients with MM, 17 healthy controls, and a group of post-chemotherapy patients. Results revealed a significantly higher prevalence of ANAs in patients with MM than in controls (p = 0.0059). Most patients with MM exhibited relatively high ANA titers (≥1:80), and the most prevalent fluorescence pattern was the fine nuclear dot pattern. Notably, ANA titers decreased following chemotherapy, which correlated with the decrease in B2-microglobulin as well. Altogether, our results indicate potential links between a high prevalence of ANAs in patients with MM and frequent ANA positivity in metaphasic plaques.

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Growing concerns regarding the side effects of conventional drugs have heightened interest in medicinal plants as alternative therapeutic agents. Phyllanthus reticulatus, widely used in traditional medicine across Asia and Africa, is recognized for its diverse pharmacological properties. This study aimed to evaluate the potential antianemic effects of P. reticulatus in anemic rats. Fresh leaves of P. reticulatus were collected, air-dried, powdered, and extracted using methanol. The extract was subjected to phytochemical analysis and assessed for antianemic activity in 2,4-dinitrophenylhydrazine-induced anemic rats at doses of 250, 500, and 1,000 mg/kg body weight, with folic acid serving as the positive control. Hematological parameters, including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb) levels, packed cell volume (PCV), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV), were evaluated. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, saponins, phenols, and cardiac glycosides. Among the tested doses, P. reticulatus at 250 mg/kg demonstrated the highest efficacy, significantly increasing RBC count, Hb levels, and PCV, with effects comparable to those of the positive control. However, its influence on WBC count, MCHC, and MCV was comparatively lower. In conclusion, P. reticulatus exhibited promising antianemic potential by increasing RBC count, Hb levels, and PCV, suggesting its potential as a natural therapeutic agent for anemia.

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In this study, the reverse phase liquid chromatography (RPLC) method was preferred to determine the chromatographic behavior of phenytoin and valproic acid, the active ingredients of antiepileptic drugs. The optimization of the developed method was based on the capacity factor values of studied compounds in water-organic solvent mixtures varying in constant mobile phase pH value and the organic solvent concentration in the mobile phase where the compounds were analyzed. At constant pH, phenytoin was analyzed in acetonitrile-water binary mixtures containing 30-40% (v/v) acetonitrile, and valproic acid was analyzed in methanol-water binary mixtures containing 10-20% (v/v) methanol at 37oC. Kinetex EVO C18 Core-Shell (250x4,6mm I.D., 5µm) and Pinnacle DB Cyano (250 x 4,6 mm I.D., 5µm) columns were preferred for the quantitative determination of the compounds. Under all conditions mentioned in the method section, excellent linearity (r>0.99) was obtained in the concentration range of 10-40 μg/mL for phenytoin and 200-600 μg/mL for valproic acid. The recovery value of the method was calculated as 98.48% and 99.40% for phenytoin and valproic acid, respectively. In this study, an analytical procedure suitable for routine use was developed, and the method was validated for the determination of the amount of studied compounds in pharmaceutical dosage forms.

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This study aims to investigate the antiulcer effects of Idebenone (IDE) in Wistar rats with indomethacin-induced gastric ulcer and compare its effectiveness with famotidine (FAM). 36 rats were randomly divided into six groups: healthy; healthy+IDE200; ulcer (U); U+FAM; U+IDE100; U+IDE200. Six hours after the administration of 25 mg/kg of indomethacin, the antiulcer effects of FAM (40 mg/kg) and two different doses of IDE (100 and 200 mg/kg) in the gastric tissue of rats were examined through macroscopic, biochemical, molecular, and histopathological analyses. Comparative assessments were conducted between the healthy control group and the group treated with indomethacin alone. IDE effectively suppressed the indomethacin-induced increase in malondialdehyde (MDA) and mitigated the reduction in glutathione (GSH) levels. Furthermore, IDE treatment led to a significant decrease in mRNA expressions of interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa beta (NF-κB)-p65 in ulcerative rats. Histopathological examinations revealed that both IDE doses improved the ulcer damage caused by indomethacin in the rats' stomach tissues. This study demonstrates that IDE administration exhibits a protective effect against indomethacin-induced gastric ulcers by reducing oxidative stress and inflammatory processes. IDE’s potential to prevent ulcer formation in the gastric tissue of rats suggests that it could be a valuable therapeutic agent in clinical practice.

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Orlistat(Orli) is a safe and effective drug for obesity treatment approved by the Food and Drug Administration (FDA) in the US. Recently, Orli has been reported to exert considerable antitumor effects in amount types of malignancy. However, its role in osteosarcoma (OS) progression and its clinical significance in tumor therapy such as immune therapy remains largely unknown. In this study, we detected the effect of Orli exerted on OS progression using CCK-8 assay, wound-healing assay, Enzyme-linked immunosorbent assay (ELISA), cell transfection and xenograft growth assay. The result indicated that by upregulating Serpin Family F member 1 (SERPINF1), a multifunctional protein, OS inhibited OS progression via suppressing proliferation, colony-forming, migration and angiogenesis ability of OS cells in vitro and in vivo. More importantly, Orli potentiated programmed death1 antibody (PD1ab) immune checkpoint blockade therapy and may candidate as a potential drug in OS therapy.

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Facial aging involves natural processes such as bone resorption, subcutaneous volume loss, ligament laxity, and skin flaccidity. Currently, many aesthetic treatments are used to attenuate or delay the signs of facial aging, including facial exercises. They intend to improve skin elasticity, muscle tone, collagen production, and add (or reduce) volume of specific regions of the face. This study evaluated the effectiveness of a cosmetic formulation with ascorbyl tetraisopalmitate and synthetic tripeptide, combined with facial muscle exercises, in 43 healthy women aged between 30 and 65 years old. Participants were randomized into 3 groups: cosmetic formulation, cosmetic formulation + facial exercises, and facial exercises only. Instrumental measurements and self-assessment questionnaires were used to evaluate skin parameters. Significant improvement in skin firmness and elasticity were observed and attributed to the use of the cosmetic formulation. Additionally, participants noticed qualitative improvements in the appearance of their overall skin and wrinkles. High satisfaction scores were recorded for the facial exercise device and the formulation applied in the study. In conclusion, the cosmetic formulation had a positive impact on skin health, and the association of facial exercises, within time and conditions of this study, did not significantly increase the results caused by the formulation.

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The aim of this study is to analyze the glycemic control of patients with type 1 diabetes mellitus (T1DM) in insulin analogues use through judicial litigation in the Public Health System. A cross-sectional study was conducted with patients who have T1DM and acquire insulin analogues through judicial litigation in a Brazilian city. The patients who agreed to participate underwent laboratory tests of fasting blood glucose and glycated hemoglobin (HbA1c) and answered validated questionnaires about attitudes and skills towards the insulin application. The female gender predominated (n=22; 53.7 %) with a mean age of 32.3 ± 13.0 years. The average fasting blood glucose and HbA1c levels were 175.2 ± 67.8 mg/dL and 8.7 ± 1.7%, respectively. The monthly expenses on insulin for these patients was US$47.4 ± 28.4. Considering the HbA1c levels, the vast majority of patients did not have glycemic control of the disease (90.2 %) and most did not perform the correct insulin application technique (73.7 %). The use of more expensive insulins and the expense of more financial resources were not associated with better glycemic control of T1DM patients.

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Adherence to tenofovir-based antiretroviral therapy is crucial for treatment success. In this study, we evaluated tenofovir urine concentrations in a cohort of patients that answered standardized adherence questionnaires Morisky-Green and Brief Medication Questionnaire (BMQ). Adherence evaluations were related to the patients’ viral load. Among the 72 patients who completed the questionnaires, 70 provided urine samples, and 88.6% of them had an undetectable viral load. Among the patients who provided urine samples and completed the Morisky-Green questionnaire, 45.7% were categorized as having high adherence, 54.3% as medium adherence, and 2.9% as low adherence. Utilizing a ROC curve (area under the curve of 0.864, CI 95% 0.757-0.971), a tenofovir urinary concentration of 6288.5 ng/mL was established as the cutoff value to predict high adherence according to the BMQ. This cutoff demonstrated a sensitivity of 93% and specificity of 72% in predicting high adherence according to the BMQ, with 73.5% of patients enrolled in the study categorized as having high adherence. When comparing adherence levels determined by the BMQ and urinary concentration, a moderate kappa index was observed (0.677, p<0.01). The results suggest that urine tenofovir concentration measurement as a feasible and efficient strategy to monitor adherence during HIV treatment with this drug.

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Abstract Pathogenic strains of Escherichia coli can cause gastrointestinal infections, urinary tract infections (UTIs), bacteremia, and other severe infections. Some isolates of this species are capable of producing extended-spectrum β-lactamase (ESBL) enzymes, which mediate resistance against penicillin derivates and cephalosporins. Fungi of the Ascomycota phylum are known to produce antibiotics from different classes with activity against various bacterial agents. Among them, the genera Penicillium, Cephalosporium, Acremonium and Fusidium are known for the production of antimicrobial substances such as penicillin derivates, cephalosporins and fusidic acid. Currently, the search for new antimicrobials produced by species of the Ascomycota phylum includes the assessment of less explored habitats including aquatic environments, extreme environments, and the interior of plants/animals. The genus Penicillium remains promising for the discovery of new antimicrobial substances against resistant bacteria. In addition, those fungi have also been investigated regarding their usefulness for the biosynthesis of nanoparticles with antimicrobial activity. This narrative review introduces clinically relevant Escherichia coli pathovars, the historical contributions of the phylum Ascomycota to the production of antimicrobials, aspects of bioprocesses in the production of antimicrobial metabolites and different approaches of research targeting new antimicrobials such as screenings for fungi in environments not yet studied and the green synthesis mediated by fungi with antimicrobial activity.

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Abstract This study aimed to analyze the effectiveness of using an antivenom serum (AVS) premedication protocol to prevent early adverse reactions (EAR). This is a cohort study conducted with data from the Londrina Information and Toxicological Assistance Center (CIATox-Londrina) at the University Hospital of the State University of Londrina (HU-UEL), which included patients treated with AVS between January/2017 and December/2021. The independent variable was performing the premedication protocol and the dependent variable was the occurrence of EAR after AVS administration. Patients were followed until hospital discharge. The association analysis was performed with calculation of the Relative Risk (RR) and 95% Confidence Interval (95% CI). A total of 806 cases of accidents with venomous animals were analyzed. The minority (8.1%; n=65) had EAR, and the most frequent symptoms were related to dermatological and respiratory manifestations. The AVS premedication protocol was performed in 96.6% (n=734) of the cases. There was no statistically significant difference in the unadjusted (RR: 1.487; 95% CI: 0.530-4.174) and adjusted (RR: 1.482; 95% CI: 0.522-4.210) models regarding the performance of the AVS premedication protocol and the occurrence of EAR. It is recommended against AVS premedication given the lack of effectiveness in preventing EAR.

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Abstract The increasing interest in bioactive peptides (BPs) for their potential in disease control and health promotion has been accompanied by a lack of scalable processes for their purification, hindering their commercial production. Membrane filtration, especially using polymeric membranes (PMs), has emerged as a promising technique for BP separation due to its excellent separation performance, ease of fabrication, and flexibility. By utilizing natural sources, such as chitosan, cellulose, lignin, gelatin, alginate, keratin, and silk fibroin, in PM production, the environmental impact of membrane-based separation processes can be reduced while maintaining sustainable, eco-friendly approaches. Natural polymer membranes have exhibited excellent separation performance in terms of molecular weight cut-off and rejection of unwanted compounds, and their performance can be further improved by combining them with nanoparticles or other polymers. This review presents the recent updates on the use of PMs derived from natural sources for the separation of BPs, covering the production and functions of BPs, different membrane separation technologies, and challenges faced during downstream purification.

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Abstract To evaluate the neuropharmacological profile of new spiro thiazepinone and thiazolidinone compounds in CD1 mice after a computer-aided virtual screening based on a GABA-A/BZD site. From a library of 240 pyrazolo[1,4]thiazepin-3-ones and 39 pyrimidinyl thiazolidin-4-ones, two molecular prototypes of each series were selected by virtual screening using the rank consensus molecular docking approach, based on the GABA-A/BZD site. These compounds, coded as cpTP-0, cpTP-1, TAP-2 and cpTAP-2, were synthesised by multicomponent reactions and evaluated by neuropharmacological screening in CD1 mice (100 mg/kg, p.o.). The study revealed that cpTAP-2 exhibited a significant reduction of immobility time during the forced swimming test (FST), while it did not show any major effects in the rota-rod, open field, plus maze, tail suspension, pentylenetetrazole seizures, and barbiturate sleeping time tests. In a dose-response evaluation, cpTAP-2 reduced immobility time during forced swimming test in CD1 male mice at doses of 100 and 300 mg/kg with biologically relevant effect sizes. These results suggest that cpTAP-2 could elicit antidepressant effects possibly related to GABA-A/benzodiazepine site, although other mechanisms could be implicated.

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Abstract To synthesize the evidence about pharmacologic treatment of obesity and overweight and to define the options with the best risk-benefit using the stochastic analysis of multicriteria acceptability (SMAA). The analysis addresses a systematic review (PROSPERO CRD42023423308) whose research was realized in PubMed, Scopus, and Web of Science. Randomized controlled trials were included, which verified the effects of sibutramine, orlistat, liraglutide, and semaglutide in patients with IMC ≥ 26 Kg/ m². The risk of bias analysis was performed with RoB 2.0 and the outcomes evaluated were weight loss and serious adverse events. A total of 102 studies with 45.047 participants were included. The network meta-analysis revealed that all the treatments were significantly more effective than the placebo in weight reduction. The use of semaglutide (especially 0.4 mg/day) was associated with a bigger weight loss in comparison to all the other treatments (p<0.05) and the analysis of SMAA showed a risk-benefit of 95%. Besides that, we suggest re-evaluating of sibutramine 10mg/day as a therapeutic option for patients without hypertension or cardiovascular diseases, and we demonstrate the modest weight loss promoted by orlistat 120mg, sibutramine 5mg, and liraglutide 1,8mg and advise against its use, once the benefits do not outweigh the risks.

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Abstract This study aims to analyze the existence of information about deprescription in the leaflets of proton pump inhibitor (PPI) medications. The leaflets available on the Brazilian Health Regulatory Agency (ANVISA) and Food and Drug Administration (FDA) websites for the following medications were analyzed: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. The variables collected in each leaflet were the existence: a) about deprescribing; b) of guidance on the deprescription process; c) maximum recommended time for use; and d) risk of prolonged use. This information was analyzed in accordance with the PPI deprescription guideline, from Canada. Regarding the medication leaflets, 83.33 % from ANVISA and 100 % from the FDA did not present explicit and systematic guidance on deprescribing. Regarding the maximum time of use, 100 % of the leaflets from both agencies contained this information. Regarding the risks of prolonged use of the medication, 33.33 % of the ANVISA leaflets and 33.3 % of the FDA leaflets did not report the increased risks described in the guideline. The results highlight a large gap in information about deprescribing in PPI leaflets; this highlighting is necessary to contribute to the promotion of the rational use of medicines.

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Abstract Pharmaceutical controlled-release formulations are systems developed by a set of unit operations to achieve a satisfactory combination between a drug and excipients to allow its gradual release. These devices must simultaneously meet criteria for stability, biocompatibility, safety, efficacy, scalability at industrial volumes, and technological efficiency for drug release. Controlled-release systems (CRSs) must release drugs in a way that maintains an adequate concentration in the organism, a requirement that is challenging to meet in practice. Even though novel CRSs may be designed with new materials as excipients, new drugs, or emerging manufacturing technologies, the mechanisms for drug release continue to be governed by a set of similar physicochemical phenomena such as diffusion, swelling, or erosion. These phenomena are too complex to be analyzed by numerical methods; however, they are relatively accessible by probabilistic models especially the Monte Carlo simulation. In this review, we discuss key findings related to the use of this probabilistic method for analyzing the drug-controlled release process in different pharmaceutical devices. Based on this evidence, we propose their potential application in the characterization of new drug-controlled release systems, synergy with other computational methods, and their capability to be adapted for in vivo or in vitro kinetic analysis.

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Abstract 3D printing, a newer manufacturing technology, is gaining prominence in the pharmaceutical and healthcare sectors, particularly ENT implants. It enables the production of customized biological tissue scaffolds, portable models, and surgical training aids. The emergence of 4D printing offers the potential for enhancing ENT therapy safety and efficacy. The manuscript explores the potential of 3D printing to revolutionize pharmaceutical and clinical practice, enabling the development of personalized drug formulations, patient-centric implants, and anatomical models. This review delves into the emerging concept of “smart” biomaterials used in 4D printing, which are capable of mimicking natural tissues and responding to external stimuli. This paves the way for significant advancements in ENT tissue engineering with the potential to increase treatment safety and efficacy. This highlights the importance of healthcare staff in translating 3D printing innovations into clinical practice for successful adoption. The manuscript highlights the transformative impact of 3D printing in the pharmaceutical and healthcare industries. 3D printing and bioprinting technologies are revolutionizing ENT therapy, offering novel avenues for improved patient care and fostering advancements in the healthcare field.

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Abstract The landscape of scientific research in Latin America (LA), particularly in the realms of the Physiologically Based Pharmacokinetic (PBPK) and Physiologically Based Biopharmaceutic models (PBPM), is a mosaic of varied contributions, collaborations, and specializations. This study examines research production in the region using data from the Scopus and PubMed databases collected between 2011 and 2023. Brazil stands out as a prominent country in terms of the quantity of publications. When considering thematic specialization, Colombia cones first as the country with the greatest Relative Specialization Index (RSI), followed by Brazil, Cuba, Uruguay, Mexico, and Argentina. Regarding internationalization, Brazil and Mexico are currently exerting significant influence, particularly through their increasing cooperation with the United States and Europe. Interestingly, there is a lack of cooperation inside Latin America at the regional level. Regarding the contribution of Latin-American institutions, the State University of Maringá leads in number of publications, followed by the University of São Paulo and the Federal University of São Paulo. In this work, we analyzed the strengths and weaknesses of LA’s scientific contributions, offering a roadmap for future collaborative and specialized efforts in the field of PBPK and PBBM.

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Abstract A significant increase in self-medication was observed during the SARS-CoV-2 pandemic, especially among university students due to their higher level of knowledge and awareness, making them more prone to self-medication. Therefore, in this scoping review we aimed to understand the profile of medications used for self-medication among university students during the pandemic, both for COVID-19 prevention and other reasons. We followed the PRISMA-ScR guidelines in conducting the review. The PICo guiding question was, “What is the profile of medications used for self-medication during the COVID-19 pandemic among university students?” Searches were conducted in the Scielo, PubMed, Embase, EBSCOhost, Web of Science, Scopus, BVS, Google Scholar, and CAPES databases based on MESH and DeCS descriptors. A total of 35 studies were selected, with eight (22.8%) reporting self-medication for COVID-19 prevention/treatment ranging from 14-83%, four (11.4%) reporting self-medication for specific symptoms ranging from 11-95%, 19 (54.4%) reporting several reasons for students self-medicating with a range of 50-100%, and four (11.4%) studies not specifying the reason for medication use in self-medication varying from 3-93%. The included studies revealed that the irrational use of medications is a common practice among university students, with varied prevalence of self-medication observed in this population during the COVID-19 pandemic.

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This study investigates the molecular mechanisms of Rehmannia glutinosa in gastric cancer treatment using network pharmacology, supported by experimental validation. Network pharmacology methods, including active ingredient prescreening, target prediction, gene enrichment analysis, network analysis, and cell-based experiments, were applied to explore the therapeutic action of Rehmannia glutinosa against gastric cancer. Analysis revealed 33 active components and identified 41 potential targets. Gene Ontology analysis indicated that these targets were primarily associated with the biological processes “positive regulation of cell death,” “apoptotic signaling pathway,” and “response to mechanical stimulus.” Kyoto Encyclopedia of Genes and Genomes analysis showed that the targets were enriched in the cancer signaling, prostate cancer, tumor necrosis factor signaling, endocrine resistance-related signaling, and PI3K-Akt signaling pathways. In vitro experiments demonstrated that R. glutinosa total glycosides upregulated Caspase-3 activity, reduced PARP expression levels, and induced cell apoptosis. In conclusion, network pharmacology and experimental results suggest that R. glutinosa may exert its antigastric cancer effects through multiple biological processes and signaling pathways.

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A small subset of cervical cancers tests negative for human Papillomavirus (HPV) DNA, being associated with poorer prognosis and higher aggressiveness. This study systematically reviewed the current status of HPV DNA-independent cervical cancers from clinical, diagnostic and prognostic perspectives, in comparison to HPV-associated cervical cancers. Relevant terms were searchedin databases including PubMed, EMBASE, LILACS, Web of Science, Scopus, CINAHL and the Cochrane Controlled Trials Registered between January 2018 and December 2023. We focused on studies published in peer-reviewed English-language with available abstracts. Researchers independently screened the titles and abstracts and the selected articles were then read in full text. After reaching a consensus, 31 papers were selected for data extraction. Various techniques were employed for HPV testing, primarily based on polymerase chain reaction (PCR) and different types of clinical samples were analyzed. A total of 9.2% of the cases were found to be HPV-negative (mean age of 55.8 years). HPV-independent cervical cancers exhibit distinct characteristics; however, several challenges in interpreting the data were identified. Our findings demonstrate the difficulty in distinguishing truly HPV-independent cervical cancers from false-negative ones. Moreover, there is a critical need for new, more comprehensive and rigorously controlled studies to better elucidate the complexities surrounding HPV-independent cervical cancers.