Abstract in English:

Recombinant immunotoxins (RITs) are considered tumor-specific therapeutics because their variable antibody fragment can specifically bind to target cells, and their engineered toxin fragment specifically kills cancerous cells upon internalization. Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor that is overexpressed in breast cancer (BC) patients and can be used for targeted therapies in the form of immunotoxins. The current study aimed to develop pertuzumab gelonin as a targeted immunotoxin for HER2-positive breast cancer cells using bioinformatics methods and to analyze its properties in silico. The Fab light and heavy chain of pertuzumab were linked to gelonin's ribosome-inactivating region (RIP) region. The amino acid sequence of the antibody chains was obtained from the Protein Data Bank Server (PDB), and the sequence of the RIP region of gelonin was obtained from the National Center for Biotechnology Information (NCBI). The immunotoxin's physicochemical properties, secondary, tertiary, and 3D structure, mRNA folding, allergenicity, solubility, and antigenicity were predicted from online servers, and protein-protein docking was also performed. The immunotoxin is stable, non-allergenic, and binds to HER2 receptors with high affinity. Based on our findings, it can be a good targeted therapy for HER2 breast cancer.

Abstract in English:

Paclitaxel (PTX) and cisplatin (CDDP) are potent cytotoxic drugs that target distinct intracellular pathways employed together for breast cancer therapy. While studies indicate enhanced treatment efficacy with drug combinations, the concomitant rise in adverse effects remains a concern. This study assessed the potential of co-administration of these drugs encapsulated into pH-sensitive liposomes (SpHL) against a murine triple-negative breast cancer model. The cytotoxicity studies revealed a concentration-dependent relationship between drug concentration and cell viability for both drugs. The combination effect of free drugs at IC50 and IC50x2 showed an additive effect, while co-treatment with SpHL-PTX:SpHL-CDDP at IC50x4 (1:3 molar ratio) displayed strong synergism (CI = 0.52). Other combinations exhibited antagonism (CI > 2.0). In vivo studies were performed at PTX:CDDP 1:3 molar ratio in two regimen protocols: single or dual dose protocol, resulting in different cumulative doses. Tumor growth was significantly decreased when two doses of free or encapsulated drugs were used compared to single-dose administration. Notably, encapsulated dual-dose treatments demonstrated enhanced antitumor efficacy, diminished systemic toxicity, and zero mortality. In conclusion, our study underscores the promising potential of co-administering encapsulated drugs into SpHL, highlighting their superior efficacy and reduced toxicity in breast cancer treatment compared to free drugs.

Abstract in English:

The aim of the present study was to obtain a symbiotic drink of a non-dairy matrix based on yacon juice fermented by kefir grains, biomonitored by antioxidant activity and pH value. A Box-Behnken experimental design was carried out to evaluate the effects of the concentrations of yacon juice and kefir grains, as well as of the fermentation temperature, on the antioxidant activity and pH. Thus, it was possible to define the optimal concentrations and temperature for the production of the drink with the best profile. Subsequently, in vitro analyses were performed to evaluate the physical-chemical and microbiological characteristics of the drink, in addition to the in vivo assay using the experimental model Caenorhabditis elegans to assess a possible degree of acute toxicity. The results showed that the drink made with 82.7% yacon juice, fermented with 2% kefir grains at a temperature of 35ºC presented antioxidant potential, increased phenolic compounds, adequate physical-chemical characteristics and chemical composition, and the presence of probiotic microorganisms, in addition to not presenting acute toxicity in vivo.

Abstract in English:

In Brazil, when not criminalized, premature interruption of pregnancy may be performed through surgical abortion procedures (SAP) or medical abortion (MA). In the latter case, misoprostol monotherapy is the only available option, although the MifeMiso combination, which entails misoprostol administration after pretreatment with mifepristone, is the World Health Organization’s (WHO) preferred method. Here, we provide a state-of-the-art literature review, an evaluation of Brazilian clinical protocols, and a data analysis methodology exemplifying the impacts of adopting MifeMiso over misoprostol-only. The combination stands out for its superior efficacy, acceptability, and cost-effectiveness. Our findings show that the Brazilian technical standard could be improved, and that it would be valuable to have mifepristone approved for MA in the country. While legalization of abortion seems distant for Brazil, discussing all aspects of abortion is crucial for proper management of health resources, since the health system already bears the costs of illegal abortion.

Abstract in English:

Human immunodeficiency virus (HIV) is a significant health issue globally and affects millions of people worldwide each year. The infection is treated using antiretroviral therapy (ART) and considered as standard treatment for HIV. The therapy consists of a combination of medicines that slow down or suppress the replication of the virus. Although ART therapy has been successful in managing HIV infection it is not the cure and requires life-long adherence to remain effective. Hence scientists and health workers around the globe are looking for more effective therapy that eliminates the virus from the patient body. Genomic medicine is one of the most significant therapies among these novel treatment procedures. The current advances in genomic medicine and genetic engineering, especially the discovery of CRISPR/Cas9 offer new hope to fight against HIV. In this study, we investigate the current advances in CRIPSR/Cas9 base therapy against HIV. Further, the basics of CRISPR/Cas9 technology, its application in HIV research, challenges, and future perspectives were also investigated.

Abstract in English:

Inflammation is a condition in which the body’s immune system is compromised. Polysaccharides from Mesona chinensis Benth have been shown to repair the immune system and inhibit inflammation. This study aimed to investigate the activities, network pharmacology, and potential mechanisms of action against inflammation of a homogeneous polysaccharide, MCP-1, from M. chinensis. MCP-1 was isolated and purified using water extraction, alcohol precipitation, the Sevag method, and column chromatography. The molecular weight of MCP-1 was determined to be 70.9kDa. The polysaccharide composition included glucose (39.05%), arabinose (18.31%), galactose (14.80%), galacturonic acid (13.98%), xylose (7.42%), mannose (4.14%), and glucuronic acid (2.30%). MCP-1 showed strong inhibitory effects on the release of NO, IL-6, and TNF-α (30.79 ± 4.13%, 30.51 ± 3.25%, and 37.25 ± 3.57%, respectively). A total of 169 targets were identified based on the monosaccharide structures of MCP-1, with 9 targets associated with inflammation, including TLR4, STAT3, MMP9, COL18A1, TLR9, ABCB1, PPARA, MMP2, and NR1H4. The principal targets for anti-inflammatory therapies were associated with various signaling pathways involved in cancer and immune responses. Molecular docking experiments revealed that MCP-1 exhibited a high binding affinity for MMP2.

Abstract in English:

Atopic dermatitis is a chronic skin condition characterized by impaired barrier function and underlying inflammation. Monoterpenes, a diverse class of secondary metabolites commonly found in essential oils, have been extensively documented for their potent anti-inflammatory properties. Therefore, this study evaluated the effects of gamma-terpinene (GT) on dinitrochlorobenzene (DNCB)-induced atopic dermatitis in a murine model. Macroscopic and histopathological analyses were conducted to assess skin lesions and ear edema, along with the assessment of serum immunoglobulin E (IgE), lactate dehydrogenase (LDH), and inflammatory cytokines (IL-4, IL-6, IL-1β, and TNF-α) in skin tissues. Histopathological analysis revealed a reduction in skin thickness, spongiosis, inflammatory cell infiltration, along with the presence of blisters and vesicles in both the epidermis and dermis. Additionally, cellular disarrangement and dermal fibrosis were observed. GT significantly decreased ear edema, serum IgE, and LDH levels, along with the expression of tissue IL-4, IL-6, IL-1β, and TNF-α. Therefore, the potential anti-inflammatory response induced by GT in atopic dermatitis suggests its potential for the development of GT-based therapies for chronic inflammatory skin disorders.

Abstract in English:

Biocatalysis is always considered as an efficient alternative for preparing a wide range of compounds with pharmaceutical/industrial importance. The immense popularity of biocatalysts is due to its striking features of being an environmentally benign, renewable and sustainable.In this present review, different methods of preparation of alcohols from their respective carbonyl compounds using different plant cells as biocatalysts are discussed. In addition, the importance of these alcohols in pharmaceutical industries and their methods of preparation in optically as well as chemically pure form are also discussed.

Abstract in English:

Gene therapy holds substantial promise for the treatment of a wide range of genetic and acquired diseases. Despite its potential, efficient and safe delivery of therapeutic genes into target cells remains a significant challenge. Lipoplexes, lipid-base formulations complexed with nucleic acids, have emerged as an attractive non-viral vector for gene delivery due to their ability to encapsulate and protect nucleic acids and facilitate their delivery into cells. This review focuses on the design, mechanism of action, and structure of lipoplexes for gene therapy and discusses the role of various lipids used in the formation of lipoplexes. Furthermore, we explore the application of lipoplexes in various disease models, cystic fibrosis, and cancers, highlighting recent advances. We conclude that while challenges remain, lipoplexes represent a promising strategy for safe and effective gene therapy.

Abstract in English:

Alzheimer’s Disease is a prevalent form of dementia typically characterized by neurodegeneration, memory loss and cognition loss. Celastrus paniculatus (malkangani) is a well-known brain tonic in Ayurveda, while Grewia asiatica (phalsa) is reported to improve memory and cognition. This study was focused on the development and evaluation of a combined microemulsion of phalsa extract and malkangani oil. The microemulsion was prepared using the water titration method and optimized using Box Behnken Design. The optimized formulation showed particle size of 14.91±0.20 nm, 0.323±0.03 polydispersity index (PDI) and % transmittance of 96.31±0.04 %. The in-vitro drug release was estimated by media change method in 0.1 N HCl and phosphate buffer (pH 6.8) and it found to follow Higuchi order kinetics with about 90 % release up to 8 hrs. Microemulsion significantly improved inflexion ratio in elevated plus maze test; indicating improvement in learning, memory and recognition in scopolamine-induced amnesia in rat as compared to single treatment of oil or extract, however statistically non-significant effect was seen in novel object recognition test. The biochemical tests and histopathological examinations of rat brains also showed the effect of microemulsion when compared to the disease control group. This combination in microemulsion can be used as a prophylactic treatment to prevent neurodegeneration.

Abstract in English:

Pulmonary arterial hypertension (PAH) is a severe disease responsible for high mortality in the affected population. Due to the limitations in treatment as severe adverse effects, high cost, we aimed to develop a simple therapeutic option for pulmonary administration, using a vasodilator sildenafil citrate (SILC) in a dry powder inhalation using lactose as carrier. A formulation of micronized SILC was prepared after 30 min wet grinding of the active with the aid of a vibration shear-mill. Solid characterization by laser diffraction and X-ray powder diffraction was assessed for active. Performance tests such as delivered-dose uniformity (DDU) and aerodynamic particle size distribution (APSD), using Dosage Unit Sampling Apparatus and Andersen Cascate Impactor, respectively, were performed. The micronization of SILC resulted in a medium size of 4.54 μm and a 50th percentile of 2.93 μm. For DDU, the total amount delivered ranged from 92.42 to 109.05% of the targeted dose, in agreement with the specified range (75.0-125.0%). For ASPD, a fine particle fraction of 35% was satisfactorily obtained. This formulation is simple and promising therapeutic option for the treatment of PAH with the advantage of being easily produced using less complex carrier matrix or equipment, in a short time.

Abstract in English:

Leishmaniasis is an underfunded neglected disease that affects 12 million people mainly living in developing countries. Herein, based on the data we obtained in our previous study, we designed and synthesized novel thiazolo[5,4-d]pyrimidine derivatives and evaluated their in vitro antileishmanial bio-activity. The compounds were synthesized, and their structures were elucidated. Then, their anti-leishmanial activities were tested using both promastigote and amastigote-like forms of L. tropica and L. infantum parasites. Additionally, we evaluated the in silico physicochemical properties and the structure-activity relationships of the compounds. Compound 4-chloro-N-[5-(4-hydroxypiperidin-1-yl)miazolo[5,4-d]pyrimidin-2-yl]benzamide (A1), with IC50 values of 43.58 μΜ and 41.45 μΜ against L. tropica and L. infantum promastigotes, respectively, and 70.02 μΜ and 77.13 μΜ against L. tropica and L. infantum axenic amastigote-like forms, was found to be the most active compound in both assays. Compound A1 also exhibited the lowest iLogP value among the compounds, suggesting high passive gastrointestinal absorption. Based on both in vitro assays and in silico properties, compound A1 demonstrates significant anti-parasitic activity and serves as a promising lead for the development of new antileishmanial agents.

Abstract in English:

Adverse drug events (ADEs), such as drug-related bleeding (DRB), represent a serious public health issue and highlight the role of triggers in pharmacovigilance. This study aimed to identify the triggers used to detect inpatient DRB. A systematic review was conducted and registered in PROSPERO (CRD42023440337). The search included the databases PubMed, LILACS, Cochrane Library, Embase, and Web of Science, covering published studies on ADEs in hospitalized adults focused on DRB triggers, with no language restrictions, up to September 2024. Methodological quality was assessed using the Joanna Briggs Institute tool, and trigger performance was evaluated by Positive Predictive Value (PPV). Twenty-three studies were included, identifying 28 triggers for DRB with PPV ranging from 0% to 100%. Prolonged INR and PTT were the most high-performing laboratory triggers, while textual triggers have demonstrated their potential, despite requiring adjustments to avoid false positives. A multimodal approach of laboratory and textual triggers combined emerges as beneficial to ADEs surveillance. Standardized and rigorous methodologies are recommended to strengthen evidence and guide clinical interventions.

Abstract in English:

Acute lung injury (ALI) is a severe disease that can cause extensive lung damage and lead to death. Elevated levels of inflammatory cytokines and associated inflammation and oxidative damage irreversibly damage the lung tissue, leading to death. This study aimed to utilize the powerful antioxidant properties of bromelain (BRO) in ALI to determine its beneficial effects. We used an LPS-induced ALI model in rats, and 40 male specimens were divided into five groups: Healthy, Healthy+100BRO, ALI, ALI + 50BRO, and ALI + 100BRO. At the end of the study, histopathological and biochemical analyses of the lung tissue samples were performed. The results showed that tumor necrosis factor, interleukin-1, interleukin-6, and malondialdehyde levels increased in the ALI group and that these levels decreased dose-dependently with BRO treatment. We also demonstrated that superoxide dismutase levels, which decreased in the ALI group, increased dose-dependently in the BRO treatment groups. Histopathologically, significant improvement was detected in the BRO treatment groups. As a result of this research, it is suggested that BRO should be considered as supportive therapy in ALI. However, more detailed experimental and clinical studies on this subject are needed.

Abstract in English:

Peptic ulcer is a common disease in gastroenterology clinics. This study aimed to investigate the chemical composition, antiulcer, and antioxidant activities of methanol extract of Dioscorea praehensilis rhizomes. The rhizomes were extracted by macerating in 80% methanol and subjected to chemical profiling using Gas Chromatography-Mass Spectrometry (GC-MS). The assessment of anti-ulcer activity was done using ethanol and indomethacin-induced gastric ulcer models in rats while the antioxidant studies were conducted using quantitative analysis of phenolic (total phenols and total flavonoid) compounds, 1,1-diphenyl-2-picrylhydrazyl (DPPH), total antioxidant capacity (TAC) and ferric ion reducing antioxidant power (FRAP) assays. D. praehensilis extracts at 125, 250, and 500 mg/kg ‘per os’ (PO) exhibited a significant (p<0.01) dose-dependent decrease in gastric lesions with the percentage inhibition of 65.16, 68.20, and 79.64% respectively in the ethanol model and 81.89, 90.44, and 95.35% in the indomethacin model compared with the control group. D. praehensilis extract contained high phenolic and flavonoid content. The extract also showed considerable antioxidant activity in the DPPH, TAC and FRAP assays. Furthermore, D. praehensilis contains bioactive constituents such as Pentadecanoic acid, 9-Eicosene, n-Hexadecanoic acid, 4-tert-butylphenol and Pentacosane. In conclusion, D. praehensilis possesses antiulcer and antioxidant activity, supporting its traditional use in treating ulcers and dyspepsia.

Abstract in English:

Validate and compare three prescription-related incident prediction instruments (Matrix-INI, IMEPAG-group, MERIS) in hospitalized patients with infectious disease. Observational follow-up (cohort) study enrolling adults from June 2019 to March 2020, with no prior care from the clinical pharmacist. Matrix-INI, MERIS, and IMEPAG-group instruments assessing preventable drug-related incidents (PDRI) were applied at ward admission and once a week. The outcome of interest was clinically relevant PDRI. For every participant at every time of analysis, the instruments scores were retrieved, and validation was estimated through calibration (slope, intercept), discrimination indexes, and reclassification indexes. 219 patients were screened, and 212 were included. PDRI affected 78.77% of participants. “Anticoagulants” was the strongest predictor. Discrimination of all instruments was always low. (area under ROC curve < 0.70); and weekly performance was insufficient. No reclassification improvement was observed. Matrix-INI, IMEPAG-group assigned lower risks despite PDRI. Discrimination increases slightly every week, with a corresponding calibration loss. Models lacked sufficient predictive performance, pointing to a need for a specific PDRI prediction tool for this population. Empirically developed instruments, such as Matrix-INI, often exhibit poor performance. Regular risk assessments during hospitalization are crucial for dynamic prioritization in clinical pharmacy, as PDRI risk may change over time.

Abstract in English:

Irinotecan (IRO), a potential drug approved by the USFDA used in colorectal cancer, hinders its therapeutic applications due to low solubility and very poor bioavailability. The current research aims to use Dextran sulphate (DEX) nanobubbles (NBs) as a delivery system for IRO to improve the bioavailability and enhance its beneficial effect. Using emulsification technique we formulated IRO-loaded dextran sulphate NBs and optimized utilizing a Box Behnken design with input of process and formulation parameters. The characterization of NBs checked for particle size, drug loading, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffraction studies, and also stability studies, in vitro and in-vivo studies on rats. The optimized NBs presented 89.8 ± 9.5 nm of particle size, -18.6 ± 1.2 mV of zeta potential, and 0.284 ± 0.108 of polydispersity index. NBs showed 72.86 ± 1.54% of entrapment efficiency and 33.57 ± 2.10% of drug loading, while in vitro study showed that ultrasound enhanced the release of drugs by 99%, compared to plain drug, which was only 35%. Characterization studies confirmed the absence of drug-polymer interaction. In conclusion, the findings of this study suggested that this type of formulation might be an alternative for cancer treatment.

Abstract in English:

The work investigated the presence of phytochemicals and antihyperlipidemic potential of the ethanolic extract of Crateva religiosa (CRETE). The extraction yield was found to be highest with ethanol (15.81% w/w), followed by ethyl acetate (11.98% w/w) and very poor in hexane (3.05% w/w), using as solvents of variable polarity. Quantitative phytochemical analysis revealed that CRETE consists of higher total phenolic content (81.19 µg/mg equivalent to gallic acid) and flavonoid contents (49.0 µg/mg quercetin equivalents) compared to the ethyl acetate extract. GC-MS analysis confirmed the presence of stigmasterol, gamma-sitosterol and lupeol as phytochemicals. In vivo studies demonstrated that 400 mg/kg of CRETE reduced the levels of triglycerides (155.9 ± 1.51 mg/dl), total cholesterol (234.27 ± 1.91 mg/dl) and low-density lipoprotein cholesterol (66.27 ± 2.07 mg/dl), while increased the level of high-density lipoprotein cholesterol (133.48 ± 3.72 mg/dl). Atherogenic indices were also improved significantly. CRETE restored hepatic architecture and reduced adipocyte size. CRETE also exhibited strong antioxidant effects by lowering malondialdehyde (MDA) levels and enhancing glutathione (GSH), superoxide dismutase (SOD) and catalase activities. Mechanistically, in comparison to control groups, CRETE inhibited HMG-CoA reductase activity (p < 0.0001) and up-regulated PPARγ (p < 0.01) and CCAAT/EBPα (p <0.05) expressions in adipocytes significantly.

Abstract in English:

Research on anxiety and its treatment among HIV-infected individuals is limited, despite its high prevalence. HIV-positive patients often consume many anxiolytic/hypnotic medications. Pharmacotherapeutic monitoring and multidisciplinary pharmaceutical intervention can improve treatment adequacy, health education, detection of inappropriate prescriptions, drug interactions, patient satisfaction, reduce morbidity and mortality and general health care costs. The objective of the study was to evaluate the impact of pharmacotherapeutic monitoring on the rational use of anxiolytics/hypnotics in HIV-positive patients on antiretroviral therapy. Three pharmaceutical consultations were carried out according to the Dáder method, using the STAI (State/Trait Anxiety Inventory) to assess anxiety levels, and pharmaceutical interventions were carried out. In the first pharmaceutical consultation, all patients presented severe anxiety. In the third consultation, the average was statistically lower in the two anxiety conditions evaluated. In the group of patients where health problems were resolved or partially resolved there was a lower level of anxiety, suggesting that the resolution of health problems through pharmaceutical interventions promoted a reduction in anxiety. It was concluded that pharmaceutical assistance provided through health education integrated with pharmacotherapeutic monitoring using the Dáder Method has a positive impact on the rational use of anxiolytics/hypnotics in HIV-positive patients on antiretroviral therapy.

Abstract in English:

Herbal medicines (HM), derived from whole plants or their parts, play a crucial role in primary health care, with approximately Eighty percent of the global population relying on them. The World Health Organization (WHO) is tasked with establishing guidelines for their use, safety, and quality. Despite these standards, risks associated with self-dosing and variability in regulatory frameworks persist. Regulatory approaches differ worldwide, including Brazilian legislation through ANVISA, Indian regulations under the Drugs and Cosmetics Act, the European Medicines Agency (EMA), and the US Food and Drug Administration (FDA). Each framework enforces high standards for quality, safety, and efficacy, involving rigorous testing on human subjects. While significant strides have been made in standardization and therapeutic consistency, challenges remain. Integrating international standards aims to address these issues, focusing on reducing the risks associated with unsafe and ineffective herbal medicines for consumers. Our review tries to reflect on the various herbal regulations across Brazil, India, European Union, and USA and bring out a comparative opinion on various aspects as well as the need for harmonization of these regulations.

Abstract in English:

This study evaluated the effects of copaiba oil on the kidneys of rats with cirrhosis induced by thioacetamide. Male Wistar rats were divided into four groups (n = 8), namely Control (C), Thioacetamide (TAA), Copaiba Oil (OC), and Thioacetamide + Copaiba Oil (TAA+OC). The biochemical and immunological analyses were performed, and results for the antioxidant enzymatic analysis revealed an increase in GST activity for TAA and TAA+OC compared to C. For GSH, higher values were observed in the TAA and TAA+OC groups compared to the C, but the latter differed from OC, such as TBARS. For Vit C, the TAA+OC group differed from the C and TAA and for glucose and lactate, lower values were observed for the TAA+OC group compared to the OC group. Cytokine concentrations showed the same profile with the TAA+OC group showing lower values compared to the C and OC groups. The data obtained do not show a clear positive effect of copaiba oil on kidney tissue when compared to the potential damage caused by thioacetamide. However, the groups that received either thioacetamide or copaiba oil alone maintained their basal levels, indicating that, at the doses used, these compounds did not negatively alter renal morphology.

Abstract in English:

Paclitaxel (PTX) is a widely used anti-tumor drug in cancer therapy. However, its poor water solubility restricts its application in therapeutic procedures. Furthermore, the Cremophor® in the formulation can cause various side effects, leading to non-specific drug distribution in tumors and normal tissues. To overcome these limitations, researchers have explored numerous drug delivery systems to enhance the solubility of PTX and achieve targeted delivery. One such strategy involves using polymer nanoparticles, tiny particles composed of polymers that encapsulate and stabilize PTX, thereby improving its solubility and bioavailability. In addition, these polymer nanoparticles can enhance the therapeutic effect of PTX through passive targeting and active targeting mechanisms. This review first highlights the challenges of paclitaxel in current applications, focusing on current synthetic advances in PTX and drug resistance; subsequently, various approaches to deliver PTX using polymer Nanoparticles are discussed. Finally, current challenges and prospects are reviewed. Our goal was to demonstrate how these different nanocarriers can improve the therapeutic efficiency of PTX as a chemotherapeutic agent.

Abstract in English:

Metformin HCL (MET-HCL), is a Biguanide derivative, most effective agent in treatment of PCOS. The focus of the present study was on developing and optimizing a nanoemulsion formulation. of MET-HCL and convert into intravaginal MET-HCL Nanoemulsion Gel (MET-HCLNE GEL) To enhance the therapeutic efficacy in managing PCOS. The nanoemulsion was formulated using water titration method and evaluated for droplet size, zeta potential, polydispersity index (PDI), drug content, viscosity, and morphology. Then incorporated into gel and evaluated for pH, drug content, viscosity, in-vitro release & in-vivo study. The formulation MET-HCLNE 1 showed the desired droplet size (45.60 ± 1.7 nm), PDI (0.198 ± 0.2), zeta potential (22.4 ± 0.3), drug content (89.19 ± 0.2 %) and viscosity (42.85 ± 2.1 cp). In in-vitro release, MET-HCLNEGEL showed significant prolonged release over MET-HCL solution. Intravaginal MET-HCLNE GEL showed significant efficiency against PCOS compared to oral administration in female Wistar rats. No significant changes were found in the values of viscosity, drug content and pH over the period of 120 days. Thus, MET-HCLNE GEL was found to have good potential to function as an Intravaginal formulation & having great PCOS activity and good storage stability.

Abstract in English:

A study was conducted to create drug utilization evaluation (DUE) standards for ceftazidime-avibactam (CZA) and evaluate CZA use at the First Affiliated Hospital of Bengbu Medical University, China, from May 26, 2020, to December 18, 2024. First, we organized an expert panel and created DUE standards for CZA. Then, we performed an observational study and evaluated the physician CZA prescribing behaviors, which were compared to the DUE standards and calculated the compliance rates. The DUE CZA standards had medication indications, management metrics, administration process, and treatment outcomes. Sixty-four patients received the CZA during the study period. There was satisfactory compliance between CZA prescription and DUE standards regarding route, solvent, incompatibility, and contraindications. However, the compliance rates for CZA indication, dosage regimen, infusion time, combination therapy, drug interaction, and duration of treatment were 68.8% (44/64), 65.6% (42/64), 29.7% (19/64), 73.3% (44/60), 43.8% (28/64), and 62.5% (40/64), respectively. The pre-CZA bacteria culture test was 96.9% (62/64). In addition, medical records and prescription authorization were 95.3% (61/64) and 71.9% (46/64) compliant, respectively. No adverse reactions were reported. In conclusion, the CZA DUE standards could be applied to identify inappropriate prescriptions for improvements.

Abstract in English:

Bacteriophages, which infect bacterial cells, have a unique ability to reduce bacterial colonization, particularly in antibiotic-resistant biofilm infections. This study aims to fabricate optimized bacteriophage-loaded nanofibers composed of polyvinyl alcohol (PVA) and hyaluronic acid (HA) using machine learning techniques. A comparative analysis was conducted to determine the most efficient machine learning algorithm for this purpose. The eXtreme Gradient Boosting (XGBoost) algorithm was used to optimize three sets of bacteriophage-loaded nanofibers-GA1, GA2, and GA3-at varying sonication times. The nanofibers were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), mucoadhesion analysis, thermogravimetric analysis, tensile strength analysis, and a bacteriophage release assay. SEM analysis revealed that GA3 exhibited homogeneous, well-aligned, defect-free polymer fibers with smooth surfaces, whereas GA1 and GA2 contained bead-like structures. Thermal degradation occurred between 300 °C and 368 °C, with GA1 displaying the highest tensile strength. Predicted values for mucin adsorption and bacteriophage release closely aligned with experimental data, confirming the accuracy of the XGBoost model. Finally, the release of MDR-specific phage Pɸ-Mi-Pa from the optimized nanofibers was highest at pH 5, which is similar to vaginal pH. These findings highlight the potential of these nanofibers for phage therapy, particularly in improving the prognosis of antibiotic-resistant biofilm infections.

Abstract in English:

A novel LC-MS/MS method was developed and validated for the simultaneous quantification of venetoclax and obinutuzumab in rat plasma and successfully applied to pharmacokinetic investigations in male wistar rats. Chromatography was performed on a Symmetry C18 column (150 x 4.6 mm, 3.5 µm) column utilizing multiple-reaction monitoring (MRM) mode to evaluate venetoclax, obinutuzumab, and the internal standard gossypol, following which they were extracted using liquid-liquid extraction. The assay demonstrated high sensitivity, excellent reproducibility, and full compliance with FDA bioanalytical validation criteria, with venetoclax exhibiting a linear range of 25-200 ng/mL and obinutuzumab 6.25-50 ng/mL, respectively. The high-abundant mass transitions were seen starting from 869.4425 and 603.8597 m/z for venetoclax and 146.5948 and 67.6239 m/z for obinutuzumab and Gossypol (IS) 519.5638 and 206.7486 m/z, respectively. Upon application, the study successfully characterized the pharmacokinetic profiles of venetoclax and obinutuzumab in Wistar rats, revealing differences in absorption and systemic exposure between the two compounds. Venetoclax demonstrated a higher Cmax and AUC with a delayed Tmax compared to obinutuzumab, although both shared a similar elimination half-life of 20 hours. The results indicate consistent and stable pharmacokinetic behaviour under the tested conditions, supporting future therapeutic drug monitoring and preclinical drug development.

Abstract in English:

This study was conducted to explore the mechanism of Sea Buckthorn Granules (SBG) in treating chronic bronchitis (CB) in rats. The primary chemical components of SBG were identified using UPLC-Q-TOF-MS/MS. A rat model of CB was established through smoke inhalation combined with lipopolysaccharide (LPS) stimulation, followed by oral administration of SBG. The serum levels of TNF-α, IL-6, and IL-1β in rats were measured using ELISA. Pathological changes in lung tissues were observed through HE and toluidine blue staining. Furthermore, the main components and pathways involved in the therapeutic effects of SBG on CB were predicted using network pharmacology. In addition, p38 and NF-κBp65 protein expression as well as their phosphorylation levels in rat lung tissues were measured by western blot. Compared to the model group, treatment with SBG significantly alleviated cough symptoms, and Mitigating body weight loss in CB rats (P<0.05). SBG markedly decreased serum levels of TNF-α, IL-6, and IL-1β (P<0.05); as well as reduction in both NF-κBp65 expression levels and p38 phosphorylation within lung tissues (P<0.05). In summary, SBG can effectively ameliorate cough symptoms while reducing serum TNF-α, IL-6, and IL-1β levels, as well as inhibiting the MAPK/NF-κB signaling pathway.

Abstract in English:

Inhalable dry powders containing dextran-behenic acid polymeric micelles (PM) were developed for the local delivery of niclosamide (NCL) to combat bacterial infections in the lungs of patients with cystic fi brosis. NCL loaded PM were prepared using dialysis method. Inhalable nanocomposites loaded with NCL were effectively prepared by co-spray drying the PM with inert carriers like mannitol and lactose. The physicochemical properties and in vitro deposition of the aerosolized nanocomposites were then evaluated. Additionally, the in vitro effi cacy of the prepared formulations against staphylococcus aureus was assessed using the agar well diffusion method. The optimized formulation exhibited a particle size of 333.67 ± 22.36 nm, a polydispersity index of 0.53 ± 0.08, a zeta potential of -2.90 ± 0.18 mV, an encapsulation effi ciency of 52.07 ± 3.88%, a drug loading of 19.94 ± 1.49%, and a release effi ciency of 54.04 ± 3.11%. Scanning electron microscopy also revealed that the nanomicelles were nearly spherical in shape. Both the NCL-loaded nanocomposite and PM demonstrated superior antibacterial effi cacy at higher concentrations, as compared to free NCL and drug-free PM. It can be, therefore, concluded that dry powders embedding NCL-PM may serve as a viable alternative therapy for treating lung infections in patients with cystic fi brosis.

Abstract in English:

With the increase in life expectancy, the demand for pharmaceutical care has risen, with the need to improve drug adherence. The study aimed to evaluate which variables in the literature most influence adherence. Two hundred twenty older patients from a specialty outpatient clinic were included. Potential drug interactions were identified using the Brief Medication Questionnaire (BMQ), and the Cumulative Illness Ratings Scales for Geriatrics and WHOQOL-Bref questionnaires were applied. The mean follow-up time at the outpatient clinic was 7.7 years, with 65% belonging to socioeconomic class C. The mean number of medications in use was 7, and 44% of the participants were taking psychotropic medication; 80.5% showed potential drug interaction. Cluster analysis revealed two groups: those motivated but concerned about their pharmacotherapy, and another with higher scores in drug effects and bothersome features, pain, and fear related to pharmacotherapy. The structural equation model showed that the BMQ total score was dependent on drug interaction and the public healthcare system's supply of medications. The concurrent use of multiple drugs and potential drug interaction favor nonadherence to medication, while adherence increases when the drug is provided by the health system, aspects that should be observed by the pharmaceutical attention to improve the treatment of older people.

Abstract in English:

The objective of this study was to develop, optimize and evaluate Apremilast niosomes integrated into a topical gel for improved skin permeation. Niosomes were prepared by thin film hydration technique using cholesterol and Poloxamer 188. Niosomes optimization was employed using BoxBehnken Design wherein three variables cholesterol concentration, Poloxamer 188 concentration and stirring speeds were studied on responses entrapment efficiency, particle size, drug release, and release kinetics. The optimized niosomes were further evaluated for zeta potential and surface characterization by transmission electron microscopy. The selected niosomes were loaded into Carbopol based gel and evaluated for appearance, pH, rheology, in vitro drug release and ex vivo skin permeation studies on excised rat dorsal skin. The niosomal formulations by BBD design exhibited entrapment efficiencies ranging from 53.43% to 76.36% and particle sizes from 204 nm to 282 nm. Sustained drug release profiles were observed, with drug release percentages between 60.01% and 99.11% after 10h. Based on the opted design space and experimentation, optimization of niosomes by thin film hydration using BBD was achieved. The optimized niosomes were assessed for particle size (274.7 nm), zeta potential (37.6 mV), entrapment efficiency (68.29%), drug release (88.36% after 10h), transmission electron microscopy (uniform distribution with spherical shape) and drug release kinetics showing Korsmeyer-Peppas (non-fickian) model as best fit for drug release. The niosomal gel was formulated with acceptable characteristics for appearance (uniform gel, without phase separation), pH (6.91), viscosity (1498.7 Pa.s) and drug content (96.5%). Similarly, conventional Apremilast gel was also prepared for drug release and skin permeation comparison. The in vitro release experiments indicated consistent and sustained drug release for 6h with 83.5% drug release compared to conventional gel which showed 3h with 97.1% of drug release. Skin permeation studies showed improved deposition of Apremilast with niosomal gel in the skin (1750µg) compared to the conventional gel formulation (731µg), indicating improved skin permeation and deposition of Apremilast in the skin by niosomal drug delivery. The results emphasize the potential of niosomal gel formulations for enhancing topical delivery of Apremilast. The optimized niosomes loaded into topical gel system improved skin permeation and drug deposition with the layers of the skin. These attributes show the potential to improve drug delivery across the skin for poorly permeable drugs. Future research shall focus on in vivo studies to establish efficacy and safety for therapeutic applications.

Abstract in English:

The National Program for the Qualification of the Pharmaceutical Services in the Unified Health System (Qualifar-SUS), established in 2012, aims to contribute to the process of implementation, improvement and systemic integration of Pharmaceutical Services (PS) activities in the municipalities, aiming to continuous, comprehensive care, qualifying management processes for adequate and safe access and use of medicines. This analysis sought to historically contextualize its formulation and expansion design throughout its ten years of execution in Brazilian municipalities. To this end, a documentary analysis was carried out with an essay discussion, organized in the items listed for the formulation of Public Policies. Documents published in the period from 2008 to 2021 by the federal government, organized entities of managers, thematic magazines on management, and reports from auditory sessions of the federal court of accounts were read. With the analysis of these documents, it was possible to visit details of the creation, implementation and execution of government actions in addition to the texts of ordinances, resolutions and published regulations. This analyses made it possible to make notes about the program, its actors and arenas so that they can serve as a tool to strengthen access to medicines in Brazil.

Abstract in English:

This study aimed to determine the chemical composition and biological activities of extracts from commercial samples of Aspidosperma excelsum stem bark. The extracts underwent preliminary phytochemical screening, chromatographic fractionation, and spectrometric and spectroscopic analyses, including mass spectrometry and nuclear magnetic resonance. Antioxidant and antimicrobial activities were also evaluated. Phytochemical screening revealed the presence of alkaloids, anthrones, triterpenes, and steroids. Fractionation led to the isolation and structural identification of the indole alkaloids carapanaubine and O-acetylyohimbine. APCI-MS/MS analysis of the crude extracts identified three additional indole alkaloids: spruceanumine B, 10-methoxydihydrocorinanteol, and 11-methoxy-yohimbine. In antimicrobial assays, the hexane extract exhibited moderate antifungal activity against Candida parapsilosis (MIC = 400 µg/mL), while the other extracts displayed weak activity (MIC = 1600 µg/mL). Against Candida albicans, all extracts demonstrated weak antifungal activity, and none showed antibacterial activity at the tested concentrations. Total phenolic content was low, ranging from 31.25 to 138.06 ± 0.9 mg GAE/g. The hexane extract lacked antioxidant activity, while the chloroform, ethyl acetate, and methanol extracts exhibited relatively high activity in the ABTS•+ assay (801.88 ± 42.22 to 936.33 ± 61.28 μM TE) compared to Trolox (500–1000 μM TE). However, all extracts displayed low activity in the DPPH• assay. These findings suggest that A. excelsum warrants further investigation to explore the antioxidant and antimicrobial properties of its identified constituents.

Abstract in English:

Ilhéus virus (ILHV), an arbovirus belonging to the Flaviviridae family, poses a significant health threat with limited knowledge about its protein structures. This study aims to fill this gap by using structural analysis and molecular dynamics-based pharmacophore modeling. These advanced molecular tools enable us to develop a robust virtual screening model for identifying potential antiviral drugs against ILHV. The present study used the Robetta protein molecular modeling tool (https://robetta.bakerlab.org), molecular dynamics simulations using GROMACS, molecular docking using AutoDock Vina, and the nAPOLI server for analysis of protein-ligand interactions. Our molecular docking results reveal the remarkable affinity of caffeic acid to act like an allosteric inhibitor by binding the NS2B- NS3 protease. This finding is important as the NS2B-NS3 protease has highly conserved domains among Flavivirus, suggesting that caffeic acid could be a pan-flavivirus antiviral drug. Although this research is in silico, it provides insights into essential molecular interactions, paving the way for targeted drug discovery in the fight against ILHV and related arboviruses.

Abstract in English:

Senescence or aging is often associated with onset of morbidities, which have been attributed to the harmful phenomenon of glycation. To date, no drug is available to combat this deleterious process. The drug repurposing is a robust and cost-effective approach to identify potential candidate molecules for drug discovery programs. In present study, Meloxicam (MEL) was evaluated for its capacity to be repurposed against glycation. Using the Fructose-BSA model, the anti-glycation effect was evaluated by measuring intrinsic fluorescence of Advanced Glycation End Products (AGEs). The fructoseamine load and free lysine availability was estimated using NBT and TNBSA assays respectively. The BSA secondary structure was assessed by Thioflavin-T, Congo red and Circular Dichroism tests. Finally, lysine blockade and carbonyl entrapment was evaluated as a possible mode of anti-glycation action. Our data showed that MEL (0.5, 1, and 2mM) has significantly reduced the AGEs formation (IC50 = 0.25mM). The load of fructosamine adducts along with free lysine availability was found to be reduced. The secondary structure of BSA was preserved. Regarding mode of action, MEL did not block lysine residues, which was also supported by computational data. However, it was found to entrap carbonyl intermediates. In conclusion, the present study demonstrate that MEL possess anti-glycation potential, which can be attributed to entrapment of carbonyl intermediates. Hence, MEL, a clinically used NSAIDs, present itself as promising candidate to be repurposed against deleterious phenomenon of glycation.

Abstract in English:

The biosafety of cow’s milk-derived extracellular vesicles (mEVs) has not been fully explored, particularly regarding its potential as an in vivo drug carrier. This study systematically evaluated the biosafety of mEVs by assessing their in vitro cytotoxicity as well as in vivo toxicity, immunogenicity, and potential for irritation in mice. The results showed that mEVs exhibited minimal cytotoxicity in vitro, with no significant effect on cell viability. Furthermore, repeated injections of mEVs did not induce aberrant immune responses, irritation or toxicity in mice, indicating that mEVs are a highly biocompatible and safe drug carrier with promising biomedical applications. However, further research is needed to fully understand their long-term effects and optimize their use.

Abstract in English:

The present study aimed to investigate the chemical composition of essential oils (EOs) and methanol extracts of Orthomnion rostratum and Orthomnion medium species. The EOs were obtained using hydrodistillation (HD) and microwave distillation (MWD) and analyzed by GC-FID-MS. Octanal (24.12%, HD; 20.22%, MWD), pentanal (31.45%, HD), and n-pentanol (25.50%, MWD) were found to be significant compounds, respectively. Analysis of the phenolic constituents of the methanol extracts of O. rostratum and O. medium yielded apigenin glucoside derivatives as the major compounds, with concentrations of 1.355 and 0.382 mg/g, respectively. The antimicrobial activities of the EOs and solvent extracts (n-hexane, chloroform, methanol, and water) of both species were evaluated against nine microorganisms. EOs obtained using MWD from both species exhibited the strongest antimicrobial activity against Staphylococcus aureus (15.9 µg/mL and 15.0 µg/mL), Enterococcus faecalis (31.9 µg/mL and 30.0 µg/mL), Bacillus cereus (15.9 µg/mL and 15.0 µg/mL), respectively.

Abstract in English:

The leaves of Aegle marmelos (AML) and Bryophyllum pinnatum (BPL), and unripe fruit peels of Carica papaya (CPFP) are traditionally used, either alone or in combination, to treat inflammatory conditions, without substantial scientific evidence. Therefore, this study aimed to investigate their phytochemical constituents and anti-inflammatory activities. Petroleum ether, chloroform, and methanol extracts were prepared by sequential extraction and subjected to qualitative and quantitative phytochemical analyses. The extracts were screened for in vitro free radical scavenging and anti-inflammatory activities. The extracts showing higher activities were tested at 125, 250, and 500 mg/ kg doses for anti-inflammatory activity using carrageenan-, CFA-, and potassium oxonate-induced inflammation models. The three plants’ methanol extracts showed comparatively higher flavonoids, polyphenols, and glycosaponins contents. The same extracts showed higher antioxidant and anti-inflammatory activities (p < 0.05). The anti-inflammatory activity was dose-dependent, along with restoration of morphology and histology of the inflamed tissues. The current study’s findings provide chemical composition and evidence for these folklore medicinal plants in treating inflammatory conditions like arthritis and gout. These studies suggest bioassay-guided isolation of these ingredients.

Abstract in English:

It is considered that besides being involved in the etiology and progression of rheumatoid arthritis, oxidative stress (OS) may be increased by medications used in the treatment of autoimmune diseases, such as methotrexate. Therefore, the present study sought to evaluate the oxidative stress biomarkers in patients with rheumatoid arthritis who use methotrexate and associate this medication with adverse reactions and use of other medications. This is a longitudinal, analytical and quantitative study. The sample consisted of 40 patients. The characterization of patients and data on medication use and adverse reactions were collected through a questionnaire. At the same time blood was collected for the analysis of OS biomarkers. Among the most relevant finding, an association between the use of antiemetics and antidepressants and lower SOD and CAT levels was found. It was also observed that CAT, SOD and TBARS levels were higher among those who reported adverse reactions of MTX. In conclusion, controlling side effects is important to minimize damage resulting from treatment. It is therefore important that a pharmacist monitors the treatment so as to reduce risks to patients and the damage that may be caused by uncontrolled and supervised adverse reactions

Abstract in English:

Prostate cancer changes from an androgen-dependent to an independent type during its progression, and metastasis greatly limits treatment options and survival rates. Matrix metalloproteinases (MMPs) play an essential role in inflammation, malignant cell proliferation, invasion, and metastasis by inducing matrix degradation. Endogenous tissue inhibitors of MMPs (TIMPs) limit the activities of MMPs. The integrin signalling regulates cancer cell adhesion, proliferation, and migration by promoting MMP activation. Clinoptilolite is a micronized type of zeolite, which is a hydrated aluminosilicate. It is used as a chelation and detoxification agent to remove heavy metals from the body. This study investigated the effects of clinoptilolite on the expression and/or activity of gelatinases (MMP-2/MMP-9), MMP-14, TIMP-2, and αvβ1 integrin in PC3 cells. PC3 cells were incubated with/without clinoptilolite (25 mg/ml) for 24 h. The expression and/or activity of MMP-2 and MMP-9 were determined by gelatin zymography. The expression levels of MMP-14, TIMP-2, and αvβ1 were examined by immunostaining. Clinoptilolite inhibited MMP-2 activity and MMP-14 expression while up-regulating TIMP-2 expression, and it decreased MMP-2/TIMP-2 and MMP-14/ TIMP-2 ratios, which are critical for MMP/TIMP balance. Clinoptilolite also down-regulated αvβ1 integrin expression. Clinoptilolite may be useful in prostate cancer treatment due to its αvβ1 integrin-mediated MMP inhibitory effects.

Abstract in English:

The high prevalence of vulvovaginal candidiasis necessitates the development of better treatments. This study aimed to develop a novel nanocomposite vaginal suppository incorporating gelatin and clotrimazole-loaded coconut oil nanocapsules. The nanocapsule suspensions, prepared using Eudragit® RS100, achieved a size of under 190 nm, a polydispersity index of below 0.15, nearly 100% drug content and encapsulation efficiency, a positive zeta potential of +8.5 mV, and an acidic pH. The mucoadhesive properties were confirmed through mucin interaction tests. Suppositories were formulated by integrating gelatin and glycerin into the nanocapsule suspension, maintaining the nanometric size at 135 nm and attaining a high drug content of 97.48%. The nanocomposite suppository demonstrated an enhanced control of drug release, with 40% released in 5 hours, in contrast to 80% from the non-nanotechnological formulation. Additionally, drug retention in cow vaginal mucosa was superior with the nanocomposite suppository (11.95 μg/cm2) compared to the non-nanotechnological formulation (8.18 μg/cm2). The dispersion time did not exceed 60 minutes (24.29 ± 1.91 minutes). The washability test confirmed high mucosal retention, evidenced by drug concentrations in the lavage fluid being lower than 5% for both formulations (nanocomposite and control). These results suggest the feasibility of a nanocomposite suppository with desirable characteristics for vaginal drug delivery, representing a promising alternative for the management of vulvovaginal candidiasis.

Abstract in English:

Diltiazem hydrochloride (DH) is a calcium channel blocker used to modify or restore normal heart rhythm in cardiovascular diseases. The aim of this study was to develop and validate a new innovative method using UV molecular absorption spectrophotometry to evaluate the in vitro dissolution of DH using a factorial design of experiments. Physical and physicochemical tests were performed. The dissolution profiles of DH tablets (30 and 60 mg) available as the reference, generic and similar drugs were compared. The dissolution test was used to obtain and compare dissolution profiles and to determine the similarity of pharmaceutical formulations (USP type 2 apparatus at 75 rpm, with 750 mL of water at 37.0 ± 0.5 oC for 120 minutes). Only samples G30 and G60 showed compliance with the parameters established by the Brazilian Pharmacopoeia in all tests. Drug dissolution percentages are in accordance with the Brazilian and American Pharmacopoeias (>75% dissolution in 180 minutes). Using the proposed new method, it was observed that > 80% of DH was released in approximately 60 minutes. The proposed method was found to be sensitive, rapid and efficient for the quality control of DH tablets.

Abstract in English:

The most potent analgesics cause serious Adverse Drug Reactions (ADRs), so medications such as metamizole, viminol, and tapentadol may be alternatives. However, the safety of these analgesics still needs to be better understood. This study aims to assess prospective ADRs associated with these analgesics in a pain clinic. We followed up with the patients who had used these medicines for 45 days, classified the ADRs according to severity (mild, moderate or severe), mechanism (type A or type B), and incidence (very common, common, uncommon, and rare), and determined the causality. Among 240 patients, three ADRs to metamizole, seven to viminol, and 11 to tapentadol alone were documented. Additionally, 22 suspected ADRs were attributed to potential drug interactions among these analgesics and other medications. The ADRs were categorized as mild to moderate, type A, and common or uncommon. Causality was categorized as certain or possible. The ADRs induced by viminol were associated with age, with each year of age leading to a 6% increase in risk of ADRs, according to a logistic regression model applied specifically to this drug. No other association was found between tapentadol or viminol and comorbidities. It was not possible to analyze the metamizole data due to its low incidence. Overall, metamizole was the safest, reinforcing its safety profile and its valuable indication in the treatment of pain.

Abstract in English:

The use of natural ingredients, such as vegetable oils, in hair care products has gained significant attention due to their conditioning and protective properties. This study evaluates the impact of chemical treatments on hair fiber integrity and assesses the effectiveness of conditioners containing jojoba and coconut oils. The investigation employed advanced analytical techniques, including the Dia-stron® MTT175, SAMBA® Hair System, Attension® tensiometer, and Olympus transmitted light microscopy. Sensory analysis was conducted using descriptive and discriminative ranking methods. Results indicated that bleaching followed by dyeing increased combing resistance and friction while reducing shine and hydrophobicity. Conditioners mitigated these effects, except for the jojoba oil formulation, which did not significantly reduce combing resistance. Shine remained unaffected by all conditioners, though formulations with vegetable oils enhanced the water contact angle of hair fibers, indicating improved hydrophobicity. Optical microscopy confirmed that conditioners smoothed the hair cuticles. Sensory evaluation revealed that participants preferred conditioners containing vegetable oils over the base formulation. These findings suggest that incorporating vegetable oils into hair conditioners can enhance hair fiber properties and consumer preference.

Abstract in English:

A series of fused pyrimido[4,5-d]pyridazin-2(1H)-one, pyrimido[3’,4’:3,2]pyrimido[5,4-d]pyridazin-10-one, pyridazino[4’,5’:5,6]pyrimido[2,1-i]purine and pyridazino[4’,5’:4,5]pyrimido[2,3-b]purin-4(5H)-one were designed and prepared by condensation of hydrazine with pyrimidinone dicarboxylic acid esters in methanol as a solvent. The in vitro antioxidant potential of the target compounds and their precursors was demonstrated by applying free radical scavenging assays using 1,1-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS+•) methods. The synthesized compounds 6b and 7b showed the highest antioxidant activity against DPPH with IC50 of 6.55 and 7.93 μg/mL, respectively, compared to ascorbic acid (IC50 = 5.42 μg/ mL). In addition, compounds 5a and 6b showed a greater ABTS radical scavenging effect than BHT (IC50=75.39 μg/mL). The antibacterial activity of the synthesized compounds was evaluated and compared with Gentamicin. Four bacterial strains were considered: Staphylococcus aureus ATCC-6538, Salmonella typhimurium ATCC-14028 (Gram-positive: G+), Pseudomonas aeruginosa ATCC-9027 and Escherichia coli ATCC-8737 (Gram-negative: G-). Compound 4a showed good activity against Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhimurium with inhibition zones of 23, 22 and 21 mm, respectively, compared to gentamicin (23, 25 and 22 mm). These results encourage exploration of new biological evaluations and applications of these compounds.

Abstract in English:

The World Health Organization has listed Snakebite Envenomation as a significantly ignored tropical disease with a worldwide annual snakebite affecting millions of people, especially in Africa. This study evaluated the in vivo and in vitro neutralising effects of the aqueous extract from the aerial parts of Caralluma dalzielii against snake venom. In the in vivo study, 35 Wistar rats were divided into seven groups, receiving snake venom and treatments with plant extract or standard anti-venom. Mortality rates, haematological, and biochemical parameters were recorded. Whereas, in the in vitro study, different concentrations of plant extract were tested for enzyme inhibition against Naja nigricollis venom. The results showed that the plant extract prevented mortality in all treated groups, comparable to standard anti-venom, and exhibited immunostimulatory effects, increasing WBC levels. It also prevented biochemical disturbances caused by venom, with the highest dose (500 mg/kg) maintaining normal liver enzyme levels. The extract at 100 mg/ml achieved 64.29% enzyme inhibition of PLA2, while the standard anti-venom reached 82.63%, showing concentration-dependent inhibition. In conclusion, the aqueous extract of C. dalzielii exhibits significant anti-venom activity both in vivo and in vitro, demonstrating its potential as a therapeutic option for treating snake bites.

Abstract in English:

Toxic and hazardeus substances have negative effects on both the environment and human health. In this study, we aimed to determine the relationship between use of synthetic cannabinoids and complete blood count parameters, neutrophil/ lymphocyte ratio (NLR), platelet/eosinophil ratio (PER) and platelet/lymphocyte ratio (PLR). 104 patients aged 18-65 years were evaluated retrospectively. Patients were divided into 3 groups; in control group (Group 1) no metabolites detected in urine samples, Group2 positive for bonsai and Group3 positive for marijuana metabolites. Neutrophils, NLR and PER were higher, while %lymphocyte and %eosinophil were lower in Group 2 than Group 1 (p<0.05). The NLR of Group 3 were higher whereas %lymphocyte were lower compared to Group 1(p<0.05). The %eosinophil were lower, in contrast PER was higher in Group 2 compared to Group 3 (p<0.05). The findings of our study showed that bonsai consuming decreased lymphocyte percentage, eosinophil percentage while increasing neutrophil percentage, NLR and PER.We also found that marijuana consumption increased neutrophil percentage and NLR, and reduced lymphocyte percentage values. We believe that further research is needed to fully elucidate the effects of cannabinoid use on blood parameters.

Abstract in English:

Increasing numbers of HIV infections have been reported over the last years. Despite the availability of antiretroviral therapy, the emergence of drug-resistant strains and side effects of marketed drugs makes the search for new drugs needed. Herein, we investigated the antiviral potential of 3-acylhydrazone-4-quinolones (compounds 2-4) against HIV-1 replication in MT-2 cells, their mechanism of action, and pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico methods. All compounds showed lower cytotoxicity (CC50 > 700 µM) than the drug zidovudine (CC50 = 128 µM). Compound 2 showed the most potent anti-HIV-1 activity (EC50 = 3.37 µM), followed by compounds 3 (EC50 = 3.79 µM) and 4 (EC50 = 4.03 µM). Mechanistic studies indicated that these compounds act at post-entry steps of virus replication, such as reverse transcription. Enzymatic assays confirmed that compounds 2 and 4 (IC50 = 29.52 µM and 22.77 µM) inhibit HIV-1 reverse transcriptase (RT). Molecular docking with HIV-1 RT showed that compounds 2 and 4, but not 3, share a similar binding mode with the non-nucleoside RT inhibitor delavirdine, explaining their different activity. Further, ADMET studies reinforced their potential as drug candidates which, in turn, support the design of new derivatives as anti-HIV-1 drug candidates.

Abstract in English:

Cecropins are vital innate immune effectors in pathogen defence of animals. Studies have demonstrated that cecropins also possess anticancer capacity against numerous cancerous cells. In this study, the anticancer effects of A. pernyi cecropin D (ApCecD) and cecropin like protein (ApCecL) were investigated in human breast cancer MDA-MB-231 cells. CCK-8 assay indicated that ApCecD and ApCecL suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner. Wound healing experiments showed that A. pernyi cecropins inhibited the migration of MDA-MB-231 cells. Hoechst staining suggested that treatment with ApCecD and ApCecL induced apoptotic features, including nuclear-like chromatin condensation and increased in nuclear body fragments. Western blotting results showed that ApCecD and ApCecL induced apoptosis via mitochondria-mediated endogenous pathway by upregulating the expression of caspase 3, BNIP3 and Bax. These findings indicated that ApCecD and ApCecL are promising candidates for developing new drugs in breast cancer treatment.

Abstract in English:

The brain is particularly vulnerable to oxidative stress, which is associated with neurodegenerative and neuropsychiatric disorders, including anxiety. Antioxidant therapy, particularly with polyphenols and flavonoids, shows promise in mitigating these conditions. This study evaluated the anxiolytic effects of an ethanolic extract of Gerbera jamesonii Adlam flowers (EEGJ) in Swiss albino mice. The anxiolytic activity was assessed using the elevated plus maze, hole board, open field, and light-dark tests, with EEGJ administered at doses of 200-400 mg/kg and compared to buspirone (10 mg/kg). Phytochemical analysis of EEGJ revealed the presence of various bioactive compounds, with total phenolic and flavonoid contents measured at 329.39 mg GAE/g and 635.22 mg RT/g, respectively. EEGJ demonstrated potent antioxidant activity (IC50 = 64.0 µg/mL) similar to ascorbic acid (53.6 µg/ mL). At 400 mg/kg, EEGJ showed significant anxiolytic effects (p < 0.05) across all tests, marked by increased entries and time spent in open arms of the elevated plus maze and significant results in other behavioural tests. These results indicate that EEGJ has notable anxiolytic potential, supporting its potential role as a natural antianxiety agent.

Abstract in English:

Cancer cells, including those in triple-negative breast cancer (TNBC), often rely on glutamine metabolism. The enzyme glutaminase (GLS) converts glutamine to glutamate, thereby fueling the TCA cycle and affecting cell proliferation and differentiation. This metabolic dependency makes GLS a promising therapeutic target in cancer therapy, with inhibitors currently in clinical trials. Considering the key role of triazoles in medicinal chemistry and the need for the development of new drugs against cancer, we herein report the design and synthesis of a new series of 3-thio-1,2,4-triazoles from a variety of acyl hydrazines and alkyl isothiocyanates in good yields, along with 1,2,3-triazole derivatives obtained by click chemistry. A structure-activity relationship (SAR) study was performed to evaluate their potential to inhibit GLS through an enzyme inhibition assay. Among the library synthesized, compound 10k exhibited the most potent activity, exhibiting an IC50 of 9 µM. To shed light on the possible mode of interaction with GLS, molecular docking was performed, and the results point to a new allosteric binding site for compound 10k.

Abstract in English:

Hyperlipidemia, characterized by elevated cholesterol or triglyceride levels, is a key risk factor for cardiovascular diseases. This study explores the antihyperlipidemic potential of Dracaena trifasciata (Prain) Mabb., a perennial herb with diverse pharmacological properties. The ethanolic extract of D. trifasciata leaves (EEDT) was prepared and analyzed for phytochemicals. Wistar rats fed a high-fat diet (HFD) were treated with EEDT (200 mg/kg and 400 mg/kg), with statin as a positive control. Parameters assessed included lipid profiles, atherogenic indices (AIP, CRR, CPI, AC), lipid peroxidation, antioxidant levels, liver enzymes, and histopathology. Phytochemical analysis revealed flavonoids, phenols, alkaloids, and saponins, with high phenolic (776.33 mg GAE/g) and flavonoid (284 mg RT/g) content. EEDT significantly (p < 0.001) reduced total cholesterol, triglycerides, LDL, and VLDL while increasing HDL and CPI. Atherogenic indices (AIP, CRR, AC) were also significantly lowered (p < 0.001). Antioxidant markers improved (p < 0.05), and liver enzyme levels (AST, ALT, ALP) decreased (p < 0.01). Histopathological findings supported these results. EEDT demonstrated potent antihyperlipidemic and antioxidative effects, suggesting its potential as a natural therapeutic agent for hyperlipidemia and oxidative stress. However, further clinical studies are needed to confirm its efficacy and safety for therapeutic use.

Abstract in English:

Microbial biofilms are ubiquitous and highly successful forms of life. Among them, species found in food industries often include human pathogens like Salmonella spp., a significant concern due to its ability to adapt and survive in diverse environmental stresses. This bacterium is a major global public health issue, causing foodborne illnesses with considerable morbidity and economic costs. Combatting bacteria within biofilms necessitates novel strategies, and recent research highlights natural compounds as promising agents due to their antibiofilm, antivirulence, and antimicrobial properties. Specifically, plant-derived compounds have shown potential to modulate biofilm formation either alone or in combination with other substances. This review provides a comprehensive overview of Salmonella biofilms, encompassing their development, composition, resistance mechanisms, and tolerance mechanisms. It focuses particularly on the inhibition of these biofilms by plant-derived compounds.

Abstract in English:

This study evaluated the neuroprotective effects of fluoxetine in the retina of 45 Wistar rats exposed to intense light (3000 LUX for 12 hours). The animals were assigned to prevention (CG, PhotoG, and FG) and regeneration (RCG, RPhotoG, FG 7, FG 14, FG 21, and FG 30) groups, receiving daily fluoxetine treatment (10 mg/kg/day, intraperitoneally [i.p.]) either before or after photoexposure. Retinal analysis was performed using histology and histomorphometry (hematoxylin and eosin staining), detection of apoptosis (TUNEL assay), and electroretinography (ERG). Rats in the PhotoG group demonstrated reduced outer nuclear layer (ONL) thickness (~25 µm), an increased apoptotic index, and decreased b-wave amplitudes in the ERG (~60 µV), compared to controls. The FG group maintained ONL thickness (~36 µm), exhibited reduced apoptosis, and demonstrated improved electrophysiological responses. In the FG 30 group, ONL thickness increased to approximately 39 µm, apoptosis decreased, and the b-wave amplitude increased to ~120 µV, accompanied by reduced implicit times. These findings indicate that fluoxetine protects the retina against light-induced damage through antioxidant, anti-inflammatory, and antiapoptotic mechanisms, with enhanced efficacy following prolonged administration, suggesting its potential as a therapeutic agent for retinal degenerative diseases.

Abstract in English:

Organ failure remains one of the leading causes of death worldwide, posing a formidable challenge for healthcare systems. Conventional organ transplants are limited by the scarcity of donors and the risks associated with immune rejection. In response, 3D bioprinting has emerged as a revolutionary approach with the potential to fabricate tailor-made, patient-specific organs. Central to this technology is the use of bioinks-smart materials that ensure structural integrity, biocompatibility, and the functional performance of printed organs. This review delves into the latest advancements in 3D bioprinting, specifically targeting the heart and cardiac tissues, such as heart valves and entire hearts. It evaluates the capabilities of various bioprinting techniques in creating intricate tissue structures using patient-specific cells, while also addressing the potential for bioprinting to transform the landscape of organ transplantation. Furthermore, the review explores the essential properties of bioinks, the selection of cell sources, and the current progress in clinical trials and patents, offering insights into the future prospects and challenges of cardiac tissue bioprinting. This comprehensive assessment underscores the promise of bioprinting in overcoming the limitations of traditional transplants and advancing personalized medicine.