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Background: Chenopodium quinoa is a nutrient-dense pseudocereal packed with proteins, vital amino acids, and bioactive substances that may have medicinal uses. These include antioxidant, anti-inflammatory, anti-cancer, and antibacterial properties. Notably, quinoa proteins and peptides show multifunctional bioactivities such as immunological regulation, cancer cell death, and microbial suppression. This study aimed to separate, purify, and describe the bioactive proteins found in quinoa seeds, emphasizing their potential applications as medicines. Methodology: Quinoa seeds underwent protein extraction, defatting, and de-saponification. Ion exchange chromatography, dialysis, and ammonium sulfate precipitation were used to purify the seeds. The Lowry technique was used to quantify the proteins. Functional tests assessed the seeds' antibacterial, antifungal, protease, and anticancer properties, and peptide identification was carried out using LC-MS/MS. Results: The protein content decreased during purification steps, indicating effective removal of impurities. Protein fractions exhibited significant antibacterial and antifungal activities. Protease activity varied among fractions, with the pH 2 fraction showing the highest activity. Crude extract and pH 2-treated fractions demonstrated significant anticancer activity against A549 and Hela cell lines. pH 2 fraction exhibits the highest protease activity of 2.451 units/ml, indicating enhanced enzymatic capability under acidic conditions. Peptides identified from the pH 2 fraction showed potential therapeutic properties. Conclusion: The antibacterial, antifungal, proteolytic, and anticancer properties of quinoa-derived peptides and proteins demonstrate their potential for use in medicine. Clinical validation and the creation of functional foods or nutraceuticals based on quinoa should be the main objectives of future research.

Background: This study aimed to develop and evaluate an antibacterial cream emulsion containing mupirocin using Cocamidopropyl betaine (CAPB) as an emulsifier. Mupirocin, a topical antibiotic effective against Staphylococcus aureus (including methicillin-resistant strains), was formulated into a cream to enhance its topical delivery. Materials and Methods: Mupirocin cream emulsion formulations were developed with varying concentrations of CAPB, PEG-400, and glycerol monostearate. The cream formulations were mainly evaluated for in vitro diffusion tests, antibacterial activity tests, and stability studies. Result and Discussion: CAPB produced a stable cream emulsion formulation (F7) at 30% concentration and 2% PEG-400. The formulation (F7) exhibited sustained drug release over 3.5 hours in the diffusion test. The formulation F7 showed a higher zone of inhibition, 32.16±2.2 mm, than the marketed mupirocin cream, 29.56±1.35 mm, for the Staphylococcus aureus strain. The prepared cream formulation F7 was found stable over 90 days at different temperature conditions (8±2°C, 25±2°C and 40±2°C). Conclusion: The study concludes that CAPB effectively enhances mupirocin cream solubility and antibacterial properties, making it a promising option for treating bacterial skin infections.

Background: Nymphaea nouchali is a widely distributed aquatic plant prevalent in tropical and subtropical areas, flourishing in freshwater habitats. It is widely recognized as the water lily. Historically, it has been utilized in several medical systems to address conditions such as diabetes, liver diseases, and urinary tract issues. The plant comprises several bioactive substances, including flavonoids, phenolic acids, and alkaloids, which enhance its therapeutic qualities. This review examines the botanical, phytochemical, and pharmacological characteristics of Nymphaea nouchali to evaluate its medicinal potential. Methodology: This review combines data from previous botanical, phytochemical, and pharmacological research on Nymphaea nouchali. The bioactive components extracted from the plant were examined for their therapeutic capabilities. The pharmacological effects, encompassing antibacterial, antioxidant, anti-inflammatory, antinociceptive, and anticancer properties, were assessed by several in vitro and in vivo experimental methods. Results: A phytochemical study identified the presence of substances, including nymphal, gallic acid, and quercetin. These chemicals are associated with notable biological functions. Alkaloids and tannins had antibacterial activities, but phenolic compounds and flavonoids showed potent antioxidant capabilities. The herb demonstrated antinociceptive properties. Initial investigations suggested possible anticancer effects on some cell lines; nevertheless, further study is required. Conclusion: Nymphaea nouchali shows significant pharmacological potential due to its many bioactive components. Although traditional medicinal usage supports its therapeutic benefits, further preclinical and clinical investigations are necessary to validate its efficacy and safety for pharmaceutical uses.

Background: The present study aims to explore the bioactive properties of essential Oil (PKEO) derived from Picrorhiza kurroa (commonly known as kutki), a medicinal plant known for its therapeutic potential. Picrorhiza kurroa essential oil has a distinct chemical profile, which sets it apart from other essential oils. The bioactive compounds present in Picrorhiza kurroa essential oil may lead to the development of new drugs, particularly for treating inflammatory and oxidative stress-related disorders. The research aims to study the extraction, phytochemical composition, and various biological activities of PKEO. Methodology: Oil obtained through hydro-distillation contains various phytochemical compounds, including steroids, triterpenoids, alkaloids, phenols, proteins, flavonoids, and tannins. Its bioactivity and aroma are attributed to its phenolic and sesquiterpene esters. Results and Discussion: The total phenolic content is 250.47 μg GAE/g, and the total flavonoid content is 245.26 μg QE/g. UV-visible and IR spectroscopic analyses confirm the presence of phenolic and terpenoid ester functional groups. PKEO has moderate antioxidant activity, with IC50 values of 98.19 µg/mL in DPPH scavenging and 42.72% inhibition in the ABTS assay. It also exhibits dose-dependent inhibition of protein denaturation and HRBC stabilizing activity. Antimicrobial tests show PKEO inhibits E. coli growth, indicating potential antibacterial properties. Conclusion: These findings highlight PKEO's promising bioactive profile, suggesting potential therapeutic and cosmetic formulation applications. The antifungal activity also shows the potential antifungal effects of the PKEO.

Background: With growing awareness of pomegranate's health benefits, pomegranate products have been consumed more frequently in recent years, and pomegranate peel has emerged as one of the most prevalent wastes in the food industry. Pomegranate Peel concentrate is an indigenous substance with strong antioxidant and antidiabetic actions as a result of its tannins as well as polyphenols content. Methods: In the present study, pomegranate skin extract, both liquid and alcohol-based, was evaluated for polyphenolic and flavonoid content. Alcoholic fruit peel extract was also assessed for 1,4-α-D-glucan glucanohydrolase and α-D-glucoside glucohydrolase enzyme activity. Results: According to findings, pomegranate peel extract showed significant antioxidant content. Phytochemical analysis of ethanol-derived extract of pomegranate peel found a noteworthy amount of ellagitannins and flavonoids such as Punicalin, Punicalgin, Punicic acid, Catechin, Quercetin, Rutin, and Kaempferol. In contrast, punicalgin, ellagic acid, and gallic acid are responsible for antidiabetic activity. The LC-MS characterization of peel extract of pomegranate showed 10 bioactive compounds. The IC50 value for 80% alcoholic extract of pomegranate peel was found to be 5.86 mg/ml of α- amylase and 6.58 mg/ml of α-glucosidase. Conclusion: It was found that the inhibition of 1,4-α-D-glucan glucanohydrolase and α-D-glucoside glucohydrolase enzymes could be an effective mechanism by which it can give anti-diabetic effects.

Background: Moringa oleifera Lam., widely known as ‘The Tree of Life’, is a medicinal tree native to India and extensively grown in tropical regions worldwide. In India, Tamil Nadu is the leading state, engaging an area of 20684 hectares in the production of moringa. In South India, moringa is extensively utilized as a vegetable for its exquisite taste and flavor in sambar and curry preparation. Methodology: Phytochemical analysis of leaves from the Tamil Nadu region and simultaneous estimation of quercetin, rutin, and gallic acid contents in moringa leaf extracts from the Tamil Nadu region via HPTLC analysis was carried out. DPPH assay was performed to determine the antioxidant potential. Results and Discussion: The hydroalcoholic extract obtained from the triple maceration of moringa leaves possesses high amounts of phytoconstituents such as flavonoids and polyphenols. Each gram of the extract contained 1650.401 µg of quercetin, 1136.950 µg of rutin, and 220.223 µg of gallic acid. The IC50 value of the extract was calculated to be 36.10 µg/ml. Conclusion: The extract from the leaves of the moringa plant grown in the Tamil Nadu region contains a good amount of phytoconstituents and also possesses good antioxidant activity comparable to that of standard ascorbic acid, suggesting its potential use as an antioxidant agent. The findings of the present study support the traditional use of the folklore plant for improving health.

Background: Aloscasia macrorrhiza, commonly known as Giant Taro, is a species rich in phytochemicals with diverse pharmacological properties. Phytochemical analysis shows different bioactive compounds like alkaloids, flavonoids, terpenoids, phenolics, and saponins in different components of the plant body, including leaves, stems, and roots. Alocasin, a class of alkaloids, is most prominent in this plant. These substances are likely responsible for different biological activities, as Aloscasia macrorrhiza shows. Aim: This review unveils the phytochemical composition and pharmacological activities of various parts of Aloscasia macrorrhiza. Method: Multiple Literature, including research and review papers, were searched for based on their title, abstracts, and keywords. Keywords like ‘Aloscasia macrorrhiza,’ ‘Phytochemistry,’ ‘Traditional uses,’ and ‘Ethnomedicinal uses’ were used to collect information. Abstracts of articles with relevant titles were screened, and the full text was considered. Only articles published from 2018 to 2024 were considered. Based on their classes and mechanistic actions, this review consolidated these phytoconstituents. Results: These phytoconstituents exhibit a wide array of therapeutic activities, including anti-inflammatory (due to tannins and polyphenols), antimicrobial (due to terpenes and lectins), antioxidant (due to polyphenols), anticancer (due to flavonoids), anti-diabetic (due to flavonoids) effects. Conclusion: This review provides insights to the therapeutic potential of Aloscasia macrorrhiza and hence forms a bridge of understanding between the traditional uses and the modern Pharmacology studies. In the future, further clarification and detailed mechanistic insight can be done. Aloscasia macrorrhiza may have potential therapeutic applications and is subject to further investigation.

Background: Research on diabetes treatment is advancing yearly, and it is estimated that 643 million adults worldwide will have diabetes by 2030. This is a comprehensive review of antidiabetic mechanisms in medicinal plants, aims to identify natural antidiabetic plants and provide details on their mechanisms of action, and rigorous testing techniques. Methodology: Information was gathered from offline and online sources to identify indigenous medicinal plants that lower blood glucose. Different databases were searched for ethnopharmacological literature using the following keywords: medicinal plants, diabetes, and India. Other sections about clinical trials, toxicological evaluations of certain plants, and preclinical trials have since been added. These sections were retrieved from Scopus using pertinent keywords. In this study, 117 species of medicinal plants from 55 families that are used to treat diabetes mellitus were listed. Conclusion: The variety of plants discussed in this review clearly demonstrated the importance of herbal plants in the treatment of diabetes. Result of the study shows Fabaceae, Rutaceae, and Combretaceae were the most prevalent plant families and species having antidiabetic properties among these plants. It also gives researchers information that they may use to develop future plans, like finding plants that may be effective in preventing diabetes and isolating bioactive molecules to help manage the disease. More research is necessary to completely comprehend these newly identified anti-diabetic drugs at the molecular, therapeutic, and physiological levels, nevertheless, in order to treat and manage diabetes mellitus globally

Background: In Parkinson's disease (PD), a complicated neurodegenerative ailment, neurons in the substantia nigra that produce dopamine are lost, resulting in an insufficiency of the neurotransmitter that is essential for the regulation of voluntary and smooth muscular movements. This review focuses on the obstacle triggering the effectiveness of traditional PD treatments, which is the blood-brain barrier (BBB), which prevents some therapeutic medicines from reaching the brain. It encompasses the potential strategy of nose-to-brain administration by innovative approaches, including nanoparticles, liposomes, dendrimers, and cell-based carriers, directly delivering the drugs from nose to brain. Methods: The methodology involved examining the characteristics, advantages, applications, and challenges of various nanoparticles like SLNs, Nanoliposomes, Quantum dots, dendrimers, etc., through meticulous analysis of articles including from PubMed (5), ScienceDirect (5), Bentham Science (4) and Scopus databases (5). Conclusion: The review concludes by emphasizing the potential applications of nanoparticles in circumventing the problems encountered with traditional methods of drug administration in treating PD. This detailed study brings to light the applications and the challenges that need to be faced in utilizing nanoparticles for nose-to-brain delivery. Attention is directed towards the enlightenment of advanced carriers that target specific brain regions via the olfactory and trigeminal routes. The drug directly reaches the brain, bypassing BBB.

Background: This study investigated the effects of Cuminum cyminum (C. cyminum) on cognitive behaviour and acetylcholinesterase (AChE) levels in diabetic rats, comparing its efficacy with Glibenclamide, Sulbutiamine, and Resveratrol. Methods: Wistar rats were randomized into 12 groups (n=10) half diabetic and half non-diabetic controls and administered C. cyminum 500 mg/kg and 1000 mg/kg, Glibenclamide (5 mg/kg), Sulbutiamine (50 mg/kg), and Resveratrol (25 mg/kg). Controls included diabetic and non-diabetic rats without treatment. Blood glucose, insulin, oxidative stress markers, and AChE levels were measured, along with behavioural parameters of learning and memory using the elevated plus maze, passive avoidance, and Morris water maze. Results: Both doses of C. cyminum significantly reduced blood glucose levels (Dose I decreased blood glucose levels from 278.5 ± 3.66 mg/dl to 136.8 ± 4.91 mg/dl while dose II decreased the blood glucose levels to 138.8 ± 3.83 mg/dl) and improved learning and memory, as evidenced by faster transfer latency (TL) and better retention in the elevated plus maze and Morris water maze. The higher dose was particularly effective in reducing brain AChE levels and improving cognitive performance in passive avoidance tests. Conclusion: Both doses of C. cyminum decreased the AChE activity induced by diabetes, improving learning and memory. The antioxidant and anti-hyperglycaemic potential may partially contribute to delaying cognitive impairment. Thus, the study suggests that C. cyminum may be beneficial in mitigating behavioural and biochemical changes associated with diabetes mellitus, offering potential as a complementary therapy to existing diabetes treatments. Elaborate studies in the future are essential to explore its antidiabetic and neuroprotective potential.

Background and purpose: Lom-Am-Ma-Pruek (LAMP) remedy has been used in Thai traditional medicine to relieve pain associated with the inflammatory process. The anti-inflammatory activity and bioactivity of LAMP in an animal model have not been previously investigated. We evaluated the in-vitro and in-vivo anti-inflammatory activity of LAMP ethanol extract. Experimental approach: The anti-inflammatory activity of LAMP and its plant ingredients were investigated on lipopolysaccharide-stimulated NO, PGE2, and TNF-α release from RAW264.7 cells. Furthermore, the stability of LAMP under biological and chemical accelerated conditions was evaluated using the Griess reaction assay and HPLC. Lastly, rat models with ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema were utilized to assess anti-inflammatory activity. Findings/Results: LAMP possessed potent inhibitory effects on NO, PGE2, and TNF-α production with IC50 values of 24.90 ± 0.86, 4.77 ± 0.03, and 35.01 ± 2.61 µg/mL, respectively. In addition, LAMP extract demonstrated stable biological activity, anti-inflammatory effects, and phytochemical content stability under stress conditions. Additionally, 0.5%, 1%, and 2% w/v LAMP significantly inhibited EPP-induced rat ear edema over time equivalent to 5% w/v phenylbutazone. LAMP at 180, 375, and 750 mg/kg also considerably reduced carrageenan-induced rat paw edema 2 h after carrageenan administration compared to phenylbutazone at 250 mg/kg. Conclusion and implications: LAMP has anti-inflammatory activity by inhibiting PGE2 formation. These findings are consistent with the efficacy and traditional use of the LAMP remedy in treating inflammatory diseases.

Background and purpose: Combined hyperlipidemia is associated with an increased risk of cardiovascular events. This clinical trial investigated phospholipovit (essential phospholipids, Institute of Biomedical Chemistry, Moscow, Russia), an ultra-small phospholipid nanoparticle (micelles), targeted to phospholipids of HDL in lowering non-HDL-cholesterol (non-HDL-C) and triglycerides (TG) levels in patients with combined hyperlipidemia and moderate cardiovascular risk. Experimental approach: A randomized, double-blinded, placebo-controlled phase II trial was conducted on 100 patients. Phospholipovit or placebo was randomly administered orally (500 mg) 2 times a day for 12 weeks. The primary endpoint was the percent change of non-HDL-C from baseline to 12 weeks of exposure. Findings/Results: Treatment with phospholipovit resulted in a mean non-HDL-C reduction of 13.2% versus 4.3% compared with placebo. The absolute decrease in non-HDL-C was -23.2 (-48.7 - 7.0) mg/dL versus -7.3 (-17.0 - 12.0) mg/dL, significantly. The therapeutic target of non-HDL-C less than 130 mg/dL (3.4 mmol) was achieved in 15 of 39 patients (38.5%) in the phospholipovit group versus 2 of 41 patients (4.9%) in the placebo group OR 11.8 (2.4 - 116). Significant reduction in TG, apolipoprotein B, total cholesterol, and very low-density lipoprotein cholesterol levels was also observed. There were no changes in the liver and kidney functions, vital signs, or electrocardiography. There were no serious adverse events. Conclusion and implications: Phospholipovit significantly reduced non-HDL-C, TG, and atherogenic lipoproteins in patients with combined hyperlipidemia and moderate cardiovascular risk. It can be used as an add-on therapy to statins.

Background and purpose: Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these Leishmania major proteins. Experimental approach: The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses. Findings/Results: The results demonstrated the vaccine’s antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes. Conclusion and implications: These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects.

Background and purpose: Pyrrosia longifolia is one of the medicinal plants in Indonesia. However, it has received little attention regarding pharmacological properties and phytochemicals. This study aimed to isolate bioactive compounds and evaluate their antibacterial activities. Experimental approach: The secondary metabolites were isolated using a bioassay-guided approach. The aerial part was macerated in methanol and the crude methanol was partitioned with organic solvents to obtain n-hexane, dichloromethane, ethyl acetate, and water extracts. The ethyl acetate extract was purified using chromatography procedures, yielding six chemicals, and their structures were determined using spectroscopy. The antibacterial activity of the compounds was evaluated. Findings/Results: Six secondary phytochemical metabolites were identified including naringin (1), catechin (2), quercetin (3), rutin (4), kaempferol (5), and mangiferin (6). The absolute configurations of compounds 1 and 2 were ascertained using electronic circular dichroism as 2S for naringin and 2R, 3S for catechin. The compounds exhibited antibacterial activity against several pathogenic bacteria, with MIC and MBC values ranging from 7.8 to 250 μg/mL. Computational investigations of these compounds revealed a substantial affinity for bacterial receptors’ active and allosteric regions. Furthermore, rutin exhibited the capacity to reduce the activity of β-ketoacyl-acyl carrier protein synthase III, enhancing its antibacterial effectiveness. Conclusion and implications: The in-vitro assessment revealed that the six identified compounds possess a wide range of antibacterial activity, which was corroborated by in-silico analyses. However, further investigation is required to back up the conclusion of this study.

Despite the recent therapeutic advances in neurological disorders, curative therapy remains a serious challenge in many cases. Even though recent years have witnessed the development of gene therapy from among the different therapeutic approaches affecting pathophysiological mechanisms, intriguing aspects exist regarding the effectiveness, safety, and mechanism of action of gene therapies. Micro ribonucleic acid (microRNA-miRNA), as a fundamental gene regulator, regulates messenger ribonucleic acid (mRNA) by directly binding through the 3′-untranslated region (3′-UTR). MicroRNA-219 is a specific brain-enriched miRNA associated with neurodevelopmental disorders that play crucial roles in the differentiation of oligodendrocyte progenitorcells, promotion of oligodendrocyte maturation, remyelination, and cognitive functions to the extent that it can be considered a potential therapeutic option for demyelination in multiple sclerosis and spinal cord injury and reverse chronic inflammation pains. Additionally, miR-219 regulates the circadian clock, influencing the duration of the circadian clock period. This regulation can impact mood stability and is associated with phase fluctuations in bipolar patients. Furthermore, miR-219 also plays a role in modulating tau toxicity, which is relevant to the pathophysiology of Alzheimer’s disease and schizophrenia. Finally, it reportedly has protective effects against seizures and Parkinson’s disease, as well as neoplasms, by inhibiting proliferation, suppressing invasion, and inducing cell death in tumor cells. Exploring the miR-219 molecular pathways and their therapeutic effects on central nervous system disorders and the mechanisms involved, the present review study aims to illustrate how this information may change the future of gene therapy.

Background and purpose: Chlorogenic acid (CA) is a natural chemical that promises antiaging activity against photoaging skin damage. This research examined CA activities in mitigating skin photoaging. Experimental approach: UV-exposed human skin fibroblast cells were subjected to CA at 6.25, 12.5, and 25 μg/mL. The protein levels of cell secretion, such as cyclooxygenase (COX)-2, nitric oxide (NO), and interleukin (IL)-6 were measured using ELISA and colorimetry methods. Meanwhile, the mRNA expressions of glutathione peroxidase (GPX)-1, tissue inhibitor metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-1, caspase (CASP)-3, CASP-8, and fibroblast growth factor (FGF)-2 were quantified using the qRT-PCR method. Findings/Results: CA treatment reduced inflammatory and aging biomarkers. CA at 6.25 μg/mL lowered NO, COX-2, and IL-6 levels to 89.44 μmol/L, 8.10 ng/mL, and 62.75 pg/mL, respectively. CA at 25 μg/mL resulted in the most significant down-regulation of MMP-1, CASP-3, and CASP-8 genes’ expression (3.27, 1.25, and 3.59, respectively). Furthermore, treatment with CA at 25 µg/mL demonstrated the most notable activity in up-regulating antioxidant markers, specifically GPX-1, and extracellular matrix (ECM) integrity markers, including TIMP-1 and FGF-2 genes’ expression. Conclusion: CA imposes its anti-aging activity by decreasing inflammatory and aging biomarkers, and increasing cellular antioxidant and ECM integrity.

Intracellular delivery is crucial in biological and medical studies. Although many molecular tools have been created for cell-based gene therapies, it remains challenging to introduce external molecules into cells. As one of the most popular non-viral transfection methods, electroporation induces transient pores in the cell membrane by applying an external electric field. Unsatisfactory transfection efficiency and low cell viability are the major drawbacks of electroporation. To overcome these issues, the current study investigated the effect of urea on electroporation-mediated transfection efficiency. Experimental approach: Three voltages of electroporation, including 100, 120, and 140 V, and 3 concentrations of urea buffer, including 0.25%, 0.5%, and 1% W/V, were considered as variables in this study. The HEK-293 cell line was used for transfection, and green fluorescent protein (GFP) expression was evaluated using flow cytometry and fluorescence microscopy. Findings/Results: The results showed that the combination of electroporation and urea increased electroporation efficacy, but the effect depended on voltage and urea concentration. When different concentrations of urea were added to HEK-293 cells at a voltage of 100 V, the number of cells transfected by pEGFP-N1 increased (from 12.3 ± 0.2% in untreated cells to 17.35 ± 0.55%, 23.3 ± 0.3%, and 14 ± 0.1% at urea concentrations of 0.25%, 0.5%, and 1% W/V, respectively). The electroporation buffer containing 0.5% W/V urea showed the highest EGFP expression (23.3 ± 0.3%) and high cell viability (over 90%). Conclusion and implications: This research offers a new perspective for improving gene transfection efficiency once electroporation is utilized.

Background and purpose: Lapatinib (FMM) and 5-fluorouracil (5-FU) are anticancer drugs employed in a combination approach. FMM inhibits tyrosine phosphorylation of ErbB4 while 5-FU inhibits cell proliferation. This research aimed to investigate the potential of two compounds, namely (1E,4E)-1,5-bis (4-hydroxyphenyl) penta-1,4-dien-3-one (AC01) and (1E,4E)-1,5-bis (3,4-dihydroxy phenyl) penta-1,4-dien-3-one (AC02), both as individual inhibitors and combination partners with FMM, targeting ErbB4 inhibition. AC01 and AC02 were combined with FMM, which targets ErbB4. The combination of 5-FU with FMM served as a reference in this study. Experimental approach: The research utilized computational simulation methods such as single and multiple ligands simultaneously docking and dynamics. Data analysis was performed using AutoDockTools and gmx_MMPBSA. Findings/Results: Single docking results indicated that 5-FU exhibited the lowest binding affinity, while FMM demonstrated the highest. Simultaneous docking of AC01 and AC02 paired with FMM revealed their binding positions overlapping with the FMM-5-FU workspace. The FMM-AC01 and FMM-AC02 complexes exhibited slightly weaker binding affinities compared to FMM-5-FU. In combination with FMM, AC01 and AC02 occupied the ErbB4 activation loop, whereas 5-FU was outside the activation loop. Furthermore, in their interaction with ErbB4, AC02 exhibited slightly stronger binding than AC01, as confirmed by the average binding free energy calculations from molecular dynamics simulations. Conclusion and implications: In conclusion, computational simulations indicated that both AC01 and AC02 have the potential to act as anticancer candidates, demonstrating ErbB4 inhibitory potential both as individual agents and in synergy with FMM.

Background and purpose: Xanthohumol (Xn), a small molecule found in Humulus lupulus, has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation. Experimental approach: After ligand and protein preparation, the best binding energy was determined using Autodock 4.2. Additionally, molecular dynamics simulations of the MEK1/2-Xn and BRaf-MEK1/2-Xn complexes were conducted using GROMACS 2022.1 software and compared to the complexes of MEK1/2-trametinib (Tra) and BRaf-MEK1/2-Tra. Findings/Results: The docking results revealed that the best binding energies for MEK1-Xn (-10.70 Kcal/mol), MEK2-Xn (-9.41 Kcal/mol), BRaf-MEK1-Xn (-10.91 Kcal/mol), and BRaf-MEK2-Xn (-8.54 Kcal/mol) were very close to those of the Tra complexes with their targets, MEK1 and MEK2. Furthermore, Xn was found to interact with serine 222 at the active site of these two kinases. The results of the molecular dynamics simulations also indicated that Xn induced changes in the secondary structure of the studied proteins. The root mean square of proteins and the mean radius of gyration showed significant fluctuations. Conclusion and implications: The findings of the study suggested that Xn, as a novel bioactive compound, potentially inhibits the MEK1/2 function in cancer cells.

Background and purpose: Alzheimer’s disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer’s Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates. Experimental approach: A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman᾽s test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil. Findings/Results: Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC50 = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC50 = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil. Conclusion and implication: The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase.

Dyslipidemia is a major risk factor for coronary heart disease and is responsible for an estimated 2.6 million deaths annually. Hypertensive patients often suffer from dyslipidemia, which can lead to complications such as ischemic heart disease and stroke. This study examined the prevalence and factors associated with dyslipidemia among adult hypertensive patients admitted to Lira Regional Referral Hospital (LRRH) in Uganda. This cross-sectional study, conducted over three months at Lira Regional Referral Hospital (LRRH), involved 431 patients. Medical examinations and histories were recorded, and blood samples were analyzed to measure high-density lipoprotein (HDL), low-density lipoprotein (LDL-c), total cholesterol (TC), and triglycerides (TG). Dyslipidemia was defined by any of the following: TC ≥200 mg/dL, TG ≥150 mg/dL, HDL-C < 40 mg/dL, or LDL-C ≥100 mg/dL. The data were analyzed using binary logistic regression in SPSS version 26 to identify associated factors. A total of 431 patients were included in the study, with the majority being females over 65 years of age (mean age = 64.7, SD = 8.8 years). The prevalence of dyslipidemia was 48.3% (208) (95% CI = 43.2-52.9%). High LDL levels were observed in 24.4% (105), high TC in 22.5% (97), high TG in 20.0% (86), and low HDL in 20.0% (86 patients). Multivariate analysis revealed that patients with elevated blood pressure, stage 1 hypertension, and stage 2 hypertension had 1.350 (aOR = 1.350, CI = 1.194-1.525, P < 0.001), 1.290 (aOR = 1.290, CI = 1.123-1.482, P < 0.001), and 1.302 (aOR = 1.302, CI = 1.077-1.576, P = 0.007) times higher odds of having dyslipidemia, respectively. Additionally, dyslipidemia was 1.414 times more common (aOR = 1.414, CI = 1.280-1.561, P < 0.001) among current or former smokers and 1.493 times more common (aOR = 1.493, CI = 1.372-1.625, P < 0.001) in patients with diabetes mellitus. The findings highlight a high prevalence of dyslipidemia, emphasizing the need for targeted interventions. Enhancing patient education on antihypertensive therapy adherence and increasing efforts to discourage smoking are crucial steps to reduce the burden of dyslipidemia in hypertensive populations.

Staphylococcus aureus (S. aureus) is a major human pathogen that is able to develop resistance to multiple antibiotics with significant challenges in clinical treatment. The aims of this paper were to summarize the current understanding of S. aureus resistance to various antibiotic classes in Iraq, highlighting mechanisms of resistance, prevalence rates, and the need for further research. We conducted a narrative review using thematic approach to investigate the antibiotic sensitivity of S. aureus through searching two websites PubMed and Google Scholar S. aureus resists β-lactam antibiotics through low-affinity PBP2a or β-lactamases. High resistance rates were observed in Iraq, with BlaZ gene sequences showing 100% similarity to those in other countries, suggesting a common origin or spread of genetic variants. Reports from Iraq revealed a high MRSA carriage rate among healthcare workers and the general community. Vancomycin resistance, mediated by vanA and vanB genes, has been reported globally. In Iraq, an 8% prevalence of VRSA was observed. Regarding MLS-B, tetracycline, and quinolone resistance, limited data from Iraq about the sensitivity pattern of these antibiotics is available. The available data are limited, highlighting significant gaps in understanding the full scope of resistance patterns. The high prevalence of antibiotic resistance in S. aureus in Iraq underscores the urgent need for comprehensive studies with international collaboration to develop effective public health strategies and improve antibiotic stewardship programs in Iraq.

Sickle haemoglobin (HbS) is the most common abnormal haemoglobin mutation worldwide. In Uganda, according to the Uganda Sickle Surveillance Study (US3), the overall prevalence of sickle cell trait and disease is 13.3% and 0.7%, respectively. SCD presents with numerous complications. Acute Soft Head Syndrome (ASHS) or sickle cell cephalohematoma is among the rare complications of SCD. We report a 14-year-old adolescent male, a resident of rural Western Uganda, who presented with a history of non-traumatic painless scalp swelling for a week and multiple joints pain for 5 days. He had a similar swelling in the previous six months, which subsided after blood transfusion given at a nearby health facility. There was a history of on-and-off fever, easy fatiguability, and generalized body weakness. Complete blood counts revealed anemia, Haemoglobin Electrophoresis confirmed Sickle Cell Anemia. Head Computed Tomography concluded a subgaleal fluid collection. The diagnosis of acute soft head syndrome was established in a newly diagnosed SCD patient. This case highlights a rare diagnosis of acute soft head syndrome as well as a late diagnosis of SCD in adolescent in rural settings. In such settings, the pre-existing poor socio-economic background coupled with atypical presentation constitute a major impediment for timely diagnosis.

Mental health is a crucial aspect of well-being, especially among undergraduate nursing students. Nursing students face unique stressors that can impact their mental health. This study aimed to determine the anxiety and depression levels among undergraduate nursing students at Chattogram, Bangladesh. A cross-sectional study design was employed, and data were collected using an online questionnaire (Google form) that included the Hospital Anxiety and Depression Scale (HADS). Convenience sampling was used to select 124 BSc Nursing students aged over 18 years. Data analysis was conducted using SPSS version 28. The majority of participants were female (88.3%), and the mean age was 20.58 years, range 18 to 23. The prevalence of anxiety was 66.0%, with 28.0% scoring in the borderline abnormal range and 38.0% in the abnormal range. For depression, 22.4% were in the borderline abnormal range, and 18.4% were in the abnormal range. Pearson correlation test showed gender was significantly associated with anxiety (p = 0.004). At the same time, no significant associations were found between depression and gender, depression and academic qualifications, contagious disease status, or close family members' infection status. The logistic regression analysis reveals that age is significantly associated with depression among nursing students; older students have higher odds of experiencing depression (OR = 1.384, p = 0.037). This study highlights a significant burden of anxiety among undergraduate nursing students at CINC, with a substantial proportion experiencing abnormal levels of anxiety. The findings underscore the importance of addressing mental health issues among nursing students and implementing strategies to promote their mental well-being.

Birth spacing is the interval between a live birth and a subsequent pregnancy, which is recommended to be at least two years. This study aimed to identify the determinants of birth spacing practices among parous mothers attending antenatal clinics in Port Harcourt, Nigeria. A cross-sectional study was conducted among 410 parous mothers aged 15–49 in Port Harcourt, Nigeria, from June to October 2024. A multistage sampling procedure was used to select the respondents, and data were collected using a semi-structured, interviewer-assisted questionnaire. Frequency tables were generated, and a binary logistic regression model was used to identify the determinants of birth spacing practices at a 5% significance level. The respondents’ mean age was 35.2 ± 3.9 years. The prevalence of birth spacing practice was 36.6%, with condoms (13.7%) being the most commonly used contraceptive method. Determinants such as attaining secondary education (OR = 1.9; 95% CI = 3.6–11.8; P = 0.00), tertiary education (OR = 1.5; 95% CI = 2.6–7.6; P = 0.00), employment status (OR = 2.4; 95% CI = 1.4–4.1 ; P = 0.00), knowledge of birth spacing (two-year interval (OR = 3.5; 95% CI = 1.6–7.4; P = 0.00), knowledge of the benefits of birth spacing (OR = 2.6; 95% CI = 3.7–46.4 P = 0.00), and spouse consent (OR = 3.8; 95% CI = 2.5–5.8; P = 0.00) significantly contributed to the practice of birth spacing among parous mothers.

Controlling cholesterol levels and reducing the risk of cardiovascular disease requires the development of effective therapeutic strategies. In recent decades, dietary supplements (DSs) have gained attention as potential additions to conventional cholesterol management therapies, but their efficacy and safety are questionable. Accurate methods are required to evaluate the efficacy and safety of DSs. In the current study gas chromatography mass spectrometry was performed to analyze ten cholesterol-reducing DSs. The results showed that monacolin K/lovastatin was present in four samples. Moreover, using effective doses generally has minimal risks and lower incidence of adverse reactions and drug interactions. However, it must be taken into account the potential interaction of statins to induce myopathy and rhabdomyolizis. In order to prevent adverse effects, it is necessary to thoroughly evaluate and be careful when using DSs containing monacolin K.

The potency of the cannabinoids depends on the accuracy of the values of water content in the medicinal Cannabis flowers. Since the water in the plant material greatly affects its contamination susceptibility and product consistency, an accurate analysis of water content in medicinal Cannabis flowers is necessary to ensure product quality and safety, as well as compliance with numerous state and local regulations. The aim of this research was to develop a specific, accurate, fast, and reliable method for selective determination of water at wide concentration ranges in different varieties of Cannabis flowers for medicinal use. The intended use of the method was the evaluation of the quality of the starting material for production of Cannabis extract. Considering that the Karl Fischer titration (Ph.Eur. 2.5.12) is the only established specific test for quantification of water in a wide variety of samples at wide concentration ranges, its suitability for medicinal Cannabis flowers was demonstrated by proposing suitable titrant-solvent combination, followed by verification of the accuracy, linearity, and sensitivity of the method. The obtained results for water content in more than 40 samples of different Cannabis varieties were in range from 3.8 to 8.5%. The values indicate only water content and do not include amounts of other volatile compounds, such as terpenes, as well as cannabinoids, which can be incorrectly classified as moisture content when using thermogravimetric methods. The proposed method has suitable selectivity, accuracy, and sensitivity for the intended purpose. The small sample amount, in addition to the simple operation conditions and fast analysis allows the use of the method for ‘in process’ control for Cannabis flowers.

The purpose of this research was to use the vertical diffusion cell method to produce an appropriate in vitro release test for topical gel formulations. In order to occur a topical drug product's pharmacological activity, the active pharmaceutical ingredient (API) must first be released from the vehicle and be available to penetrate the skin layers and reach the site of action. Formulation properties (characteristics / factors) have the greatest influence on drug release. Concepts presented in the EMA's draft guideline on topical product quality and equivalence were utilized to analyze critical qualification factors and validate in vitro release test (IVRT) methods. Factors that may influence the test, such as the receptor medium and membrane qualification, were appropriately evaluated, followed by an evaluation of method accuracy and method robustness. With 50% and 400% (200% for 2.32% gel) API formulations, the linearity of the IVRT technique as a function of drug concentration in the formulation was studied. Furthermore, the method's discriminatory power was proven using a formulation with variable viscosity as a significant quality parameter. A permeation study of API at 24 h and drug release rate was performed based on Strat-M membrane permeability parameters in order to predict the outcome of the in vitro permeation testing (IVPT). API release profile comparison fulfilled the applicable acceptance criteria for the 90% confidence interval (CI) for the ratio of means of the pairwise comparisons

Lepidium meyenii Walp. (Brassicaceae) is a plant native to the Andean region. It is also known as Maca and Peruvian ginseng and is considered to have been used in traditional medicine for more than 2000 years. Lepidium meyenii is regarded as a plant adaptogen. Nowadays, Maca root is used worldwide as a food, tonic, antioxidant, enhancer of fertility, etc. The main compounds in the underground part of the plant are glucosinolates, thiohydantoins, isothiocyanates, macamides, macaene, fatty acids, polysaccharides, alkaloids, fiber, lipids and proteins, which are responsible for various biological activities including antimicrobial, antioxidant, cytotoxic, anti-inflammatory and immunomodulatory activities. The purpose of this review is to summarize the data of some in vitro, in vivo and clinical studies on the biological activity of Maca and to analyze the future perspectives for the inclusion of Maca into novel herbal medicines

Implementation of analytical quality by design approach is a helpful tool in development of a robust analytical method which is applicable throughout the lifecycle of the product. This model is perfect strategy for analytical method development, in order to reduce outof-trend (OOT) and out-of-specification (OOS) results and to achieve high degree of robustness, providing cost-effective analytical method. The aim of this study was to implement a software which uses experimental design plans as an efficient and fast tool for development of method for quantitative determination of content of ACE inhibitor in tablets. Using statistical models in method development and optimization, the effect of each factor on responses of interest were calculated and the data were used to find the optimal chromatographic conditions. Best chromatographic separation within run time of 13 minutes was achieved on column Zorbax SB C18, 150 x 4.6 mm, (5 µm), using a mixture of 15 mM phosphate buffer pH 1.8 and acetonitrile as a mobile phase, with gradient elution and column temperature maintained at 60 °С. The validated method is specific, linear, accurate, precise and robust for the determination of angiotensin - converting enzyme inhibitor in tablets.

International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines provide guidance for stability monitoring of medicines which Food and Drug Administration (FDA) and European Medicines Agency (EMA) refer to. A full stability study design is described as a model in which samples under the influence of appropriate factors are tested at all-time points. Bracketing and matrixing stability study designs represent reduced designs that may be a suitable alternative to a full stability design. Bracketing design refers to the stability such that only samples on the extremes of certain design are tested at all-time points as in a full design, whereas the stability of the intermediate levels is represented by the stability of the tested extremes, which reduces costs and time analysis. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. Bracketing design of four different dosage strengths of Fluconazole hard capsules is included in this research. The extreme strengths were chosen and parameters average mass of capsule contents, disintegration, dissolution, assay of active and related substances, according to shelf-life specification were tested in accelerated and long-term stability conditions. Based on the obtained results, the stability of any intermediate levels is confirmed by the stability of the tested extremes and show that this reduced design is suitable.

Analytical laboratories should confirm the traceability of volumetric measurements used in support of testing and calibration activities, by establishing procedures for calibration and check of the laboratory glassware used in volumetric measurements. Different national accreditation bodies establish different minimum requirements for the volumetric glassware used in a laboratory, regarding the validity of the calibration and the frequency for the verification of the suitability of the volumetric glassware. The intervals, methods, and specification criteria for qualification of volumetric glassware usually are established by each laboratory, taking into account the type of equipment following the relevant standard requirements. We have estimated the measurement uncertainty of the volumetric equipment that is mostly used in the laboratory for quality control of medicines (volumetric flasks, single-volume pipettes, and burettes), and identified that the temperature effect and meniscus reading (precision and accuracy) are the most contributing sources in the uncertainty. Additionally, we have performed statistical evaluation by comparing the obtained results with the calibration certificate values and with the experimental results from qualification in previous years. Based on the obtained results it was concluded that the defined frequency of calibration once a year can be extended, as long as the measurements are performed according to the standard operating procedures and in strictly controlled environmental conditions.

The efficient and accurate investigation of Out of Specification (OOS) results is crucial in maintaining the reliability and quality of products in a physico-chemical laboratory. This paper presents a comprehensive workflow designed to systematically and effectively manage OOS results in such laboratories. The workflow integrates established quality assurance principles, regulatory guidelines, and best practices to ensure robust and reliable investigations. The presented workflow comprises several key stages, each designed to address specific aspects of the investigation process. The workflow provides a structured and systematic approach to investigating OOS results in physico-chemical laboratories. By incorporating data-driven decision-making, root cause analysis, and corrective actions implementation, laboratories can uphold product quality, regulatory compliance, and customer satisfaction. This workflow serves as a valuable tool for laboratories seeking to enhance their OOS investigation processes and overall quality management systems.

Antioxidant status in patients with chronic myeloid leukemia (CML) is significantly decreased in comparison with healthy individuals. Oxidative stress (OS) may be associated with the pathophysiology of CML and can influence on development of resistance to imatinib. The aim of our study was to investigate the effect of Aronia melanocarpa extract (A-lixir 400 PROTECT®) on OS in CML patients treated with imatinib. In this study a total of 40 CML patients treated with imatinib for longer than 1 month were included: twenty patients were treated with imatinib and A-Lixir 400 PROTECT® (treatment group) and twenty patients were treated only with imatinib (control group). OS parameters (d-ROM, PAT and OSI) were measured at the initial visit, and after 21 and 42 days of treatment. Adjuvant treatment with A-Lixir 400 PROTECT® could lead to attenuation of OS. d-ROM and OSI in this group of patients were significantly higher at initial visit when compared to values after 21 and 42 days of treatment (p

One of the new ways of drug delivery that is being developed more and more often recently is orodispersible tablets (ODTs), also known as orally disintegrating tablets, rapidly dissolving tablets and fast-dissolving tablets. The European Pharmacopoeia (Ph. Eur.) defines ODTs as uncoated tablets intended to be placed in the mouth where they disperse rapidly before swallowing, disintegrating within 3 minutes. ODTs come with many advantages such as: easy swallowability especially for paediatric, geriatric and bedridden patients, аs well as for people with lack of access to water; fast release of API and fast onset of action; and enhanced bioavailability. Мany of the novel drug delivery systems are difficult to scale-up and adapt to industrial production, and one of the many benefits of ODTs is that there are ways to manufacture them with conventional technology, which makes them cost-effective. All of these advantages lead to improved patient compliance. This review discusses the advantages and disadvantages of ODTs, the available production technologies including patented technologies, the main challenges in formulation of ODTs and different approaches for solving them, and where the research into ODTs as a novel drug delivery system is headed.

Human dignity is a pivotal concept in contemporary ethical, political, and legal discourse. However, divergent and sometimes conflicting interpretations of human dignity contribute to confusion across various discussions. Given that all human beings possess inherent moral potential, each individual is endowed with universal dignity. The extent to which people develop their moral potential varies. Discussing an individual’s dignity, as in other medical specialties, cannot be separated from forensic medicine as a distinct medical discipline. In conclusion, the authors assert that establishing medical facts, or the truth ascertained through expert examination, serves justice by ensuring dignified treatment of the deceased, their family, and relatives.

Despite positive evidence for the impact of clinical pharmacy interventions on patients’ health outcome, the benefits of clinical pharmacist placed within multidisciplinary psychiatric team are still not recognized in our country. The aim of the present study was to highlight the role of clinical pharmacists in our healthcare system and evaluate the extent to which they contribute in reducing the incidence of medication-related problems (MRPs). The study included total of 82 patients hospitalized at the Department of Psychiatry at the Prilep General Hospital it the period from October 2022 to October 2023. MRPs were recognized in 70 (85.36%) patients. MRPs categories associated with medication selection (34.74%) and medication safety (16.43) followed by drug monitoring (14.55%) and patient compliance (14.08%) were found most prevalent. Clinical pharmacist made 213 recommendations (3.04 per patient). Most frequently recommended clinical interventions referred to: monitoring of laboratory parameters (9.86%), adherence to the pharmacotherapy (8.45%), prevention of use of too many medications for non-existing indication(s) or for a certain indication (7.98%) and recommendations for temporary or permanent discontinuation of medication (7.51%). Nearly 58% of all clinical pharmacist interventions aimed at preventing complications and morbidity that could arose from MRPs, of which 35% were graded as major in severity. The psychiatrists accepted 90.61% (193 of 213) of the suggested recommendations. Our findings highlight the opportunity for more targeted approaches to identifying and managing MRPs in tertiary care where tailored clinical pharmacist-led interventions may be of value. Implementation of clinical pharmacist led services, such as medication therapy management (MTM), in routine clinical practice can have a positive impact on the efficient and safe use of medicines in this patient’s group.

The migration of lead and cadmium from ceramic and glassware used for food contact is a significant source of lead and cadmium intake in humans. This study shed light on the analysis carried out to identify the presence of lead and cadmium in samples of ceramic and glassware, which are available on the market in the Republic of North Macedonia. The analysis involved examining 33 samples, consisting of 16 ceramic and 17 glass items that were subsequently categorized into three categories, following the guidelines outlined in Directive 84/500/EC and the Official Gazette of the Republic of Macedonia, no. 1/2013 for ceramics, as well as ISO 7086:2020 1, 2 for glass. An atomic absorption spectrometer (AAS) was used to analyze the concentration of lead and cadmium in samples. The obtained results indicate that the level of Pb concentration in ceramics from the second category exceeds the Maximum Permissible Migration Level (MPML). It is suspected that the lead found may have come from the lead-based paints used on the interior surfaces, as well as from the improperly applied glaze. The results also reveal that the concentration of Pb in the first category of glassware surpasses the Maximum Permissible Migration Level (MPML). It is believed that the migrated lead comes from the full exterior decoration. Upon reviewing the measured and calculated Pb values in the remaining glassware, it is evident that in all the other samples analyzed from each category, it does not surpass the values above the MPML. Additionally, Cd concentrations do not exceed the MPML in all 33 samples. Among the 33 tested samples, 10% of second-category ceramic items were found to be inadequate. This highlights the necessity for ceramics and glassware sold in the market to contain accurate declarations, particularly regarding the levels of lead and cadmium that could migrate into the food. Consumers should pay attention when purchasing such products, especially ceramics, to minimize health risks to the population.

Through the evolution, many diseases affected humans and many cures were obtained from nature. Traditional medicine recommends numerous plants and their constituents to enhance cognitive function as well as relief from depression, memory loss, and other symptoms of Alzheimer’s disease. A common problem in ethnopharmacological studies is identifying diseases from old records, either because the local culture describes the condition differently, or because the disease is unknown at that time. This is especially true at Alzheimer’s, which as a disease was identified late, thus relevant symptoms have to be identified when searching the literature like plants used in maintenance of language ability, symptoms of forgetfulness, dementia. In this manuscript, we review a subset of herbs used traditionally in Ayurveda, that supports traditional use in neurodegenerative or memory related disorders for treatment of Alzheimer’s

Information about heavy metal contamination in toys is essential to ensure the safety of the children’s product. However, 95% of the tested toys come from China, a country known for use of toy materials which are often banned in EU countries. In this paper the results from determination of three heavy metals levels (lead, cadmium and Trivalent chromium), in samples from children's toys available through specialized stores and markets in Republic of North Macedonia (RNM), are presented. The levels of lead, cadmium and Trivalent chromium in 28 samples, divided in three categories according to EN 71-3:2019, were determined using graphite furnace atomic absorption spectrometry (GF-AAS), after suitable sample preparation. The obtained results showed that the concentration of lead in the toys of the second category (purple slime and tattoo) are significantly higher than the maximum migrated limits (MML). Lead in children's toys originates from toxic lead dyes and can lead to serious health complications of central nervous system, cardiovascular, immune system and kidneys. Toys like finger paints had increased values of cadmium, but insignificantly higher compared to MML. Chromium concentrations did not exceed the MMLin all 28 toys. In summary, 14.3% of the tested toys had higher levels of the examined heavy metals than the regulatory limits. Therefore, improved quality control of children’s toys is an emerging issue to ensure consumers are purchasing safe, healthy and environmentally sustainable products.

The COVID-19 pandemic exposed significant challenges in upholding patient rights within Macedonian healthcare system. An online survey of 145 citizens assessed their perceptions regarding access to healthcare, informed consent, autonomy, and privacy during the pandemic. Results showed that 65.5% of respondents had access to essential services and 95.2% did not experience discrimination. Although 72.4% felt adequately informed about their care throughout all phases, just under half (47.6%) were aware of their healthcare and insurance rights and the procedures to secure them. Two-thirds (67.6%) reported that their autonomy was respected despite restrictive measures, and over 70% believed their privacy was maintained. These findings highlight both strengths and areas for improvement, emphasizing the need for enhanced and detailed delivery of information by healthcare professionals. Addressing these issues is crucial for refining healthcare policies and practices, ensuring equitable and effective care, and better protecting patient rights during future public health emergencies in North Macedonia.

Food labeling significantly helps consumers to make informed food choices. Considering the importance of nutrition knowledge for using food labels and making dietary decisions, the opinion of consumers on the usage of nutritional information as part of food advertising was investigated. Based on information collected via an online survey of 183 participants in the Republic of North Macedonia, this study provided consumers' perceptions and attitudes regarding food safety, brand influence, health claims, and label comprehensibility. Results of the survey indicated that while a significant percentage of respondents (48.9%) understood health claims, only 26.8% were familiar with the Nutri-Score labeling system. Brand recognition was high (96.1%), with 68.3% associating brand with product quality. Also, concerns about food safety were prevalent, with 64.8% expressing doubts about the safety of food products available at the national market. Another worrying outcome is understanding food labels, since more than half of respondents (58.8%) stated that the labels are not entirely comprehended. This study demonstrated the need for improvement of the public education on labeling systems, enhanced food safety measures, and stated apparent and more readable food labels, ultimately promoting appropriate food choices and ensuring consumer protection in the Republic of North Macedonia.

Hospital pharmacists played a crucial role during the COVID-19 pandemic, collaborating with healthcare professionals such as nurses, physicians, and respiratory therapists. They contributed to managing COVID-19 treatment protocols, ensuring adequate medication supply, and addressing shortages of essential drugs, medical devices, and personal protective equipment (PPE) by implementing conservation strategies and sourcing alternatives. A questionnaire-based study was conducted among hospital pharmacists in North Macedonia in July 2022, involving pharmacists and pharmacy technicians of various ages and experience levels from five cities, with 95.8% of respondents being female. The results highlighted the pharmacists' knowledge of COVID-19 strains, disinfectants, and current therapeutic options. The study revealed that 37.5% of participants always, 20.8% frequently, and 29.2% occasionally felt depressed or fatigued during the pandemic, though 83% never considered leaving their jobs. The survey found that 87.5% of pharmacists experienced shortages of masks, gloves, and disinfectants early in the pandemic, and 100% noted the increased cost of these supplies. Only 22.7% were not consulted for therapy advice for hospitalized COVID-19 patients. Opinions varied on the use of off-label drugs, and pharmacists played a key role in pharmacovigilance practices, with 36.4% reporting adverse events. The study confirmed the vital role of hospital in promoting of rational antibiotic use and antimicrobial resistance programs. This study was the first study conducted after the pandemics and have confirmed the pivotal role of hospital pharmacists in this period in the RN Macedonia.

Stability studies are crucial for pharmaceutical product registration, providing vital data to assess batch-to-batch consistency, monitor critical quality attributes, and ensure the product's quality, safety, and efficacy over its entire shelf life. Identifying potential issues such as potential out-of-specification (OOS) results and ensuring data quality is often facilitated by employing objective methods for trend analysis of stability data. The goal of the research was to explore the advantages of trend analysis in stability studies, highlighting its significance in forecasting OOS results and ensuring the consistent performance of pharmaceutical products within their estimated shelf life. To evaluate stability data and find the pattern of data that indicates change over time, stability studies for Lisinopril/Amlodipine tablets 20mg/10mg were subjected to trending analysis based on data from annual or routine stability studies. The trending analysis was performed to evaluate whether the data demonstrates increasing or decreasing trend (change of mean) for the stability indicating parameters over time or the data indicate no discernible change at all, as well as predicting potential OOS results during shelf life. Regression analysis as a statistical tool for trending analysis, is considered an appropriate approach to evaluating the stability data for a quantitative attribute.

Two different limulus amoebocyte lysate assays of bacterial endotoxins in parenteral solutions produced on a small scale in a clinical hospital are evaluated. The gel-clot LAL method and turbidimetric kinetic method were applied as techniques for determination of endotoxin from Gram – negative bacteria in a large volume of 0.9% NaCl solution for infusion. The same principle is applied but using different official methods for determination of bacterial endotoxin′s concertation. An overview of the advantages and disadvantages to the implementation of both methods is provided, with a detailed description of the procedures, comparison of the suitability of each method and recommendations based on the findings. The conventional gel-clot LAL method as a simple method can be recommended due to its economic sustainability in terms of equipment. On the other hand, the turbidimetric kinetic assay offers distinct advantages such as enhanced sensitivity, quantitative analysis capability, and instrumental reading. Furthermore, this method helps eliminate potential human variability in endpoint assessments. Therefore, the obtained results and critical aspects of the applied methods: the gel-clot LAL method and the turbidimetric kinetic method indicate that both LAL methods can be used for the determination of bacterial endotoxins in parenteral solutions, produced on a small scale and provide an opportunity for small laboratories to facilitate the decision – making process for choosing a method that best meets their requirements and resources.

Effective complaints management in the pharmaceutical industry is one of the cornerstones for ensuring product quality, regulatory compliance, and customer safety and satisfaction. Adequate handling of complaints ensures not only compliance with regulatory standards, but also maintenance of public confidence, the company’s reputation, and a continuous improvement of product quality. To ensure proper complaint management we must understand the importance of providing an effective complaint management system, the regulatory obligations framing it, and the processes of handling complaints, focusing on involving best practices and the potential challenges pharmaceutical companies face. This paper describes the process of handling a complaint that a pharmaceutical company has received from a foreign regulatory agency. The complaint referred to a burning sensation in the eyes after applying an eye ointment containing 1% chloramphenicol and a change in the smell of the ointment. After conducting an extensive investigation, the quality of the product was confirmed and it was demonstrated that there is no risk to patient health.

Proteins are macromolecular compounds made up of amino acids linked by peptide bonds. They are the basic structural component of all living organisms. Their diversity has to do with their structure, and therefore with the way the amino acid residues are arranged in the molecule. Albumin shape is determined by the sequence of amino acids that make it up. The primary amino acid in its composition is cysteine and in smaller amounts glycine, methionine and one tryptophan residue, thanks to which it exhibits fluorescent properties. For structural studies of proteins, many physical methods are used. The most commonly chosen are spectroscopic methods, which deal with the interaction between electromagnetic radiation and matter. The article provides an overview of spectroscopic methods employed in the structural studies of proteins. It also serves as a prelude to further research that aims to utilise one of the spectroscopic methods to study the structural changes of albumin after exposure to physicochemical agents. The described spectroscopic methods are characterized by different sensitivity, specificity and procedures to be performed during sample preparation for the study. In the spectroscopic study of proteins, with particular attention to changes in their structure, the method of fluorescence spectroscopy deserves attention. It is the best choice for studying structural changes in proteins that occur under the influence of physicochemical factors. Capturing these changes and relating them to the functions of proteins enriches the knowledge of the normal functioning of the body, as well as the basis of some diseases.

Introduction: Phimosis is a disease entity that society has given negative connotations. Discussions about the foreskin, both in the context of its pathological and physiological conditions have been going on for centuries, and include issues related to religion, hygiene, esthetics and tradition. In 2002, researchers from London recognised that secondary phimosis corresponds to lichen sclerosus et atrophicus, better known as balanitis xerotica obliterans (BXO), constituting it the only absolute indication for circumcision in boys. This study aims to assess the histopathological examinations of patients after the surgical treatment of phimosis in order to ascertain the relationship between BXO and clinically diagnosed phimosis. Material and methods: This study analyzed the results of histopathological examinations in patients who underwent surgical methods of phimosis treatment in the period from January 2014 to March 2020. The inclusion criteria of the study were the surgical treatment of phimosis with the accompanying histopathological examination of the specimens collected during the surgery. The data were collected prospectively and randomly. Results: There were 106 patients in whom a surgical procedure and histopathological examination were performed. The mean age of the patients was 9.41 ± 3.82 years. In the entire group of patients, the diagnosis of BXO (including BXO focal) was 59% (n = 63). Conclusions: The most common cause of secondary phimosis after surgical treatment is BXO, with a patient prevalence ranging from 5.5% to 84%. The results of this study fall within this range. Visible scarring of the foreskin may also be caused by other factors such as chronic inflammation of the foreskin, but also poor hygiene or infections in this area.

Introduction: Chronic diseases are one of the most serious phenomena and problems in the modern world. These include: asthma, allergies and arterial hypertension (hypertension). Even short-term exposure to polluted air increases the incidence of both hypertension and asthma. The aim of the study is to determine the relationship between the level of selected atmospheric air pollutants in the city of Bielsko-Biała in the years 2018–2022 (nitrogen dioxide, suspended dust PM2.5 and PM10 and benzo(a)pyrene) and the incidence of asthma and hypertensive disease among children and youth from 0 to 18 years of age in Bielsko-Biała. Material and methods: Based on data from the Health Department – the Silesian Voivodeship Office in Katowice regarding the incidence of asthma and hypertensive disease, tables and graphs illustrating the incidence of these diseases were prepared. The annual average concentrations of selected air pollutants were also taken into account. Based on the Statistica program and Pearson correlation coefficients, the relationship between the occurrence of asthma, hypertensive disease and air pollution was examined. Results: The incidence of hypertension and asthma among children and adolescents in Bielsko-Biała is decreasing and amounted to 32.1/10,000 in 2018 and 18.7/10,000 in 2022 in the case of hypertensive disease, and 394.8/10,000 in 2018 and 319.9/10,000 in 2022 for asthma. The average annual concentration of PM10 and benzo(a)pyrene is also decreasing. Conclusions: In the discussed period, the average annual concentrations of the analyzed substances were not exceeded. The decreasing incidence of both asthma and hypertension is related to the improvement in atmospheric air quality.

Introduction: Until now, there has been little work on the association of keratoconus with psychiatric disorders. None of these address the role of ego-resiliency, which may prove crucial in coping with chronic illness. Material and methods: 74 participants with keratoconus and 92 without this diagnosis participated in the study. The respondents were surveyed using a toolkit: the ER-89 questionnaire for ego-resiliency, the State Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and the Inventory for Personality Disorders according to DSM-IV (IBZO-DSM-IV). Statistical analyses were performed using Statistica 13.3 software. Results: A statistically significant negative regression of optimal regulation (OR) as a component of ego-resiliency (ER) in light of avoidant personality, dependent personality, depression intensity on the HDRS, and both trait and anxiety status was evident in both the study and control groups. No statistically significant differences in ER intensity were evident between the study and control groups. Conclusions: Ego-resiliency reduces the intensity of anxiety and depression symptoms as well as the intensity of dependent and avoidant personality traits. Patients with keratoconus do not differ in the intensity of ego-resiliency from those without the condition.