BioMed Research International最新文献

Background and Purpose: The continuous accumulation of M2 macrophages may potentially contribute to the development of kidney fibrosis in chronic kidney disease (CKD). The purpose of this study was to analyze the infiltration of M2 macrophages in uremic patients and to seek new strategies to slow down the progression of renal fibrosis. Methods: We conducted a comprehensive search for expression data pertaining to uremic samples within the Gene Expression Omnibus (GEO) database, encompassing the time frame from 2010 to 2022. Control and uremic differentially expressed genes (DEGs) were identified. Immune cell infiltration was investigated by CIBERSORT and modules associated with M2 macrophage infiltration were identified by weighted gene coexpression network analysis (WGCNA). Consistent genes were identified using the least absolute shrinkage and selection operator (LASSO) and selection and visualization of the most relevant features (SVM-RFE) methods to search for overlapping genes. Receiver operating characteristic (ROC) curves were examined for the diagnostic value of candidate genes. Quantitative real-time PCR (qPCR) examined the expression levels of candidate genes obtained from uremic patients in M2 macrophage. Results: A total of 1298 DEGs were identified within the GSE37171 dataset. Significant enrichment of DEGs was observed in 20 biological processes (BP), 19 cellular components (CC), 6 molecular functions (MF), and 70 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. CIBERSORT analysis observed a significant increase in B-cell memory, dendritic cell activation, M0, M1, M2, and plasma cell numbers in uremic samples. We identified the 10 most interrelated genes. In particular, adenomatous polyposis coli (APC) and zinc finger and BTB structural domain 2 (ZBTB2) were adversely associated with the infiltration of M2 macrophages. Importantly, the expression levels of APC and ZBTB2 were far lower in M2 macrophages from uremic patients than those in healthy individuals. Conclusion: The development of renal fibrosis may be the result of M2 macrophage infiltration promoted by APC and ZBTB2.

Biofilm formation by Staphylococcus aureus is a major challenge in clinical settings due to its role in persistent infections. The AgrA protein, a key regulator in biofilm development, is a promising target for therapeutic intervention. This study investigates the antibiofilm potential of halogenated phenazine compounds by targeting AgrA and explores their molecular interactions to provide insights for drug development. We employed molecular docking, molecular dynamics simulations, and computational mutagenesis to evaluate the binding of halogenated phenazine compounds (C1 to C7, HP, and HP-14) to AgrA. Binding free energy analysis was performed to assess the affinity of these compounds for the AgrA-DNA complex. Additionally, the impact of these compounds on AgrA's structural conformation and salt bridge interactions was examined. The binding-free energy analysis revealed that all compounds enhance binding affinity compared to the Apo form of AgrA, which has a ΔG_bind of -80.75 kcal/mol. The strongest binding affinities were observed with compounds C7 (-113.84 kcal/mol), HP-14 (-115.23 kcal/mol), and HP (-112.28 kcal/mol), highlighting their effectiveness. Molecular dynamics simulations demonstrated that these compounds bind at the hydrophobic cleft of AgrA, disrupting essential salt bridge interactions between His174-Glu163 and His174-Glu226. This disruption led to structural conformational changes and reduced DNA binding affinity, aligning with experimental findings on biofilm inhibition. The halogenated phenazine compounds effectively inhibit biofilm formation by targeting AgrA, disrupting its DNA-binding function. The study supports the potential of these compounds as antibiofilm agents and provides a foundation for rational drug design targeting the AgrA-DNA interaction. Future research should focus on further optimizing these lead compounds and exploring additional active sites on AgrA to develop novel treatments for biofilm-associated infections.

Background: Access to cardiovascular medications is severely hampered by their unavailability and high cost, particularly for the poorest households in developing nations. The availability and price range of cardiovascular medications are significantly limited in both hospital and community pharmacies. Objectives: The aim of this study is to assess the availability and price variations of commonly used cardiovascular medicines in hospital pharmacies in Gondar Town, northwest Ethiopia. Methods: From July 13 to August 6, 2022, a mixed cross-sectional and simulated client survey was carried out at two hospital and 13 community pharmacies in Gondar Town. The analysis and data entry were performed using SPSS Version 25 and EpiData Version 4.2, respectively. The availability and pricing variations of the medications are given as percentages. The significance was examined using paired t tests. Results: On average, community retail pharmacies offered 33.22% of CVD drugs. Aspirin (81 mg), amlodipine (5 mg), atorvastatin (20 mg), and hydrochlorothiazide (25 mg) were the most readily available drugs in community pharmacies. Overall, 28.00% of the hospital pharmacies had available CVD medicines during the course of our analysis. The average cost for the 25 CVD medications in hospital pharmacies was $0.699, with a standard deviation (SD) of 1.513, which was less than the cost at community pharmacies ($2.741 with an SD of 6.015) (p = 0.045). Conclusion: CVD medications were more available in community pharmacies than in hospital pharmacies, although there were fewer CVD medications available than recommended by the WHO/HAI (80%) in both hospital and community pharmacies. There was a statistically significant difference between the two prices. Compared to that at hospital pharmacies, the mean price at community pharmacies was greater.

Intestinal parasitic infections (IPIs) remain a significant contributor to morbidity and mortality globally, particularly in developing countries such as Ethiopia. Periodic assessments of IPI prevalence are essential prerequisite for effective control measures. Therefore, this cross-sectional study is aimed at determining the prevalence of gastrointestinal parasitic infections and associated risk factors among schoolchildren at Wonji Shoa Secondary School, East Shoa Zone, Adama district, Oromia region, Ethiopia, between January and June 2022. A simple random stratified sampling technique was employed to select participants. Sociodemographic and risk factor data were collected using a structured questionnaire. Stool samples were examined to identify parasites. Data were analyzed using SPSS version 20. Descriptive statistics, chi-square tests, and logistic regression were conducted to assess associations between variables and then the strength of the association. A p value < 0.05 was considered statistically significant. Of the 403 selected students, 330 completed the study that makes 81.89% response success. The overall IPI prevalence was 16.66% (55/330), with a higher prevalence among males (60%, 33/55) than females (40%, 22/55). Five parasite species were identified: two protozoa (Entamoeba histolytica and Giardia lamblia) with a combined prevalence of 9.70% (32/330) and three helminths (Ascaris lumbricoides, Hymenolepis nana, and Taenia spp.) with a combined prevalence of 6.97% (23/330). Cysts were detected in 62.5% of E. histolytica cases (15/24), and eggs were detected in 76.92% of A. lumbricoides cases (10/13). The study revealed a substantial IPI prevalence (16.66%) among the students. This finding underscores the need for effective prevention and control strategies. The predominance of parasitic infections among males is notable requiring further investigation of the factors. The identification of multiple parasite species indicates a complex epidemiological scenario. The presence of protozoan cysts and helminthic eggs highlights the potential for fecal-oral transmission and the importance of improved sanitation and hygiene practices.

Ricinodendron heudelotii is a plant of the Euphorbiaceae family, used in traditional medicine to treat numerous diseases, including high blood pressure. The aim of this study is to evaluate the antioxidant and vasorelaxant effects of the aqueous extract of the stem bark of R. heudelotii. The pharmacological studies were carried out using the aqueous extract obtained by infusion. The antioxidant capacity of R. heudelotii was assessed by in vitro tests with DPPH (2,2-diphenyl-1-picryl-hydrazyl), ABTS (2,2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid), iron-reducing capacity (FRAP), and inhibition of nitric oxide (NO) release. In vitro studies, the aortic rings obtained from adult Wistar albino rats of both sexes were used to determine the vasorelaxant effects of the extract of R. heudelotii on the NO and prostacyclin (PGI2) pathways as well as its involvement on various potassium channels were determined on intact or naked fragments of rat aorta precontracted with phenylephrine (10^-6 M) or KCl (60 mM). The aqueous extract of R. heudelotii exhibited a remarkable DPPH (EC₅₀: 1.68 μg/mL) and ABTS (EC₅₀: 106.30 μg/mL) and nitric oxide (53.71% inhibition at 1000 μg/mL) radical scavenging activities as well as reducing power (absorbance of 1.56 at 1000 μg/mL). The nitric oxide inhibitor, N_G-nitro-L-arginine methyl ester (L-NAME), and prostacyclin inhibitor, indomethacin, significantly attenuated the vasodilatory effect of R. heudelotii. Tetraethylammonium could not inhibit the vasodilatory effect of the extract, unlike glibenclamide and barium chloride. Ricinodendron heudelotii extract possesses antioxidant properties and vasorelaxing effect linked to endothelium-related factors, and this relaxation was partially mediated mainly through the inhibition of K_ir and K_ATP channels.

Background: Paracetamol, also known as acetaminophen, is categorized as an analgesic and antipyretic medication and is available as over the counter (OTC) medication. It is commonly used in conditions associated with pain and fever. There is a tendency for community to prefer using imported paracetamol tablets from Europe and United States than from Asia and Africa worrying of the quality of the products. Safety, effectiveness, and efficacy of a medicine can be guaranteed when its quality is reliable; however, there is limited data on the quality of locally manufactured paracetamol tablets, thus necessitating this study. Aim: This study is aimed at assessing the quality of paracetamol tablets 500 mg manufactured by local companies by evaluating their physical parameters, assay results, and dissolution profiles. The compliance of these tablets with the specifications outlined in the British Pharmacopoeia (BP) was analyzed. Additionally, a comparative dissolution test was conducted to assess dissolution profile for innovator product and generics. Method: Five different brands from East African countries with 76 tablets from each brand were compared with the innovator product regarding weight variation, hardness, friability, assay, and dissolution test based on the BP specifications. Results and discussion: All samples of paracetamol tablets 500 mg from the local manufacturers in this study met the specifications set by the BP for physical parameters, including weight variation, friability, hardness, and disintegration tests. The weight variation test, directly related to drug content variation, demonstrated compliance within the acceptable deviation of 5%. Similarly, the assay test, which determines the concentration of the active pharmaceutical ingredient (API), confirmed that all samples complied with the acceptable concentration range of 90%-110% for paracetamol. The dissolution test, assessing the percentage release of the API within a specified time, demonstrated that at 15 min, two samples (diodol and enamol) exhibited lower concentration releases than the required 80%, indicating potential delays in their bioavailability and onset of action. Conclusion: To conclude, all samples had good quality and they can be used for their therapeutic purposes.