• Pratt Levin opublikował 5 miesięcy, 1 tydzień temu

    The incidence of hospital- and community-acquired infections has been dramatically increased worldwide. Accordingly, hands hygiene and the use of disinfectants have been increased leading to the expansion in hand sanitizers production to meet public demand. This study was conducted to assess the efficiency of common disinfectants in the market of Riyadh, Saudi Arabia in inhibiting the microbial growth during the time of Coronavirus disease 2019 (COVID-19) pandemic. Five bacterial strains of commonly hospital-acquired infections (Pseudomonas aeruginosa, Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, and Enterococcus faecalis) (ATCC reference strains and clinical isolates) were examined for their susceptibility against 18 disinfectants collected from the Saudi market. The tested 18 disinfectants were broadly clustered into different groups based on their active chemical composition as following 12 products contained alcohol, 2 products had chlorhexidine, 3 products contained mixed concentration of alcohol/chlorhexidine and 1 product had a mixture of chlorhexidine/Hexamidine/Chlorocresol. By measuring the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), our results revealed that all the 18 disinfectants have reduced the microbial growth of all the tested strains. Generally, the MICs and the MBCs for the clinical strains are higher than those of the reference strains. Taken together, our findings showed that all tested products have high disinfectants’ killing rate against microbes of different origins, which suggest the high quality of these disinfectants and the good surveillance practice by the local authorities in Saudi Arabia.Soil-transmitted helminth (STH) infections cause significant morbidity in children and women of reproductive age. The World Health Organization (WHO) recommends preventive chemotherapy (PC) of at-risk populations with anthelminthics to control these infections. Historically, STH are very intensively transmitted in Pemba Island (Zanzibar). A survey conducted in 1994 in 12 schools estimated a STH prevalence near to 100%. This extremely high prevalence induced the introduction of PC in the island; initially, however, PC was not regularly administered because of difficulties linked to drug procurement. A second STH survey, conducted in 2011, in 24 schools estimated a prevalence of STH of 89%; after this survey, PC was regularly administered until 2018. We conducted a survey in 2021 using the same method as that used in 2011. The prevalence of STH was evaluated at 80% (95% CI 78.1-81.5) and most of the STH cases were due to Trichuris trichiura. More than 32% (95% CI 30.3-34.0) of the children investigated had infections of moderate or heavy intensity. PC has been conducted for over 25 years in Pemba Island. However, despite its beneficial impact, both the prevalence and the intensity of STH infections remain high, and the intervention has been insufficient in controlling STH morbidity. This is probably due to a combination of irregular PC, climatic conditions favourable to STH transmission, the low sensitivity of T. trichiura to benzimidazoles, high population density and poor sanitation. Improvement of sanitation coverage remains a key measure to permanently reduce the prevalence and intensity of STH. Possible changes to the present PC approaches to better control STH in Pemba would be (i) to assure high coverage in all schools, (ii) to use mebendazole instead of albendazole given its better activity on T. trichiura and (iii) to use a combination of ivermectin and mebendazole to further increase anthelminthic efficacy on T. trichiura.Death-associated protein kinase 3 (DAPK3) is a serine/threonine protein kinase that regulates apoptosis, autophagy, transcription, and actin cytoskeleton reorganization. DAPK3 induces morphological alterations in apoptosis when overexpressed, and it is considered a potential drug target in antihypertensive and anticancer drug development. In this article, we report new findings from a structure-guided virtual screening for discovery of phytochemicals that could modulate the elevated expression of DAPK3, and with an eye to anticancer drug discovery. We used the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT), a curated database, as part of the methodology. The potential initial hits were identified based on their physicochemical properties and binding affinity toward DAPK3. Subsequently, various filters for drug likeness followed by interaction analysis and molecular dynamics (MD) simulations for 100 nsec were performed to explore the conformational sampling and stability of DAPK3 with the candidate molecules. Notably, the data from all-atom MD simulations and principal component analysis suggested that DAPK3 forms stable complexes with ketanserin and rotenone. In conclusion, this study supports the idea that ketanserin and rotenone bind to DAPK3, and show stability, which can be further explored as promising scaffolds in drug development and therapeutics innovation in clinical contexts such as hypertension and various types of cancer.The interplay between N6-methyladenosine (m6A) modification and microRNAs (miRs) participates in cancer progression. This study is conducted to explore the role of miR-19a-3p in nasopharyngeal carcinoma (NPC) cell proliferation and invasion. Reverse transcription quantitative polymerase chain reaction and Western blot showed that miR-19a-3p was upregulated in NPC tissues and cells and related to poor prognosis, methyltransferase-like 3 (METTL3) was highly expressed, whereas BMP and activin membrane-bound inhibitor (BAMBI) was weakly expressed in NPC tissues and cells. miR-19a-3p downregulation inhibited cell proliferation and invasion, whereas miR-19a-3p overexpression played the opposite role. m6A quantification and m6A RNA immunoprecipitation assays showed that METTL3-mediated m6A modification promoted the processing and maturation of pri-miR-19a via DiGeorge syndrome critical region gene 8 (DGCR8). Dual-luciferase assay showed that BAMBI was a target of miR-19a-3p. The rescue experiments showed that BAMBI downregulation reversed the role of miR-19a-3p inhibition in NPC cells. A xenograft tumor model showed that METTL3 downregulation inhibited tumor growth via the miR-19a-3p/BAMBI in vivo. Overall, our findings elicited that METTL3-mediated m6A modification facilitated the processing and maturation of pri-miR-19a via DGCR8 to upregulate miR-19a-3p, and miR-19a-3p inhibited BAMBI expression to promote NPC cell proliferation and invasion, thus driving NPC progression.Fibro-adipogenic progenitor cells (FAPs) are a population of stem cells in skeletal muscle that play multiple roles in muscle repair and regeneration through their complex secretome; however, it is not well understood how the FAP secretome is altered with muscle disuse atrophy. Previous work suggests that the inflammatory cytokine IL-1β is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1β secretion are also known to stimulate the release of extracellular vesicles (EVs). Here, we examined the microRNA (miRNA) cargo of FAP-derived, platelet-derived growth factor receptor A (PDGFRα+) EVs from hindlimb muscles of wild-type and IL-1β KO mice after 14 days of single-hindlimb immobilization. Hindlimb muscles were isolated from mice following the immobilization period, and PDGFRα+ extracellular vesicles were isolated using size-exclusion chromatography and immunoprecipitation. Microarrays were performed to detect changes in miRNAs with unloading and IL-1β deficiency. Results indicate that the PDGFRα+, FAP-derived EVs show a significant increase in miRNAs, such as miR-let-7c, miR-let-7b, miR-181a, and miR-124. These miRNAs have previously been demonstrated to play important roles in cellular senescence and muscle atrophy. Furthermore, the expression of these same miRNAs was not significantly altered in FAP-derived EVs isolated from the immobilized IL-1β KO. These data suggest that disuse-related activation of IL-1β can mediate the miRNA cargo of FAP-derived EVs, contributing directly to the release of senescence- and atrophy-related miRNAs. Therapies targeting FAPs in settings associated with muscle disuse atrophy may therefore have the potential to preserve muscle function and enhance muscle recovery.Cytokines mediate T-helper (TH) responses that are crucial for determining the course of infection and disease. The expression of cytokines is regulated by transcription factors (TFs). Here we present the frequencies of single nucleotide polymorphisms (SNPs) in cytokine and TF genes in a Zimbabwean population, and further relate SNPs to susceptibility to schistosomiasis and cytokine levels. Individuals (N = 850) were genotyped for SNPs across the cytokines IL4, IL10, IL13, IL33, and IFNG, and their TFs STAT4, STAT5A/B, STAT6, GATA3, FOXP3, and TBX21 to determine allele frequencies. Circulatory levels of systemic and parasite-specific IL-4, IL-5, IL-10, IL-13, and IFNγ were quantified via enzyme-linked immunosorbent assay. Schistosoma haematobium infection was determined by enumerating parasite eggs excreted in urine by microscopy. SNP allele frequencies were related to infection status by case-control analysis and logistic regression, and egg burdens and systemic and parasite-specific cytokine levels by analysis of variance and linear regression. Novel findings were i) IL4 rs2070874*T’s association with protection from schistosomiasis, as carriage of ≥1 allele gave an odds ratio of infection of 0.597 (95% CIs, 0.421-0.848, p = 0.0021) and IFNG rs2069727*G’s association with susceptibility to schistosomiasis as carriage of ≥1 allele gave an odds ratio of infection of 1.692 (1.229-2.33, p = 0.0013). Neither IL4 rs2070874*T nor IFNG rs2069727*G were significantly associated with cytokine levels. This study found TH2-upregulating SNPs were more frequent among the Zimbabwean sample compared to African and European populations, highlighting the value of immunogenetic studies of African populations in the context of infectious diseases and other conditions, including allergic and atopic disease. In addition, the identification of novel infection-associated alleles in both TH1- and TH2-associated genes highlights the role of both in regulating and controlling responses to Schistosoma.The prevalence of allergic diseases is on the rise, yet the environmental factors that contribute to this increase are still being elucidated. Laundry detergent (LD) that contains cytotoxic ingredients including microbial enzymes continuously comes into contact with the skin starting in infancy. An impaired skin barrier has been suggested as a route of allergic sensitization. We hypothesized that exposure of skin to LD damages the skin barrier resulting in systemic sensitization to allergens that enter through the impaired skin barrier. Mouse skin samples exposed in vitro to microbial proteases or LD exhibited physical damage, which was more pronounced in neonatal skin as compared to adult skin. Exposure of the skin to microbial proteases in vitro resulted in an increase in the levels of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). BALB/c wild type mice epicutaneously exposed to LD and ovalbumin (OVA) showed an increase in levels of transepidermal water loss, serum OVA-specific immunoglobulin (Ig) G1 and IgE antibodies, and a local increase of Il33, Tslp, Il4 and Il13 compared with LD or OVA alone.

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