001) for 12 h compared with unprotected control, a threefold reduction in the attack. In outdoor trials, TFT-PET provided only 16% protection against An. harrisoni Harbach & Manguin (Diptera Culicidae) compared with unprotected collector (P = 0.0213). The TFT-PET vest reduced nonanophelines landing by 1.4-fold compared with the PET control with a 29% protective efficacy. These findings suggest that TFT-PET had diminished protective efficacy in an open field environment.  https://www.selleckchem.com/products/heparan-sulfate.html  Nonetheless, the concept of a wearable TFT emanatory device has the potential for protecting against outdoor biting mosquitoes. Further development of portable SR tools is required, active ingredient selection and dose optimization, and more suitable device design and materials for advancing product feasibility.Cutaneous leishmaniasis is an important parasitic and vector-borne disease in Iran and can be transmitted to humans and animals through bites of infected female sand flies. The present study aimed to determine the pooled prevalence of Leishmania major in sand flies in Iran. A systematic review and meta-analysis was performed in the present study, so that databases, namely PubMed, Web of Sciences, Science Direct, ProQuest, Embase, Cochrane Reviews, and Scopus as well as IranDoc, SID, Elmnet, and Magiran were searched for finding Persian articles. Inclusion criteria of study contained the study in Iran and investigation of L. major parasite in sand flies. The quality of studies was examined by Joanna Briggs Institute Critical Appraisal Checklist for studies that reported prevalence data; and the data were analyzed by Stata 14 software. In total, 42 studies were evaluated, all of which had investigated the infection of Phlebotomus papatasi Scopoli (Diptera Psychodidae). The infection of Phlebotomus caucasicus group was investigated in 13 studies, Phlebotomus ansarii Lewis in four studies, Phlebotomus salehi Mesghali and Rashti in five studies, and the infection of other species of sandflies in seven studies. According to the meta-analysis, the pooled prevalence of Ph. papatasi, Ph. caucasicus group, Ph. salehi, and Ph. ansarii were equal to 2.4, 6.2, 1.6, and 9.2%, respectively, with 95% confidence interval. According to reports of different rates of sand fly infection in different regions, all studies should have certain and standard forms and formats to determine the pooled prevalence of sand fly infection.Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Reliable and translational biomarkers are needed for early detection of DILI. microRNAs (miRNAs) have received wide attention as a novel class of potential DILI biomarkers. However, it is unclear how DILI drugs other than acetaminophen may influence miRNA expression or which miRNAs could serve as useful biomarkers in humans. We selected ketoconazole (KCZ), a classic hepatotoxin, to study miRNA biomarkers for DILI as a proof of concept for a workflow that integrated in vivo, in vitro, and bioinformatics analyses. We examined hepatic miRNA expression in KCZ-treated rats at multiple doses and durations using miRNA-sequencing and correlated our results with conventional DILI biomarkers such as liver histology. Significant dysregulation of rno-miR-34a-5p, rno-miR-331-3p, rno-miR-15b-3p, and rno-miR-676 was associated with cytoplasmic vacuolization, a phenotype in rat livers with KCZ-induced injury, which preceded the elevation of serum liver transaminases (ALT and AST). Between rats and humans, miR-34a-5p, miR-331-3p, and miR-15b-3p were evolutionarily conserved with identical sequences, whereas miR-676 showed 73% sequence similarity. Using quantitative PCR, we found that the levels of hsa-miR-34a-5p, hsa-miR-331-3p, and hsa-miR-15b-3p were significantly elevated in the culture media of HepaRG cells treated with 100 µM KCZ (a concentration that induced cytotoxicity). Additionally, we computationally characterized the miRNA candidates for their gene targeting, target functions, and miRNA/target evolutionary conservation. In conclusion, we identified miR-34a-5p, miR-331-3p, and miR-15b-3p as translational biomarker candidates for early detection of KCZ-induced liver injury with a workflow applicable to computational toxicology studies.Exposure to tolvaptan is associated with a significant risk of liver injury in a small fraction of patients with autosomal dominant polycystic kidney disease. The observed delayed onset of liver injury of between 3 and 18 months after commencing tolvaptan treatment, along with rapid recurrence of symptoms following re-challenge is indicative of an adaptive immune attack. This study set out to assess the intrinsic immunogenicity of tolvaptan and pathways of drug-specific T-cell activation using in vitro cell culture platforms. Tolvaptan (n = 7), as well as oxybutyric (DM-4103, n = 1) and hydroxybutyric acid (DM-4107, n = 18) metabolite-specific T-cell clones were generated from tolvaptan naive healthy donor peripheral blood mononuclear cells. Tolvaptan and DM-4103 T-cell clones could also be activated with DM-4107, whereas T-cell clones originally primed with DM-4107 were highly specific to this compound. A signature cytokine profile (IFN-γ, IL-13, granzyme B, and perforin) for almost all T-cell clones was identified. Mechanistically, compound-specific T-cell clone activation was dependent on the presence of soluble drug and could occur within 4 h of drug exposure, ruling out a classical hapten mechanism. However, antigen processing dependence drug presentation was indicated in many T-cell clones. Collectively these data show that tolvaptan-associated liver injury may be attributable to an adaptive immune attack upon the liver, with tolvaptan- and metabolite-specific T cells identified as candidate effector cells in such etiology.Protease-activated receptor (PAR)-1 has emerged as a key profibrotic player in various organs including kidney. PAR-1 activation leads to deposition of extracellular matrix (ECM) proteins in the tubulointerstitium and induction of epithelial-mesenchymal transition (EMT) during renal fibrosis. We tested the anti-fibrotic potential of vorapaxar, a clinically approved PAR-1 antagonist for cardiovascular protection, in an experimental kidney fibrosis model of unilateral ureteral obstruction (UUO) and an AKI-to-chronic kidney disease (CKD) transition model of unilateral ischemia-reperfusion injury (UIRI), and dissected the underlying renoprotective mechanisms using rat tubular epithelial cells. PAR-1 is activated mostly in the renal tubules in both the UUO and UIRI models of renal fibrosis. Vorapaxar significantly reduced kidney injury and ameliorated morphologic changes in both models. Amelioration of kidney fibrosis was evident from down-regulation of fibronectin (Fn), collagen and α-smooth muscle actin (αSMA) in the injured kidney.