Background: The concurrent Zika Virus (ZIKV) outbreaks in the United States and Northeast Brazil have evoked global surveillance. Zika infection has been correlated with severe clinical symptoms, such as microcephaly, Guillain-Barré syndrome, and other congenital brain abnormalities. Recent data suggest that ZIKV predominantly targets neural progenitor cells leading to neurological impairment. Despite the clinical evidence, detailed experimental mechanism of ZIKV neurotropic pathogenesis has not been fully understood yet. Here we hypothesized that ZIKV produces miRNAs, which target essential host genes involved in various cellular pathways facilitating their survival through immune evasion and progression of disease during brain development.Methods: From genome sequence information using several bioinformatic tools, we predicted pri-miRNAs, pre-miRNAs, and finally the mature miRNAs produced by ZIKV. We also identified their target genes and performed functional enrichment analysis to identify the biological processes associated with these genes. Finally, we analyzed a publicly available RNA-seq data set to determine the altered expression level of the targeted genes.Results: From ZIKV genome sequence, we identified and validated 47 putative novel miRNAs. Functional enrichment of the targeted genes demonstrates the involvement of various biological pathways regulating cellular signaling, neurological functions, cancer, and fetal development. The expression analysis of these genes showed that ZIKV-produced miRNAs downregulate the key genes involved in these pathways, which in turn may lead to impaired brain development.Conclusions: Our finding proposes novel ZIKV miRNAs and their targets, which upon experimental validation could help developing new therapeutics to combat ZIKV infection and minimize ZIKV-mediated pathologies.

The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formulations meet the FDA criteria to assume bioequivalence. Twenty-four healthy volunteers were enrolled into this randomized, single-dose, 2-way crossover, open-label pharmacokinetic study. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa as a single dose of 60 mg tablets after 12 h overnight fasting, with a washout period of two weeks. Following oral administration, blood samples were collected at 0 (baseline), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0, and 120.0 h. Serum concentration of etoricoxib was assessed using a high performance liquid chromatographic-UV spectrometry procedure. The pharmacokinetic parameters were determined by the non-compartmental method. After administering a single dose of 60 mg of each etoricoxib formulation, the obtained mean (SD) values for the test and reference products were 1.26 (0.33) and 1.29 (0.35) microg/ml for Cmax; 3.25 (2.64) and 2.63 (1.40) h for t(max); 29.63 (8.31) and 30.40 (5.85) h x microg/ml for AUC0-120; and 31.84 (10.97) and 33.00 (8.10) h x microg/ml for AUC0-infinity, respectively. The mean t1/2 was found 27.99 (7.87) h and 29.84 (7.93) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. After analysis of variance, no period, sequence or formulation effects were observed for any pharmacokinetic property. The 90% confidence intervals of the test/reference mean ratios of the 1n-transformed AUC0-120, AUC0-infinity and Cmax mean values were 95.90% (85.37%-107.74 %), 94.69% (84.43%-106.20%) and 97.87% (85.54 %-111.98 %), respectively, which fell within the predetermined FDA bioequivalence range of 80%-125%. This single-dose study found that the test and reference formulations of etoricoxib met the regulatory criteria for bioequivalence in terms of both rate and extent of absorption.

This study demonstrates the absence of common CYP3A4 variant alleles in Nepalese people residing in Bangladesh whereas Nepalese people carrying the CYP3A5*1/*1 genotype appear to show a significantly higher 6β-hydroxycortisol/cortisol ratios compared to those with CYP3A5*3/*3 genotype.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive lung disease that leads to gradual decline in lung function. The molecular mechanism and risk factors of this disease are still obscure. Poorly understood etiology of this disease is the major obstacle in the identification of potential biomarkers and drug targets. In this study, microarray gene expression data of normal and IPF patient has been utilized for the statistical analysis of differentially expressed genes (DEGs) with a view to identifying potential molecular signatures using network-based system. Then their functional enrichment analysis revealed their predominant involvement in transcription, protein acetylation, extracellular matrix organization, apoptic process, inflammatory response etc. Protein-Protein Interaction (PPI) network revealed (UBC, PTEN, SOS1, PTK2, FGFR1, YAP1, FOXO1, RACK1, BMP4 and CD44) as hub proteins in IPF. Subsequent regulatory network analysis suggested (E2F1, STAT3, PPARG, MEF2A, FOXC1, GATA3, YY1, GATA2, NFKB1, and FOXL1) as the best regulatory transcriptional signatures and (hsa-mir-155-5p, hsa-mir-16-5p, hsa-mir-17-5p, hsa-mir-19a-3p, hsa-mir-192-5p, hsa-mir-92a-3p, hsa-mir-26b-5p, hsa-mir-335-5p, hsa-mir-124-3p, and hsa-let-7b-5p) as the best post-transcriptional signatures. This study represents proteome and RNA signatures of IPF which might be useful to uphold the present efforts in the discovery of potential biomarkers and treatments of this disease.

Vitex peduncularis (Verbenaceae), a perennial tree, is locally utilized for possessing multifaceted pharmacological properties including analgesic, antimalarial, anti-angina, antidiabetic, antioxidant, anti-inflammatory and hepatoprotective. Hence, this study aims to evaluate their antioxidant, thrombolytic, cytotoxic and antibacterial activities from the methanolic crude extract and its various solvent fractions. Data from antioxidant and thrombolytic assay displayed that Kupchan partitioned chloroform soluble fraction revealed the maximum phenolic content (73.39 mg of GAE/g of extract), DPPH free radical scavenging activity (26.69 μg/ml) and thrombolytic activity (37.35%). In brine shrimp lethality evaluation, the LC50 values indicate that the most cytotoxic compound was found to be from ethyl acetate soluble fraction (LC50 6.73 μg/ml). Finally, antibacterial activity of different fractions showed that both chloroform and methanolic fraction possessed mild activity against the tested bacteria. The potential biological effects of the crude fractions have been demonstrated demanding future studies of the isolated compounds to assess these activities. Bangladesh J. Sci. Ind. Res. 57(4), 239-246, 2022