In vitro study was carried out in an important medicinal plant Tinospora cordifolia (Willd.) Miers belonging to the family Menispermaceae.Vegetative parts such as stem, leaf and nodal explants were excised from an elite in vivo grown mature plant and thereafter cultured on Murashige-Skoog (MS) medium supplemented with different hormonal concentrations for callus induction and organogenesis. Callus formation occurred from nodal segments, leaf and inter-node explants when planted on different combinations of hormones. Tinospora cordifolia showed response for in vitro shoot growth from the nodal segment. The best shoot growth was observed on MS medium supplemented with kinetin (1.5 mg/l). Similarly, the best result for root induction was obtained on MS medium supplemented with 6-benzylaminopurine (1.0 mg/l) and naphthaleneacetic acid (2.5 mg/l).

Exosomes are small extracellular vesicles secreted by cells and have a major role in cell-to-cell signaling. As dengue infection progresses from a mild to a severe form of infection, the exosome's microRNA (miRNA) composition might change, which may contribute to pathogenesis. In this study, a comprehensive analysis of serum exosomal miRNAs was performed and their involvement in dengue virus-induced disease progression in an Indian cohort was assessed. Small RNA-seq showed 50 differentially expressed exosomal miRNAs that were significantly dysregulated during dengue infection. After extensive validation, miR-96-5p was found to be significantly upregulated, whereas miR-146a-5p was significantly downregulated with the progression of disease to severe form. Interestingly, a strong positive correlation was found between the expression levels of miR-96-5p and miR-146a-5p and the platelet levels of the patients. Further, study of miR-146a-5p showed that it regulates the expression of the proteins which are involved in the immune responses. These results suggest that miR-96-5p and miR-146a-5p could be used as diagnostic and prognostic markers for dengue disease progression, in addition to the already available biochemical and pathological parameters. K E Y W O R D S dengue pathogenesis, dengue virus, exosomes, microRNA 1 | INTRODUCTION Dengue virus (DENV) is the causative agent of dengue fever, the most common mosquito-transmitted disease. It is a positive-sense cytoplasmic virus belonging to the Flavivirus genus of the family Flaviviridae. 1 There are four distinct serotypes of the dengue virus, namely DENV-1, DENV-2, DENV-3, and DENV-4, and the prevalence of each serotype differs depending on the geographical location. 2,3 Currently, no specific medical treatment is available for this disease, and no effective vaccine has been developed. The only licensed vaccine, Dengvaxia, has low efficacy against serotypes 1 and 2. 4Based on its severity, dengue infection has been categorized into different stages: dengue without warning (Plan A), dengue with warning (Plan B), and severe dengue fever (dengue hemorrhagic fever/dengue shock syndrome) (Plan C). 5 Dengue pathogenesis has been shown to be influenced mainly by the host immune response, leading to a cytokine storm, immune enhancement, secondary infection, and variation in viral serotype. 6 Not much progress has been made in identifying molecules that have a role in disease

Hepatitis C virus (HCV) infection is one of the most common causes of liver cancer. HCV infection causes chronic disease followed by cirrhosis, which often leads to hepatocellular carcinoma (HCC). In this study, we investigated the roles of exosome‐associated miRNAs in HCV‐induced disease pathology. Small RNA sequencing was performed to identify miRNAs that are differentially regulated in exosomes isolated from patient sera at two different stages of HCV infection: cirrhosis and hepatocellular carcinoma. Among the differentially expressed miRNAs, miR‐375 was found to be significantly upregulated in exosomes isolated from patients with cirrhosis and HCC. A similar upregulation was observed in intracellular and extracellular/exosomal levels of miR‐375 in HCV‐JFH1 infected Huh7.5 cells. The depletion of miR‐375 in infected cells inhibited HCV‐induced cell migration and proliferation, suggesting a supportive role for miR‐375 in HCV pathogenesis. miR‐375, secreted through exosomes derived from HCV‐infected cells, could also be transferred to naïve Huh7.5 cells, resulting in an increase in cell proliferation and migration in the recipient cells. Furthermore, we identified Insulin growth factor binding protein 4 (IGFBP4), a gene involved in cell growth and malignancy, as a novel target of miR‐375. Our results demonstrate the critical involvement of exosome‐associated miR‐375 in HCV‐induced disease progression.

The 2020 Nobel Prize in Physiology or Medicine was awarded jointly to Harvey J. Alter of the National Institute of Health (NTH), Michael Houghton of the University of Alberta and, Charles M. Rice of Rockefeller University. The Nobel Assembly at Karolinska Institute has awarded them the Nobel Prize for the discovery of Hepatitis C virus (HCV).