Hepatocyte growth factor (HGF) is reported to be down-regulated in pregnancy complications like intrauterine growth retardation and preeclampsia, which are associated with abnormal trophoblast migration/invasion. In this study, role of HGF and associated signaling pathways has been investigated in HTR-8/SVneo trophoblastic cells migration/invasion under normoxia (20% O 2) and hypoxia (2% O 2). HTR-8/SVneo cells exposed to hypoxia showed increase in migration and invasion as compared to cells incubated under normoxic conditions. The migration/invasion under both normoxic and hypoxic conditions was further enhanced after treatment with HGF. Subsequent to treatment with HGF, a significant increase in expression of MMP2 & MMP3 under normoxia and MMP1 & MMP9 under hypoxia was observed. Treatment of HTR-8/SVneo cells with HGF under hypoxia also led to decrease in TIMP1. Treatment of the cells with HGF led to activation of mitogen activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. Inhibition of MAPK by U0126 and PI3K by LY294002 led to concomitant decrease in the HGF-mediated migration/invasion of HTR-8/SVneo cells. HGF treatment under hypoxia also led to a significant increase in hypoxia inducible factor (HIF-1α) expression. Additionally, inhibition of HIF-1α by siRNA led to decrease in HGF-mediated migration of HTR-8/SVneo cells under hypoxic conditions. Inhibition of HGF activated MAPK and PI3K signaling led to reduction in HIF-1α expression under hypoxia. In conclusion, HGF facilitates HTR-8/SVneo cell migration/invasion by activation of MAPK/PI3K signaling pathways and increased expression of MMPs. HIF-1α has a role in HGF-mediated increase in migration under hypoxic conditions.

The review highlights the significance of mulberry fruits in both chemical and biological sagacity and their role as antioxidant, anticancer, antidiabetic, hepatoprotective, neuroprotective, anti-inflammatory, antiobesity, hypolipidemic, and antibacterial. Besides, having phytochemicals induced biological pathways and nutritional value. Although a number of mulberry fruits species available in nature, the review elucidates the specific role of Morus alba, Morus nigra, Morus rubra, whose functions in living systems are poorly implicit. Many Pharmacological properties of mulberry fruits which are discovered in the recent past for therapeutic purposes also highlighted. Further, ethnopharmacological relevance, medicinal aspects, and bioavailability of mulberry fruits are discussed in detail.

Inadequate migration and invasion of the trophoblast cells during embryo implantation is one of the reasons for pregnancy-related complications such as intrauterine growth restriction and preeclampsia. In the present study, relevance of WNT ligands and integrins associated with hepatocyte growth factor (HGF)-mediated migration of HTR-8/SVneo trophoblastic cells has been investigated. Treatment of HTR-8/SVneo cells with HGF led to a dose-dependent increase in their migration. RT-PCR studies revealed a significant increase in the transcripts of WNT4, WNT11, ITGA2, and ITGAV, which was further confirmed at protein level by Western blotting. HGF treatment also led to increased expression of integrin α2β1 and αVβ5 in HTR-8/SVneo cells. Silencing of WNT4, WNT11, ITGA2, and ITGAV by siRNA led to a significant decrease in HGF-mediated migration of cells. Treatment of cells with HGF led to activation of mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. Inhibition of MAPK/PKA, by selective inhibitors, led to decrease in the expression of above WNT ligands and integrins. Silencing of WNT4/WNT11 led to concomitant decrease in the expression of ITGA2 and ITGAV and vice versa. HGF treatment also led to significant increase in β-catenin expression, a downstream target of both WNT ligands and integrins. Silencing of β-catenin led to decrease in HGF-mediated migration. β-catenin expression was also down-regulated in WNT4/WNT11/ITGA2/ITGAV silenced cells suggesting a possible cross-communication of WNT ligands and integrins via β-catenin. These studies have established the significance of WNT4/WNT11 as well as ITGA2/ITGAV during HGF-mediated migration of HTR-8/SVneo trophoblastic cells.

Background:The development of colorectal carcinoma (CRC) involves many genetic and epigenetic alterations and methylation being an important epigenetic event has been described as a diagnostic and prognostic biomarker. Secreted Frizzled- Related Protein 1 (SFRP1) gene regulates diverse physiological processes via the Wnt signaling. Promoter hypermethylation of SFRP1 gene is an epigenetic regulation mechanism that downregulates SFRP1 protein level in the tumor, and happens to be one of the significant events in colorectal carcinogenesis. We studied the clinicopathological relationship of CRC including survival outcomes with SFRP1 gene promoter methylation.Methods:We evaluated promoter methylation status of SFRP1 gene by methylation-specific PCR (MS-PCR) in the tumor tissue in 54 cases of stage II-III CRC patients in north India. The MS-PCR result was further validated by bisulfite sequencing.Results:SFRP1 gene was methylated in 72.2% cases and un-methylated in 27.8%. We found, that SFRP1 gene methylation in tumor was associated with lymph node invasion (p=0.05). The mean overall survival was 22.318 months and 45.173 months respectively for patients with methylated and unmethylated SFRP1 gene (p= 0.010, log rank test), (HR = 17.313, 95% CI: 2.021-148.290 P=0.009).Conclusion:Study indicates that promoter methylation of SFRP1 gene is associated with lymph-node metastasis and poor mean overall survival and it can be a prognostic marker in CRC.

Severe Acute Respiratory Syndrome Corona Virus -2 (SARS-CoV-2), puzzled the whole world with its diverse, unique clinical spectrum, and unprecedented transmission dynamics. The disease caused by this virus is named as Coronavirus disease-19 (COVID-19), reported first time in Wuhan, China, in December 2019. It had spread to almost all countries of the world disrupting the health and economy of many countries. It was the recent zoonotic spillover disease reported in humans from the Coronavirus group, without proper medicine and non-existence of prior immunity, this disease posed a challenge to both the scientific and medical fraternity. The search for safe, effective drugs to treat the disease and vaccines against the causative agent SARS- CoV-2 had begun all over the world with public and private partnerships. Many countries are part of the solidarity trail for identifying the effective drugs, clinical trials and vaccines for this global pandemic. Here in this review, we are focussing on the different vaccine production platforms being used in the preparation of vaccines against SARS-CoV-2, their current status and prospects. Vaccine production technology significantly advanced in recent times by imbibing the cutting edge technologies such as nucleic acid based technologies such as DNA/RNA/Codon deoptimization and availability of safe and effective viral vectors produced through rDNA technology. The availability of complete genome sequence of SARS-CoV-2, geared up for the production of vaccine candidates based on these new vaccine production platforms, and in a record time of 4-5 months, these vaccine candidates entered in human clinical trials for the evaluation of safety and efficacy. Prior knowledge on SARS and MERS-CoV’s structural and genomic features, vaccine production platforms used in making vaccines against them greatly augmented in the SARS-CoV-2 vaccine efforts. As per World Health Organization (WHO) a total of202 vaccine candidates are under developing for SARS-CoV-2, among them 47 entered in clinical trials and 156 are in the preclinical stage. These vaccines are prepared by an amalgamation of both new and old traditional vaccine production platforms such as nucleic acid base platforms, inactivated, live attenuated, recombinant viral vectors, protein and peptide-based vaccines. The success of these vaccine candidates lies in the generation of effective immune response for SARS-CoV-2 across all age groups and people with co-morbidities. We briefly summarize the different strategies of SARS-CoV-2 vaccine production and their prospects with an emphasis on different routes of administration and added a basic mathematical model depicting the importance of vaccination for any pandemic.