Endothelial dysfunction is related to the reduced bioavailability of nitric oxide (NO) and plays a significant role in developing hypertension. The intake of a diet rich in antioxidants decreases the ...threat of hypertension. Cissus quadrangularis possesses antioxidant, anti-inflammatory, and hypocholesterolemic activities. However, to date, no studies have been performed to explore this plant's antihypertensive and vasorelaxant activity. Herein, we investigated the chronic effect of C. quadrangularis on blood pressure as well as vascular function in hypertensive rats.
Male spontaneously hypertensive rats (SHR) were randomly divided into two groups. Normotensive Wistar rats were taken as the control group. The treatment was done using ethanolic extract of C. quadrangularis (EECQ) at a dose of 200 mg/kg.
The administration of EECQ for six weeks reduced the systolic blood pressure, mean arterial blood pressure, and heart rate. It also alleviated the cardiac and renal hypertrophy indices. Supplementation of EECQ improved the endothelium-dependent aortic vasodilation induced by acetylcholine. It restored the NO level and endothelial NO synthase expression in the aorta. Subsequently, the extract alleviates the oxidative stress and inflammatory markers in SHR rats.
Thus, in the present study, the chronic treatment of EECQ to genetically hypertensive rats improved endothelium-dependent relaxation in addition to its antihypertensive effect by eNOS activation and inhibition of ROS production, inflammation.
Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising
Msi1
and
Msi2
is known to control RNA ...stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore,
Msi2
was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified
Msi2
isoforms 1, 4, and 5, and two novel putative isoforms labeled as
Msi2
6 and 7 to be expressed in the heart. Overexpression of
Msi2
isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally,
Msi2
exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of
Msi2
isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for
Msi2
. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified
Cluh
and
Smyd1
as direct downstream targets of
Msi2
. Overexpression of
Cluh
and
Smyd1
inhibited
Msi2
-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that
Msi2
induces hypertrophy, mitochondrial dysfunction, and heart failure.
Increased proliferation, inflammation, and endothelial microparticle (EMP) generation in the pulmonary vasculature lead to endothelial dysfunction in pulmonary hypertension (PH). Interestingly, MK2, ...a downstream of p38MAPK, is a central regulator of inflammation, proliferation, and EMP generation in cardiovascular diseases. However, the role of MK2 in pulmonary endothelial dysfunction remains unexplored.
The Human Pulmonary Artery Endothelial cells (HPAECs) were exposed to hypoxia (1% O2) for 72 h, and MK2 inhibition was achieved by siRNA treatment. Western blotting, qualitative RT-PCR, immunocytochemistry, flow cytometry and enzyme-linked immunoassays were conducted to study pathological alterations and molecular mechanisms. Neoangiogenesis was studied using cell migration and tubule formation assays. For in vivo study, Male Sprague Dawley rats and MK2 knock-out mice with littermate control were treated with monocrotaline (MCT) 60 mg/kg and 600 mg/kg, respectively (s.c. once in rat and weekly in mice) to induce PH. MMI-0100 (40 μg/kg, i.p. daily for 35 days), was administered in rats to inhibit MK2.
MK2 inhibition significantly decreased inflammation, cell proliferation, apoptosis resistance, and improved mitochondrial functions in hypoxic HPAECs. Hypoxia promoted cell migration, VEGF expression, and angiogenesis in HPAECs, which were also reversed by MK2 siRNA. MK2 inhibition decreased EMP generation and increased the expression of p-eNOS in hypoxic HPAECs, a marker of endothelial function. Furthermore, MK2 deficiency and inhibition both reduced the EMP generation in mice and rats, respectively.
These findings proved that MK2 is involved in endothelial dysfunction, and its inhibition may be beneficial for endothelial function in PH.
The designated COVID-19 testing laboratories of Virus Research Diagnostic Laboratory network (All India Institute of Medical Sciences, New Delhi; Sawai Man Singh Medical College, Jaipur; and King ...George's Medical University, Lucknow) referred the specimens (throat swab/nasal swab, oropharyngeal swab/sputum) to the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, after screening for envelope (E) gene by real-time RT-PCR was done6. From each well of cell culture plate, on the third post-infection day (PID-3) of passage-1 (P-1), 50 μl of supernatant was taken and tested for SARS-CoV-2 using real-time RT-PCR for E and RNA-dependent RNA polymerase (RdRp) (2) genes as described earlier7,8. Virus replication was confirmed using real-time RT-PCR with RNA extracted from the cell culture medium on PID-3. The number of virus copies in the isolates at P-1 in Vero CCL-81 cells ranged from 5.18×107 to 8.12×108 copy/ml and increased 1-26 fold to a range of 1.69×108 to 6.77×109 in the cell culture supernatants at P-2 Table 1.
Sir, The single-stranded RNA genome of the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) about 29.9 kb in length and encoding about 9860 amino acids, was annotated to ...possess 14 open reading frames (ORFs) and 27 proteins1,2. Throat swab/nasal swab specimens collected from the 1,920 individuals in Iran were tested at the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV) Pune, using real-time reverse transcription-polymerase chain reaction (RT-PCR) protocols to detect RdRp (1), RdRp (2), E and N genes as described elsewhere8. A recent study has identified the earliest Italian importation of SARS-CoV-2 to a case from Shanghai, China, and has also identified at least two circulating variants in Italy12. ...it is likely that the former strain (Italian cohort) has its origin from China, whereas the latter strain (contacts in Agra, n=2) appears to have been from a European cluster involving an entry into Germany that preceded the first cases in Italy by almost a month12,13. Acknowledgment: Authors thank Prof. (Dr) Balram Bhargava, Director-General, Indian Council of Medical Research (ICMR) & Secretary, Department of Health Research (DHR), Ministry of Health & Family Welfare (MoHFW), New Delhi for the support.
Zika virus (ZIKV) infection in human has been reported from Gujarat and Tamil Nadu states during the year 2016 and 2017 respectively. In paucity of complete genome data of ZIKV, the analysis and ...prediction were not possible. Zika cases were reported in Jaipur city, Rajasthan, India during the period of 21st September 2018 to 29th October 2018. In order to understand the circulating ZIKV strain in Rajasthan state about ten human serum samples from the positive cases of Jaipur city, Rajasthan state considering the locality and clustering variations were sequenced using next-generation sequencing (NGS) platform. Complete genome phylogenetic analysis of Jaipur city sequences with known GenBank ZIKV sequences revealed that the outbreak in Jaipur city was being caused by ZIKV belonging to Asian lineage. Partial genome sequencing revealed the presence of a pre-outbreak strain of ZIKV in Gujarat and current outbreak strain of Asian lineage in Tamil Nadu. Further sequence analysis of the five ZIKV positive samples of Jaipur revealed that the S139N and A188V mutations, linked to enhanced neurovirulence and transmission in animal models, were not found in the current outbreak strain. Whether this strain can cause birth defects and cause large outbreaks is not currently known, but they should be treated as such until more is known. With the identification of ZIKV in Gujarat, Tamil Nadu, and recent outbreaks of ZIKV in Rajasthan and Madhya Pradesh states alarm for India to enhance surveillance in other states and monitor the mutation and evolutionary changes in circulating Zika strains.
•Lack of complete Zika virus (ZIKV) sequence from India hampers circulating strain identification.•During the year 2018, Zika cases (n = 159) were reported in Jaipur, Rajasthan state, India.•Ten selected ZIKV positive serum samples from Jaipur city were sequenced to determine its lineage.•Complete genome analysis reveals that ZIKV Jaipur sequences (n = 5) belong to Asian lineage.•Partial genome analysis determined Gujarat as pre- and Rajasthan as current Asian outbreak strain.
•This study led to the detection of the Crimean Congo hemorrhagic fever virus (CCHFV) in humans, livestocks, and ticks.•Four human samples and thirteen Hyalomma tick pools were found to be CCHFV RNA ...positive.•Two different types of glycoprotein precursor (M) segments were observed in the tick samples.•This study proposes the circulation of multiple CCCHFV lineages in Rajasthan.
Crimean Congo hemorrhagic fever (CCHF) is a zoonotic viral disease presenting with fever and hemorrhagic manifestations in humans. After several outbreaks of CCHF being reported from Gujarat since 2011 till 2019 and from Rajasthan in 2014 and 2015, the present study reports the CCHF outbreak which was recorded from five human cases in three districts Jodhpur, Jaisalmer, and Sirohi of Rajasthan state since August 2019 till November 2019. A high percent of positivity was recorded in livestock animal samples for the CCHFV IgG antibody. CCHF virus (CCHFV) positive human blood samples and Hyalomma tick pool samples were sequenced using next-generation sequencing method. Two different M segment genotypes, encoding glycoprotein precursor, were identified from tick pools in the study: first from Asian and second from African lineage. The L gene (polymerase) and the S gene (nucleocapsid) clustered in the Asian lineage. The present study illustrates the existence of two different CCHFV lineages being circulating within the Hyalomma tick pools in the Rajasthan state, India. We also observed 3.56% amino acid changes between the death and the survived case of CCHFV in the M gene. This report also sets an alarm to enhance human, tick and livestock surveillance in other districts of Rajasthan and nearby states of India. Biosafety measures, barrier nursing along with the availability of personal protective equipment and ribavirin drug will always be a mainstay in preventing nosocomial infection for proper case management.
PDF
