Recovery of Human Embryonic Stem Cells-Derived Neural Progenitors Exposed to Hypoxic-Ischemic-Reperfusion Injury by Indirect Exposure to Wharton's Jelly Mesenchymal Stem Cells Through Phosphatidyl-inositol-3-Kinase Pathway.

Increasing evidence suggests that mesenchymal stem cells(MSCs) have beneficial effects in hypoxic ischemic reperfusion injury, but the underlying mechanisms are unclear. Here, we first examined the effect of OGD reperfusion injury on the vulnerability of human NPs derived from human embryonic stem cells (hESCs) with regard to cell survival and oxidative stress. Cellular deregulation was assessed by measuring glutathione levels, basal calcium and intracellular calcium [Ca2+]i response under KCl stimulation, as well as the key parameters of proliferation, glial progenitor marker expression and migration. Next, the influence of WJ-MSCs in recovering these parameters was evaluated, and the role of Phosphatidyl-inositol-3-Kinase(PI3K) pathway in actuating the protective effect was assessed. OGD reperfusion injury induced significant increases in cell death, ROS generation, oxidative stress susceptibility and decreased glutathione levels in NPs, accompanied by rises in basal [Ca2+]i, KCl-induced [Ca2+]i, expression of K+ leak channel(TASK1), and declines in proliferation, migration potential and glial progenitor population. The introduction of WJ-MSCs(after 2 h of reperfusion) through a non-contact method brought about significant improvement in all these cellular parameters as observed after 24hrs, and the PI3K pathway played an important role in the neuroprotection process. Presence of WJ-MSCs increased the expression of survival signals like phosphorylated Akt/Akt and PI3K in the OGD-reperfused NPs. Our data clearly demonstrate for the first time that soluble factors from WJ-MSCs can not only ameliorate survival, proliferation, migration and glial progenitor expression of OGD-reperfused NPs, but also regulate their intracellular Ca2+ response to KCl stimulation and expression of TASK1 through the PI3K pathway.

Twitter Mediated Sociopolitical Communication During the COVID-19 Pandemic Crisis in India.

While Twitter has grown popular among political leaders as a means of computer-mediated mass media communication alternative, the COVID-19 pandemic required new strategies for socio-political communication to handle such a crisis. Using the case of India, which was one of the worst-hit countries and is also the world's largest democracy, this research explicates how political leaders responded to the COVID-19 crisis on Twitter during the first wave as it was the first time such a crisis occurred. Theoretical frameworks of discursive leadership and situational crisis communication theory have been used to analyze interactions based on the usage patterns, the content of communication, the extent of usage in relation to the severity of the crisis, and the possible role of leaders' position along with the status of their political party. The sample consisted of tweets posted by six prominent political leaders in India across the four consecutive lockdown periods from 25th March to 31st May 2020. A total of 4,158 tweets were scrapped and after filtering for retweets, the final dataset consisted of 2,809 original tweets. Exploratory data analysis, sentiment analysis, and content analysis were conducted. It was found that the tweets had an overall positive sentiment, an important crisis management strategy. Four main themes emerged: crisis management information, strengthening followers' resilience and trust, reputation management, and leaders' proactiveness. By focusing on such discursive aspects of crisis management, the study comprehensively highlights how political interactions on twitter integrated with politics and governance to handle COVID-19 in India. The study has implications for the fields of digital media interaction, political communication, public relations, and crisis leadership.

Evaluating In Vitro Neonatal Hypoxic-Ischemic Injury Using Neural Progenitors Derived from Human Embryonic Stem Cells.

In hypoxic-ischemic encephalopathy, the neural progenitors (NPs) of the developing brain fail to replenish the oligodendrocyte progenitor cells lost during hypoxic-ischemic injury (HII). In this study, we aim to examine the influence of HII on the vulnerability of human NPs derived from human embryonic stem cells with regard to cell survival and oxidative stress, followed by assessment of cellular deregulation through measuring glutathione levels, basal calcium, glutamate release, and intracellular calcium ([Ca2+]i) response under KCl and ATP stimulation. NPs were further evaluated for their fundamental potential of self-renewal and proliferation, neural and glial progenitor pool, and migration. Oxygen-glucose deprivation (OGD) of 90 min was sublethal for NPs, yet significantly increased reactive oxygen species generation and oxidative stress susceptibility, and decreased glutathione levels, along with a rise in glutamate release, basal [Ca2+]i, and KCl and ATP-induced [Ca2+]i. Distinct increase in gene expression for K+ leak channel (Twik-related acid-sensitive K+ channel 1 [TASK-1]) and purinergic receptor P2X7, and decrease of voltage-gated Kv channels Kv1.5, Kv4.2, and Kv4.3 were observed. TASK-1 increase was detected by FACS too. OGD-insulted NPs showed reduced migration potential and decline in glial progenitor population. This study thus demonstrates for the first time that brief exposure of OGD does not reduce the NP population, its proliferation, and self-renewal, but can induce significant alteration in oxidative stress susceptibility, glutamate release, [Ca2+]i response to physiological stimulus, migration, and glial progenitor pool. We thus infer that treatment strategies need to target repair of NPs of the developing brain that is affected during intrapartum asphyxia, leading to varying neurologic complications such as seizure, mental retardation, and/or cerebral palsy.

Immune-mediated neurological manifestations of dengue virus- a study of clinico-investigational variability, predictors of neuraxial involvement, and outcome with the role of immunomodulation.

INTRODUCTION: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic. MATERIALS AND METHODS: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Laboratory as well as clinicoradiological data, the predictors of outcome, and the role of immunomodulation in determining the final result were analyzed. RESULTS: Out of the 1627 confirmed dengue cases, 14.6% developed neurological complications and only 4.86% cases had IMNC. Among the IMNC seen, the majority of the patients had the onset of their manifestations in the subacute (7-30 days) latency period; however, there was no mortality seen. We found Miller Fisher syndrome (MFS), limbic encephalitis, and immune-mediated cerebellar demyelination (IMCD) as the new findings in the IMNC spectrum. Patients with DF were more prone to developing brachial plexus neuritis and polyneuritis cranialis, whereas those patients with a severe syndrome were more commonly associated with Guillain-Barre syndrome (GBS). Significant (P < 0.001) predictors of central nervous system involvement were anemia, an elevated hematocrit, and the presence of DSS, whereas patients with a higher mean body temperature, DF, and elevated hematocrit were more prone to developing peripheral nervous system manifestations. The platelets counts and the hemoglobin levels had a negative correlation whereas the hematocrit value, the mean body temperature, and the alanine aminotransferase levels had a moderately significant positive correlation for the development of IMNC. The immunomodulatory therapy (IMT), if initiated after fever abatement led to a significant clinically favorable outcome at 3 months, especially in patients with GBS, polyneuritis cranialis, and brachial plexus neuritis. CONCLUSION: The spectrum of IMNC is vast and may include MFS, limbic encephalitis and IMCD. Early initiation of IMT, in the presence of significant predictors, may reduce the IMNC-related morbidity.

Formation and Characterization of Protein Corona Around Nanoparticles: A Review.

Recent years have witnessed unprecedented increase in the use of nanoparticles in various sectors viz. electronics, catalysis, agriculture, textile, cosmetics, bio-medicine, packaging, house-holds and food-associated consumer products. This has led to the inevitable release of nanoparticles into the environment, which can have negative impact on living beings. Humans can also be exposed to these nanoparticles either intentionally or accidently. Nanoparticles can enter in the human body through food chain, inhalation, open wounds, drugs and intravenous injections etc. In majority of these cases, the nanoparticles may pass through the various cell layers, cell sap and finally enter into the blood. Upon interaction with biological fluid, nanoparticles come in close proximity particularly to the proteins present in the fluid. The assembly of proteins surrounding the nanoparticle's surface is called as protein corona and their complex is known as protein-nanoparticle complex. Formation of protein corona is a vibrant and driving process, which plays a pivotal role in the functioning of nanoparticles in biological systems. Moreover, due to interaction of proteins with nanoparticles, conformational changes may occur in the native structure of protein, which may lead to change in the functioning of proteins towards its cellular interaction. The present review provides in-depth knowledge about the formation of protein corona around nanoparticles and the factors regulating this process. Further, it discusses various techniques that can be used for the protein corona analysis and obtaining information about molecular consequences upon nanoparticle's exposure. Finally, the functional aspects of protein-nanoparticle complex have been discussed in detail. In-depth understanding of protein-nanoparticles complex can be instrumental to generate well-suited nanoparticles with desired surface characteristics in the way to biological application.

Evaluation of DNA damage and metabolic syndrome parameters in diabetic rabbits supplemented with antioxidants.

The aim of the present study is to evaluate the extent of DNA damage in diabetes and metabolic syndrome and to assess the variations after supplementation with antioxidants. We used comet assay to measure DNA damage in freshly isolated lymphocytes from a total of 12 rabbits, distributed into four experimental groups (n = 3 rabbits per group): non-diabetic (control, G1), diabetic (G2), diabetic supplemented with vitamin C (G3), and diabetic supplemented with vitamin E (G4). Also their serum was isolated for estimation of parameters that contribute to metabolic syndrome. Malondialdehyde (MDA), the marker of oxidative stress was also assessed. Mean values of DNA damage (tail length, expressed as mum), lipid peroxidation and concentration of blood glucose, MDA, C-reactive protein, and triglycerides were higher in G2; whereas the mean values of concentration of high-density lipoprotein, serum paraoxonase-1 activity and small dense low-density lipoprotein oxidation time were reduced in G2 followed by G3, G4, and G1. A significant positive correlation was observed between the DNA damage and elevated parameters of metabolic syndrome (r = 0.66, 0.96, 0.89, 0.75, 0.88, 0.92, 0.99, P < 0.05) and a significant negative correlation (r = -0.91, -0.75, -0.98, P < 0.05) was found between the DNA damage and declined parameters of metabolic syndrome. These data indicate that the extent of DNA damage is more in diabetic rabbits as compared to the non-diabetic or antioxidant supplemented group. Abnormal metabolic parameters and their correlation with DNA damage, suggest the risk of development of metabolic syndrome in diabetic group but a possibility of repression by antioxidants because of their ability to counteract oxidative stress.