Explore the vast range of titles available.

Purpose. Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. Methods. This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. Results. There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). Conclusion. IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Valproic acid (VPA) induced rodent model of autism is a widely accepted and extensively used rodent model to investigate the pharmacotherapy against autism. But, to date, its validation, suitability, and applicability as a well defining autistic model are still questionable. Previous research efforts highlighted that this model shows various core defining features of autism and related pathways, hence it is very necessary to explore its authenticity as a well-suited model for autism. Therefore, in this review, we summarize the preclinical and neurobiological relevant validated features, involved etiological mechanism, biological markers, treatment responses, drawbacks, current approaches, and future perspectives of VPA-induced model of autism. This review would help in deciphering the validation of the VPA-induced autistic model and its suitability as an experimental model of autism. A thorough investigation of behavioral, molecular, and neurobiological processes in animal models of autism would help in investigating the exact causation and effective treatment for autism.

Embryonic valproic acid (VPA) has been considered a potential risk factor for autism. Majority of studies indicated that targeting autism-associated alterations in VPA-induced autistic model could be promising in defining and designing therapeutics for autism. Numerous investigations in this field investigated the role of canonical Wnt signaling cascade in regulating the pathophysiology of autism. The impaired blood-brain barrier (BBB) permeability and mitochondrial dysfunction are some key implied features of the autistic brain. So, the current study was conducted to target canonical Wnt signaling pathway with a natural polyphenolic modulator cum antioxidant namely fisetin. A single dose of intraperitoneal VPA sodium salt (400 mg/kg) at gestational day 12.5 induced developmental delays, social behaviour impairments (tube dominance test), and anxiety-like behaviour (sucrose preference test) similar to autism. VPA induced mitochondrial damage and over-activated the canonical Wnt signaling which further increased the blood-brain barrier (BBB) disruption, apoptosis, and neuronal damage. Our findings revealed that oral administration of 10 mg/kg gestational fisetin (GD 13-till parturition) improved social and anxiety-like behaviour by modulating the ROS-regulated mitochondrial-canonical Wnt signaling. Moreover, fisetin controls BBB permeability, apoptosis, and neuronal damage in autism model proving its neuroprotective efficacy. Collectively, our findings revealed that fisetin-evoked modulation of the Wnt signaling cascade successfully relieved the associated symptoms of autism along with developmental delays in the model and indicates its potential as a bioceutical against autism. Graphical Abstract

RationaleStressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings.ObjectivesThis study was aimed to investigate the effect of orally administered Nigella sativa (0.2 mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats.MethodsIn the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out.ResultsPresent investigation indicated that acute stress of 1.5 h daily for 20 days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment.ConclusionsIt is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry.

Tannic acid (TA) is a metal chelating polyphenol that plays a crucial role in metal detoxification, but its modulatory role in co-exposure of these heavy metals’ exposure needs to be explored. Cadmium (Cd) and nickel (Ni) are inorganic hazardous chemicals in the environment. Humans are prone to be exposed to the co-exposure of Cd and Ni, but the toxicological interactions of these metals are poorly defined. Present study was undertaken to study the preventive role of TA in Cd–Ni co-exposure-evoked hepato-renal toxicity in BALB/c mice. In the current investigation, increased oxidative stress in metal intoxicated groups was confirmed by elevated peroxidation of the lipids and significant lowering of endogenous antioxidant enzymes. Altered hepato-renal serum markers, DNA fragmentation, and histological alterations were also detected in the metal-treated groups. Present study revealed that Cd is a stronger toxicant than Ni and when co-exposure was administered, additive, sub-additive, and detrimental effects were observed. Prophylactic treatment with TA significantly reinstated the levels of lipid peroxidation (LPO), non-enzymatic, and enzymatic antioxidants. Moreover, it also restored the serum biomarker levels, DNA damage, and histoarchitecture of the given tissues. TA due to its metal chelating and anti-oxidative properties exhibited cyto- and genoprotective potential against Cd–Ni co-exposure-induced hepatic and renal injury.

Autism is a neurodevelopmental condition, and it's associated pathophysiology, viz., oxidative stress and altered cellular homeostasis, has been extensively intertwined with behavioral impairments. Therefore, targeting oxidative stress and redox cellular homeostasis could be beneficial in relieving autistic-like symptoms. For this purpose, we examined a library of nutraceutical compounds that led us to a bioflavonoid fisetin. Autism-like neurobehavior was induced by subjecting the pregnant rodents to valproic acid at the time of neural tube closure (GD12.5). In this novel study, fisetin was evaluated for its neuroprotective potential at gestational (GD13 until delivery) and post-weaning developmental windows (PND 23–32) in VPA-induced rodent model of autism. Developmental VPA exposure increased intracellular ROS production, oxidative stress, altered AChE and ATPases in brain regions, and induced autistic-like behavioral impairments (social, repetitive, stereotyped, and sensorimotor). The present findings suggested that gestational and post-weaning fisetin treatment significantly improved the behavioral impairments by attenuating elevated oxidative stress, ROS, lipid peroxidation, and re-establishing redox homeostasis. Also, it effectively reinstated the reduced levels of endogenous antioxidants, glutathione, AChE, and ATPases by its antioxidant potential. Therefore, fisetin with its properties could be used as a potential therapeutic agent in overcoming the symptoms associated with autism.

During the COVID-19 pandemic, governments in many countries worldwide, including India, imposed several restriction measures, including lockdowns, to prevent the spread of the infection. COVID-19 lockdowns led to a reduction in gaseous and particulate pollutants in ambient air. In the present study, we investigated the substantial changes in selected volatile organic compounds (VOCs) after the outbreak of the coronavirus pandemic and associations with health risk assessments in industrial areas. VOC data from 1 January 2019 to 31 December 2021 were collected from the Central Pollution Control Board (CPCB) website, to identify percentage changes in VOC levels before, during, and after COVID-19. The mean TVOC levels at all monitoring stations were 47.22 ± 30.15, 37.19 ± 37.19, and 32.81 ± 32.81 µg/m3 for 2019, 2020, and 2021, respectively. As a result, the TVOC levels gradually declined in consecutive years due to the pandemic in India. The mean TVOC levels at all monitoring stations declined from 9 to 61% during the pandemic period as compared with the pre-pandemic period. In the current study, the T/B ratio values ranged from 2.16 (PG) to 26.38 (NL), which indicated that the major pollutant contributors were traffic and non-traffic sources during the pre-pandemic period. The present findings indicated that TVOC levels had positive but low correlations with SR, BP, RF, and WD, with correlation coefficients (r) of 0.034, 0.118, 0.012, and 0.007, respectively, whereas negative correlations were observed with AT and WS, with correlation coefficients (r) of −0.168 and −0.150, respectively. The lifetime cancer risk (LCR) value for benzene was reported to be higher in children, followed by females and males, for the pre-pandemic, pandemic, and post-pandemic periods. A nationwide scale-up of this study’s findings might be useful in formulating future air pollution reduction policies associated with a reduction in health risk factors. Furthermore, the present study provides baseline data for future studies on the impacts of anthropogenic activities on the air quality of a region.