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Background Naringenin is a powerful antioxidant and anti-inflammatory flavonoid which has been widely used as a therapeutic agent in various toxic models. However, few studies have clearly discussed the neuromodulatory effects of naringenin against different neurodegenerative disorders. Aim We investigated the neuroprotective efficacy of naringenin against 3-nitropropionic acid (3-NP)-induced neurobehavioral, biochemical and histopathological alterations in rats. Methods Albino Wistar rats were randomly divided into three experimental groups. Group 1, the vehicle administered group, received saline. Group 2 received 3-NP (20 mg/kg body weight, i.p.) for 4 consecutive days. Group 3 received naringenin (50 mg/kg body weight, p.o.) twice daily for a period of 4 days, 30 min before and 6 h after the 3-NP administration. On the 5th day, neurobehavioral experiments were performed to access the behavioral outcomes and the striatum tissue was used for analysis of the monoamine oxidase (MAO) activity and serotonin (5-HT) levels. In addition, astrocytes activation was observed by glial fibrillary acidic protein (GFAP) immunostaining. Results Our results showed that naringenin co-treatment provides neuroprotection against 3-NP-induced neurological disorders. Naringenin also increased the MAO activity and 5-HT levels in the striatum. Moreover, co-treatment with naringenin reduced the expression of GFAP protein in the striatal part and significantly attenuated the neuronal cell death. The findings of the present study suggest that naringenin provides neuroprotection and mitigates neurobehavioral alterations in experimental rats. Conclusion The results show that co-treatment with naringenin ameliorates 3-NP-induced HD-like symptoms in rats.

The coronavirus disease (COVID-19) is caused by a positive-stranded RNA virus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), belonging to the Coronaviridae family. This virus originated in Wuhan City, China, and became the cause of a multiwave pandemic that has killed 3.46 million people worldwide as of May 22, 2021. The havoc intensified with the emergence of SARS-CoV-2 variants (B.1.1.7; Alpha, B.1.351; Beta, P.1; Gamma, B.1.617; Delta, B.1.617.2; Delta-plus, B.1.525; Eta, and B.1.429; Epsilon etc.) due to mutations generated during replication. More variants may emerge to cause additional pandemic waves. The most promising approach for combating viruses and their emerging variants lies in prophylactic vaccines. Several vaccine candidates are being developed using various platforms, including nucleic acids, live attenuated virus, inactivated virus, viral vectors, and protein-based subunit vaccines. In this unprecedented time, 12 vaccines against SARS-CoV-2 have been phased in following WHO approval, 184 are in the preclinical stage, and 100 are in the clinical development process. Many of them are directed to elicit neutralizing antibodies against the viral spike protein (S) to inhibit viral entry through the ACE-2 receptor of host cells. Inactivated vaccines, to the contrary, provide a wide range of viral antigens for immune activation. Being an intracellular pathogen, the cytotoxic CD8+ T Cell (CTL) response remains crucial for all viruses, including SARS-CoV-2, and needs to be explored in detail. In this review, we try to describe and compare approved vaccines against SARS-CoV-2 that are currently being distributed either after phase III clinical trials or for emergency use. We discuss immune responses induced by various candidate vaccine formulations; their benefits, potential limitations, and effectiveness against variants; future challenges, such as antibody-dependent enhancement (ADE); and vaccine safety issues and their possible resolutions. Most of the current vaccines developed against SARS-CoV-2 are showing either promising or compromised efficacy against new variants. Multiple antigen-based vaccines (multivariant vaccines) should be developed on different platforms to tackle future variants. Alternatively, recombinant BCG, containing SARS-CoV-2 multiple antigens, as a live attenuated vaccine should be explored for long-term protection. Irrespective of their efficacy, all vaccines are efficient in providing protection from disease severity. We must insist on vaccine compliance for all age groups and work on vaccine hesitancy globally to achieve herd immunity and, eventually, to curb this pandemic.

PGE2 plays a critical role in angiogenesis, ischemic, and neuro-inflammatory disorders of the brain, which breakdown the blood-brain barrier (BBB). However, the effects of PGE2 on human brain endothelial cell (HBECs) migration, a key process in the angiogenic response and BBB stability, are not well defined. In this study, we investigated the mechanism of PGE2 in HBECs migration in vitro. Here we showed that PGE2 stimulated migration of HBECs in a dose-time and matrix-dependent manner, evaluated by the Boyden chamber assay, but other prostanoids failed to do so. PGE2 receptor (EP2; butaprost), EP3 (sulprostone), and EP4 (PGE1-OH) receptor agonists stimulated HBECs migration, but the silencing of EP significantly attenuated this effect. EP1 agonist (11-trinor PGE1) had no effect on HBECs migration on silencing of the EP1 receptor. We further showed that PGE2 stimulated cAMP production and activated protein kinase A (PKA), whereas pretreatment with the adenyl cyclase inhibitor (dideoxyadenosine; 1 μM) or PKA inhibitors, H89 (0.5 μM)/PKAI (1 μM), completely abrogated PGE2-induced migration. Furthermore, silencing of the EP2/EP4 receptors significantly inhibited PGE2-induced cAMP and PKA activation, whereas EP3 receptor silencing failed to do so. These results suggest that PGE2 regulates HBEC migration via cooperation of EP2, EP3, and EP4 receptors. Coupling of PGE2 to these receptors resulted in increased production of cAMP, which regulates HBEC migration via PKA pathway. The elucidation of molecular events involved is critical for the development of targeted strategies to treat cerebrovascular diseases associated with dysregulated angiogenesis.

Background COVID-19 pandemic has currently no vaccines. Thus, the only feasible solution for prevention relies on the detection of COVID-19-positive cases through quick and accurate testing. Since artificial intelligence (AI) offers the powerful mechanism to automatically extract the tissue features and characterise the disease, we therefore hypothesise that AI-based strategies can provide quick detection and classification, especially for radiological computed tomography (CT) lung scans. Methodology Six models, two traditional machine learning (ML)-based (k-NN and RF), two transfer learning (TL)-based (VGG19 and InceptionV3), and the last two were our custom-designed deep learning (DL) models (CNN and iCNN), were developed for classification between COVID pneumonia (CoP) and non-COVID pneumonia (NCoP). K10 cross-validation (90% training: 10% testing) protocol on an Italian cohort of 100 CoP and 30 NCoP patients was used for performance evaluation and bispectrum analysis for CT lung characterisation. Results Using K10 protocol, our results showed the accuracy in the order of DL > TL > ML, ranging the six accuracies for k-NN, RF, VGG19, IV3, CNN, iCNN as 74.58 ± 2.44%, 96.84 ± 2.6, 94.84 ± 2.85%, 99.53 ± 0.75%, 99.53 ± 1.05%, and 99.69 ± 0.66%, respectively. The corresponding AUCs were 0.74, 0.94, 0.96, 0.99, 0.99, and 0.99 (p-values

Introduction: The coronavirus pandemic has involved nearly all the countries of the world. The lockdowns and closure of educational institutes to reduce the risk of disease transmission has brought a change in the medium of teaching as most educational institutes have moved to the online mode. There is a widespread increase in stress as the number of cases and mortality associated with Coronavirus 2019 disease (COVID-19) continue each day. Aim: To assess the stress status of first year undergraduate medical students in reference to the coronavirus pandemic and the perception of first year undergraduate medical students in reference to the E-learning being carried out during the coronavirus pandemic. Materials and Methods: This was a cross-sectional web-based online survey that was conducted using a questionnaire in August 2020 at Hamdard Institute of Medical Sciences and Research, New Delhi, India. The questionnaire was prepared and reviewed by the involved faculty members of the project and it was approved by a faculty from Department of Psychiatry. Reliability of questionnaire was measured using Cronbach’s alpha (0.89). A questionnaire with 20 questions was administered via Google forms to all 100 students of first year MBBS course. Some of the questions in the questionnaire were framed to assess the stress status of the students; some were designed to study students’ perception of E-learning. Data was represented as the percentage distribution of response for each question. Results: Ninety five responses were received, after accounting for exclusion factors; data was compiled for 91 respondents. Out of the 91 participants in the study, 48.4% were males (n=44) and 51.6% were females (n=47). Most of the students in this study (84.6%) felt that online teaching had helped in learning Physiology theory; around 43% students found online practical teaching useful. Around 39% students have reported internet connectivity issues all the time while 59% faced problem sometimes. Total 51.6% of students had difficulty in accessibility to devices. Due to coronavirus pandemic, 37.4% of students have reported to be under stress. Around 33% reported feeling unsafe all the time while 39.5% felt unsafe some of the times. Conclusion: Students found online teaching more helpful in learning Physiology theory than practical. Majority of class reported internet connectivity issues. All the responders agreed that this pandemic affected their regular life. Most of the students felt that online classes have helped them to remain positive and motivated towards study.

Sterile inflammation (SI) is an essential process in response to snakebite and injury. The venom induced pathophysiological response to sterile inflammation results into many harmful and deleterious effects that ultimately leads to death. The available treatment for snakebite is antiserum which does not provide enough protection against venom-induced pathophysiological changes like haemorrhage, necrosis, nephrotoxicity and often develop hypersensitive reactions. In order to overcome these hindrances, scientists around the globe are searching for an alternative therapy to provide better treatment to the snake envenomation patients. In the present study TiO2 (Titanium dioxide)-NPs (Nanoparticles) has been assessed for antisnake venom activity and its potential to be used as an antidote. In this study, the synthesis of TiO2-NPs arrays has been demonstrated on p-type Silicon Si substrate (∼30 ohm-cm) and the surface topography has been detected by Field-emission scanning electron microscopy (FESEM). The TiO2-NPs successfully neutralized the Daboia russelii venom (DRV) and Naja kaouthia venom (NKV)-induced lethal activity. Viper venom induced haemorrhagic, coagulant and anticoagulant activities were effectively neutralized both in in-vitro and in vivo studies. The cobra and viper venoms-induced sterile inflammatory molecules (IL-6, HMGB1, HSP70, HSP90, S100B and vWF) were effectively neutralised by the TiO2-NPs in experimental animals.

Piperidine is an important pharmacophore, a privileged scaffold and an excellent heterocyclic system in the field of drug discovery which provides numerous opportunities in studying/exploring this moiety as an anticancer agent by acting on various receptors of utmost importance. Cancer is an uncontrolled division of cells that results in the formation of tumour which have the potential to migrate to other parts of the body (metastasis) finally becoming a major threat to human population. Since piperidine displayed great potential in this area it is being further probed to get novel entities for the treatment of cancer. This review throws light on recent biological expansions of piperidine along with structure activity relationships to deliver association between various synthesized newer/novel derivatives and receptor sites.

Myocardial infarction (MI), atherosclerosis and other inflammatory and ischemic cardiovascular diseases (CVDs) have a very high mortality rate and limited therapeutic options. Although the diagnosis is based on markers such as cardiac Troponin-T (cTrop-T), the mechanism of cTrop-T upregulation and release is relatively obscure. In the present study, we have investigated the mechanism of cTrop-T release during acute hypoxia (AH) in a mice model by ELISA & immunohistochemistry. Our study showed that AH exposure significantly induces the expression and release of sterile inflammatory as well as MI markers in a time-dependent manner. We further demonstrated that activation of TLR3 (mediated by eRNA) by AH exposure in mice induced cTrop-T release and Poly I:C (TLR3 agonist) also induced cTrop-T release, but the pre-treatment of TLR3 immuno-neutralizing antibody or silencing ofTlr3gene or RNaseA treatment two hrs before AH exposure, significantly abrogated AH-induced Caspase 3 activity as well as cTrop-T release. Our immunohistochemistry and Masson Trichrome (MT) staining studies further established the progression of myocardial injury by collagen accumulation, endothelial cell and leukocyte activation and adhesion in myocardial tissue which was abrogated significantly by pre-treatment of RNaseA 2 hrs before AH exposure. These data indicate that AH induced cTrop-T release is mediated via the eRNA-TLR3-Caspase 3 pathway.

High mobility group box 1 protein (HMGB1), a sterile inflammatory molecule and damage-associated molecular pattern (DAMP) released from various cells during stress has been implicated in inflammation. Several reports show that there is a direct relationship between inflammation and cardiovascular diseases (CVDs) such as thrombosis, hypertension, insulin resistance, preeclampsia, etc. Here, we intend to summarize the concept of the emerging link between HMGB1 and CVDs. Furthermore, we will discuss the possible therapeutic strategies that target HMGB1 for the treatment of different CVDs.

We herein report the design, synthesis and molecular docking studies of 2,4-thiazolidinedione derivatives containing benzene sulphonyl group which are docked against the Peroxisome Proliferator Activated Receptor (PPARγ) target. Compound 7p was most effective in lowering the blood glucose level as compared to standard drugs pioglitazone and rosiglitazone. Compound 7p exhibited potent PPAR-γ transactivation of 61.2% with 1.9 folds increase in gene expression. In molecular docking studies 7p showed excellent interactions with amino acids TYR 473, SER 289, HIE 449, TYR 327, ARG 288, MET 329 and LEU 228. Compound 7p did not cause any damage to the liver without any noteworthy weight gain and may be considered as promising candidates for the development of new antidiabetic agents.