Quality of Life and Its Biopsychosocial Determinants: A Study Among the Yadav Community From Delhi, India.

Introduction The COVID-19 pandemic has not only affected the physical and mental health of people but has also had a detrimental impact on their quality of life (QoL). Therefore, ways to improve the QoL must be promoted for the overall well-being of individuals and society. The present study aims to assess the status of QoL and understand its association with physical and mental variables among the Yadav community of Delhi. Methods A cross-sectional study was conducted among 600 participants aged 18 to 55 years. Participants were recruited based on inclusion criteria, that is, individuals aged between 18 and 55 years, residing in Delhi, belonging to the Yadav community, and exclusion criteria, that is, pregnant females, lactating mothers, and individuals with any chronic illness or suffering from COVID-19. Data were analyzed in IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York) using various descriptive and inferential statistics. Results Mental disorders were found to have a negative impact on QoL. The participants detected with higher levels of stress and depression reported a significant decrease in their scores (p ≤ 0.001) across all the domains of QoL. Hypertensive individuals have significantly lower mean scores than normal individuals across all domains. The regression analysis revealed that all these predictors have a negative impact on QoL. The present study indicated that women have a lower QoL than men. Among the four domains of QoL, the participants in the social domain had the highest proportion of good QoL, followed by the environmental domain. Conclusion This study reveals that the predictors of physical and mental health adversities have a negative association with QoL, and the results were significant across all the domains. It affects an individual's overall well-being, leading to decreased productivity, work-life balance, and happiness. The status of QoL among the participants was poor in the psychological domain and good in the social domain. Intervention programs based on diverse sociocultural practices should be targeted toward improving QoL by understanding the health needs and risks of different communities in Delhi.

Unveiling the epigenetic landscape of plants using flow cytometry approach.

Plants are sessile creatures that have to adapt constantly changing environmental circumstances. Plants are subjected to a range of abiotic stressors as a result of unpredictable climate change. Understanding how stress-responsive genes are regulated can help us better understand how plants can adapt to changing environmental conditions. Epigenetic markers that dynamically change in response to stimuli, such as DNA methylation and histone modifications are known to regulate gene expression. Individual cells or particles' physical and/or chemical properties can be measured using the method known as flow cytometry. It may therefore be used to evaluate changes in DNA methylation, histone modifications, and other epigenetic markers, making it a potent tool for researching epigenetics in plants. We explore the use of flow cytometry as a technique for examining epigenetic traits in this thorough discussion. The separation of cell nuclei and their subsequent labeling with fluorescent antibodies, offering information on the epigenetic mechanisms in plants when utilizing flow cytometry. We also go through the use of high-throughput data analysis methods to unravel the complex epigenetic processes occurring inside plant systems.

Flow cytometry: Aspects and application in plant and biological science.

Flow cytometry is a potent method that enables the quick and concurrent investigation of several characteristics of single cells in solution. Photodiodes or photomultiplier tubes are employed to detect the dispersed and fluorescent light signals that are produced by the laser beam as it passes through the cells. Photodetectors transform the light signals produced by the laser into electrical impulses. A computer then analyses these electrical impulses to identify and measure the various cell populations depending on their fluorescence or light scattering characteristics. Based on their fluorescence or light scattering properties, cell populations can be examined and/or isolated. This review covers the basic principle, components, working and specific biological applications of flow cytometry, including studies on plant, cell and molecular biology and methods employed for data processing and interpretation as well as the potential future relevance of this methodology in light of retrospective analysis and recent advancements in flow cytometry.

A recent update on development, synthesis methods, properties and application of natural products derived carbon dots.

Natural resources are practically infinitely abundant in nature, which stimulates scientists to create new materials with inventive uses and minimal environmental impact. Due to the various benefits of natural carbon dots (NCDs) from them has received a lot of attention recently. Natural products-derived carbon dots have recently emerged as a highly promising class of nanomaterials, showcasing exceptional properties and eco-friendly nature, which make them appealing for diverse applications in various fields such as biomedical, environmental sensing and monitoring, energy storage and conversion, optoelectronics and photonics, agriculture, quantum computing, nanomedicine and cancer therapy. Characterization techniques such as Photoinduced electron transfer, Aggregation-Induced-Emission (AIE), Absorbance, Fluorescence in UV-Vis and NIR Regions play crucial roles in understanding the structural and optical properties of Carbon dots (CDs). The exceptional photoluminescence properties exhibited by CDs derived from natural products have paved the way for applications in tissue engineering, cancer treatment, bioimaging, sensing, drug delivery, photocatalysis, and promising remarkable advancements in these fields. In this review, we summarized the various synthesis methods, physical and optical properties, applications, challenges, future prospects of natural products-derived carbon dots etc. In this expanding sector, the difficulties and prospects for NCD-based materials research will also be explored.

Investigation of the anti-cancer potential of epoxyazadiradione in neuroblastoma: experimental assays and molecular analysis.

Neuroblastoma, the most common childhood solid tumor, originates from primitive sympathetic nervous system cells. Epoxyazadiradione (EAD) is a limonoid derived from Azadirachta indica, belonging to the family Meliaceae. In this study, we isolated the EAD from Azadirachta indica seed and studied the anti-cancer potential against neuroblastoma. Herein, EAD demonstrated significant efficacy against neuroblastoma by suppressing cell proliferation, enhancing the rate of apoptosis and cycle arrest at the SubG0 and G2/M phases. EAD enhanced the pro-apoptotic Caspase 3 and Caspase 9 and inhibited the NF-kß translocation in a dose-dependent manner. In order to identify the specific EAD target, a gel-free quantitative proteomics study on SH-SY5Y cells using Liquid Chromatography with tandem mass spectrometry was done in a dose-dependent manner, followed by detailed bioinformatics analysis to identify effects on protein. Proteomics data identified that Enolase1 and HSP90 were up-regulated in neuroblastoma. EAD inhibited the expression of Enolase1 and HSP90, validated by mRNA expression, immunoblotting, Enolase1 and HSP90 kit and flow-cytometry based bioassay. Molecular docking study, Molecular dynamic simulation, and along with molecular mechanics/Poisson-Boltzmann surface area analysis also suggested that EAD binds at the active site of the proteins and were stable throughout the 100 ns Molecular dynamic simulation study. Overall, this study suggested EAD exhibited anti-cancer activity against neuroblastoma by targeting Enolase1 and HSP90 pathways.Communicated by Ramaswamy H. Sarma.

Normal weight central obesity and hypertension in India: Cross-sectional finding from LASI, 2017-19.

BACKGROUND AND AIM: The current public health guidelines for preventing and managing obesity still emphasize the importance of maintaining a normal Body Mass Index, while paying little attention to central obesity, which is common among the general population. Normal Weight Central Obesity (NWCO) is a less explored risk factor for hypertension in India. Therefore, this study aims to investigate the prevalence of NWCO and its association with hypertension in India. METHODS AND RESULTS: The cross-sectional study used data from the Longitudinal Aging Study in India (LASI), 2017-19, which included 54,016 participants (22,438 men and 31,578 women). Hypertension was evaluated following the JNC-VIII guidelines for the detection, evaluation, and treatment of hypertension. Anthropometric measurements were taken to identify NWCO. The study found that NWCO was more prevalent among women (33.9%) than men (17.8%), while men had a higher prevalence of hypertension (47.6%) than women (43.8%). In India, the state of Haryana had the highest proportion of NWCO among men (26.4%), while Kerala had the highest proportion among women (39.1%). Binary logistic regression analysis showed that NWCO was significantly associated with an increased risk of hypertension. The odds ratio (aOR) was 1.57 (95% CI 1.45-1.67, p < 0.001) in men and 1.53 (95% CI 1.43-1.63, p < 0.001) in women, compared to normal-weight study participants. CONCLUSIONS: The study emphasizes the importance of considering central obesity in individuals with a normal BMI when assessing cardiovascular risk, particularly for hypertension. State-specific data can help identify high-risk areas and facilitate targeted prevention and treatment strategies.

Combination of terlipressin and noradrenaline versus terlipressin in hepatorenal syndrome with early non-response to terlipressin infusion: A randomized trial.

BACKGROUND: Terlipressin and noradrenaline are effective in the management of hepatorenal syndrome (HRS). There are no reports on the combination of these vasoconstrictors in type-1 HRS. AIM: To evaluate terlipressin with or without noradrenaline in type-1 HRS not responding to terlipressin at 48 hours. METHODS: Sixty patients were randomized to receive either terlipressin (group A; n = 30) or a combination of terlipressin and noradrenaline infusion (group B; n = 30). In group A, terlipressin infusion was started at 2 mg/day and increased by 1 mg/day (maximum 12 mg/day). In group B, terlipressin was given at a constant dose of 2 mg/day. Noradrenaline infusion was started at 0.5 mg/h at baseline and increased to 3 mg/h in a stepwise manner. The primary outcome was treatment response at 15 days. Secondary outcomes were 30-day survival, cost-benefit analysis and adverse events. RESULTS: There was no significant difference in the response rate between the groups (50% vs. 76.7%, p = 0.06) and 30-day survival was similar (36.7% vs. 53.3%, p = 0.13). Treatment was more expensive in group A (USD 750 vs. 350, p < 0.001). Adverse events were more frequent in group A (36.7% vs. 13.3%, p < 0.05). CONCLUSIONS: The combination of noradrenaline and terlipressin infusion results in a non-significantly higher rate of HRS resolution with significantly fewer adverse effects in HRS patients who do not respond to terlipressin within 48 hours. CLINICALTRIALS: gov (NCT03822091).

Self-reported perceived stress, depression, and generalized anxiety disorder among Kathak dancers and physically active non-dancers of North India.

The aim of the present paper was to study the various common mental disorders in a sample of Kathak dancers and non-dancers of North India. 206 female Kathak dancers and 235 healthy controls, aged 18-45 years completed questionnaires assessing perceived stress (PSS-10), depressive symptoms (PHQ-9), and generalized anxiety (GAD-7). Pearson correlations assessed the association between perceived stress, depression, generalized anxiety, age, and years of dancing, and binary logistic regression identified the risk of developing depression and generalized anxiety disorder in Kathak dancers and non-dancers. The prevalence of perceived stress was similar among Kathak dancers and non-dancers. Kathak dancers reported significantly lower depressive symptoms compared to controls. Non-dancers with elevated perceived stress levels were 4 times more likely to report depressive symptoms and 7 times more likely to report anxiety symptoms, relative to dancers. The adjusted odds of reporting depressive symptoms along with generalized anxiety were higher among non-dancers compared to dancers. Kathak can be developed into a very effective psychotherapeutic tool for mitigating the risk of developing depression and generalized anxiety disorder.

In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line.

Natural products are being targeted as alternative anticancer agents due to their non-toxic and safe nature. The present study was conducted to explore the in vitro anticancer potential of Justicia adhatoda (J. adhatoda) leaf extract. The methanolic leaf extract was prepared, and the phytochemicals and antioxidant potential were determined by LCMS analysis and DPPH radical scavenging assay, respectively. A docking study performed with five major alkaloidal phytoconstituents showed that they had a good binding affinity towards the active site of NF-κB. Cell viability assay was carried out in five different cell lines, and the extract exhibited the highest cytotoxicity in MCF-7, a breast cancer cell line. Extract-treated cells showed a significant increase in nitric oxide and reactive oxygen species production. Cell cycle analysis showed an arrest in cell growth at the Sub-G0 phase. The extract successfully inhibited cell migration and colony formation and altered mitochondrial membrane potential. The activities of superoxide dismutase and glutathione were also found to decrease in a dose-dependent manner. The percentage of apoptotic cells was found to increase in a dose-dependent manner in MCF-7 cells. The expressions of caspase-3, Bax, and cleaved-PARP were increased in extract-treated cells. An increase in the expression of NF-κB was found in the cytoplasm in extract-treated cells. J. adhatoda leaf extract showed a potential anticancer effect in MCF-7 cells.

Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis.

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1ß, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1ß, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome.

Easy efficient HDR-based targeted knock-in in Saccharomyces cerevisiae genome using CRISPR-Cas9 system.

During the last two decades, yeast has been used as a biological tool to produce various small molecules, biofuels, etc., using an inexpensive bioprocess. The application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) techniques in yeast genetic and metabolic engineering has made a paradigm shift, particularly with a significant improvement in targeted chromosomal integration using synthetic donor constructs, which was previously a challenge. This study reports the CRISPR-Cas9-based highly efficient strategy for targeted chromosomal integration and in-frame expression of a foreign gene in the genome of Saccharomyces cerevisiae (S. cerevisiae) by homology-dependent recombination (HDR); our optimized methods show that CRISPR-Cas9-based chromosomal targeted integration of small constructs at multiple target sites of the yeast genome can be achieved with an efficiency of 74%. Our study also suggests that 15 bp microhomology flanked arms are sufficient for 50% targeted knock-in at minimal knock-in construct concentration. Whole-genome sequencing confirmed that there is no off-target effect. This study provides a comprehensive and streamlined protocol that will support the targeted integration of essential genes into the yeast genome for synthetic biology and other industrial purposes.Highlights• CRISPR-Cas9 based in-frame expression of foreign protein in Saccharomyces cerevisiae using Homology arm without a promoter.• As low as 15 base pairs of microhomology (HDR) are sufficient for targeted integration in Saccharomyces cerevisiae.• The methodology is highly efficient and very specific as no off-targeted effects were shown by the whole-genome sequence.

Screening of Azadirachta indica phytoconstituents as GSK-3ß inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study.

Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, primary regulator of various cellular activities varying from glycogen metabolism to cell proliferation and regulation. GSK-3ß is associated with the pathogenesis of numerous human diseases, including cancer, metabolic disorder, and Alzheimer's disease. In this study, Azadirachta indica compounds were selected and further screened on the BOILED-Egg model. The compounds showing good GIT absorption were docked with the crystal structure of GSK-3ß. The compounds with high docking score were submitted for the molecular dynamic simulation (MDS) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA). Based upon the MDS and MM-PBSA study, gedunin showed the highest binding energy throughout the MDS process. Gedunin was isolated from the Azadirachta indica, and its efficacy on GSK-3ß inhibition was studied in the human neuroblastoma (SH-SY5Y) cells. Gedunin induced apoptosis and anti-proliferative activity by arresting G2/M phase, as evident by cell-cycle analysis. From immunoblot study, gedunin significantly enhanced the expression of an inhibitory form of GSK-3ß (p-GSK-3ß Ser9) in concentration-dependent manner. Our findings demonstrate that gedunin may act as an effective GSK-3ß inhibitor suggesting that this compound may be used for the management of neuroblastoma. Further preclinical and clinical investigation is desirable.Communicated by Ramaswamy H. Sarma.

Computational screening of FDA approved drugs of fungal origin that may interfere with SARS-CoV-2 spike protein activation, viral RNA replication, and post-translational modification: a multiple target approach.

Coronavirus spread is an emergency reported globally, and a specific treatment strategy for this significant health issue is not yet identified. COVID-19 is a highly contagious disease and needs to be controlled promptly as millions of deaths have been reported. Due to the absence of proficient restorative alternatives and preliminary clinical restrictions, FDA-approved medications can be a decent alternative to deal with the coronavirus malady (COVID-19). The present study aims to meet the imperative necessity of effective COVID-19 drug treatment with a computational multi-target drug repurposing approach. This study focused on screening the FDA-approved drugs derived from the fungal source and its derivatives against the SARS-CoV-2 targets. All the selected drugs showed good binding affinity towards these targets, and out of them, bromocriptine was found to be the best candidate after the screening on the COVID-19 targets. Further, bromocriptine is analyzed by molecular simulation and MM-PBSA study. These studies suggested that bromocriptine can be the best candidate for TMPRSS2, Main protease, and RdRp protein. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00089-8.

Sensitivity and specificity of neuroimaging signs in patients with idiopathic intracranial hypertension.

BACKGROUND: The primary role of neuroimaging in idiopathic intracranial hypertension (IIH) is to exclude secondary causes of raised intracranial pressure. Recently, a few imaging markers have been described which may suggest diagnosis of IIH in atypical cases. We carried out this study to assess the prevalence and accuracy of these neuroimaging signs in predicting the diagnosis of IIH. METHODS: Eighty treatment-naive patients with IIH and 30 controls were recruited as per a predefined criterion. Magnetic resonance imaging (MRI) brain with detailed sella imaging was done in all patients. RESULTS: The most common abnormality noted was optic nerve tortuosity in 82.5% of patients, followed by posterior scleral flattening in 80%, perioptic subarachnoid space (SAS) dilatation in 73.8% and partial empty sella in 68.8% of patients. The presence of optic nerve tortuosity was the most sensitive sign on neuroimaging, though the highest specificity was seen for posterior scleral flattening and perioptic SAS dilatation. The presence of more than three neuroimaging features correlated with severity of vision loss. CONCLUSION: In suggestive clinical scenarios, posterior scleral flattening, perioptic SAS dilatation and optic nerve tortuosity are highly sensitive and specific signs in IIH. This study also highlights the utility of MRI as a valuable tool for prognosis of visual outcome in patients with IIH.

Application of CRISPR/Cas System in the Metabolic Engineering of Small Molecules.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas protein technology area is rapidly growing technique for genome editing and modulation of transcription of several microbes. Successful engineering in microbes requires an emphasis on the aspect of efficiency and targeted aiming, which can be employed using CRISPR/Cas system. Hence, this type of system is used to modify the genome of several microbes such as yeast and bacteria. In recent years, CRISPR/Cas systems have been chosen for metabolic engineering in microbes due to their specificity, orthogonality, and efficacy. Therefore, we need to review the scheme which was acquired for the execution of the CRISPR/Cas system for the modification and metabolic engineering in yeast and bacteria. In this review, we highlighted the application of the CRISPR/Cas system which has been used for the production of small molecules in the microbial system that is chemically and biologically important.

Disordered eating attitudes and body shape concerns among North Indian Kathak dancers.

OBJECTIVE: To determine the prevalence and association between disordered eating attitudes and body shape concerns in a sample of North Indian Kathak dancers. METHOD: Participants were 206 Kathak female dancers and 235 healthy controls, ages 18-45 years. Participants completed questionnaires assessing demographics, disordered eating attitudes, and body dissatisfaction. Pearson correlations assessed the association between the disordered eating attitudes and body dissatisfaction, and binary logistic regression identified the risk of having a possible eating disorder. RESULTS: Kathak dancers reported significantly greater disordered eating attitudes compared to controls (12.1% vs. 5.9%, p = .023). Dancers endorsed greater dieting behaviors (M = 5.6 vs. 4.5, p = .031), and binge eating episodes (p < .001) relative to their counterparts. Body dissatisfaction was significantly positively correlated with disordered eating attitudes among the dancers (p < .001). Dancers with elevated body shape concerns were five times more likely to report disordered eating attitudes, relative to their peers (p < .001). DISCUSSION: Disordered eating attitudes and body shape concerns are prevalent among North Indian Kathak dancers. Future research should aim to develop targeted prevention and intervention programs that focus on reducing these behaviors and promoting a positive body image to mitigate the risk of disordered eating among this group.

Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study.

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.

Epigenetic modification and therapeutic targets of diabetes mellitus.

The prevalence of diabetes and its related complications are increasing significantly globally. Collected evidence suggested that several genetic and environmental factors contribute to diabetes mellitus. Associated complications such as retinopathy, neuropathy, nephropathy and other cardiovascular complications are a direct result of diabetes. Epigenetic factors include deoxyribonucleic acid (DNA) methylation and histone post-translational modifications. These factors are directly related with pathological factors such as oxidative stress, generation of inflammatory mediators and hyperglycemia. These result in altered gene expression and targets cells in the pathology of diabetes mellitus without specific changes in a DNA sequence. Environmental factors and malnutrition are equally responsible for epigenetic states. Accumulated evidence suggested that environmental stimuli alter the gene expression that result in epigenetic changes in chromatin. Recent studies proposed that epigenetics may include the occurrence of 'metabolic memory' found in animal studies. Further study into epigenetic mechanism might give us new vision into the pathogenesis of diabetes mellitus and related complication thus leading to the discovery of new therapeutic targets. In this review, we discuss the possible epigenetic changes and mechanism that happen in diabetes mellitus type 1 and type 2 separately. We highlight the important epigenetic and non-epigenetic therapeutic targets involved in the management of diabetes and associated complications.