SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach.

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR ß gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors' matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

Zingerone induced caspase-dependent apoptosis in MCF-7 cells and prevents 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in experimental rats.

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12-dimethylbenz(a)anthracene (DMBA)-treated mammary carcinogenesis in Sprague-Dawley (SD) rats and MCF-7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA-induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt-b5 and CYP450 ) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl-2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA-induced mammary cancer in SD animals and Michigan cancer foundation-7 mammary cancer cells.

ChatGPT in Pediatrics: Unraveling its Significance as a Clinical Decision Support Tool.

The integration of artificial intelligence in pediatrics holds transformative potential, reshaping healthcare through innovative approaches to diagnosis, treatment planning, and tailored clinical decision support. In the evaluation of ChatGPT's performance in pediatric case scenarios, the model displayed varying levels of proficiency suggesting the need for continuous refinement and collaboration with senior pediatricians for reliable pediatric decision support.

An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients.

Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been presented as a broad-spectrum antiviral agent. This randomised clinical trial in a hospital setting evaluated the efficacy and safety of this drug in RT-PCR-positive coronavirus disease 2019 (COVID-19) patients. A total of 210 RT-PCR-positive COVID-19 patients who provided consent were allotted to the control or case arm, based on block randomisation. The control arm received standard of care comprising paracetamol, ivermectin, and other adjuvant therapies. The patients in the case arm received indomethacin instead of paracetamol, with other medications retained. The primary endpoint was the development of hypoxia/desaturation with SpO2 ≤ 93, while time to become afebrile and time for cough and myalgia resolution were the secondary endpoints. The results of 210 patients were available, with 103 and 107 patients in the indomethacin and paracetamol arms, respectively. We monitored patient profiles along with everyday clinical parameters. In addition, blood chemistry at the time of admission and discharge was assessed. As no one in either of the arms required high-flow oxygen, desaturation with a SpO2 level of 93 and below was the vital goal. In the indomethacin group, none of the 103 patients developed desaturation. On the other hand, 20 of the 107 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief than those in the paracetamol arm, with most symptoms disappearing in half the time. In addition, 56 out of 107 in the paracetamol arm had fever on the seventh day, while no patient in the indomethacin group had fever. Neither arm reported any adverse event. The fourteenth-day follow-up revealed that the paracetamol arm patients had faced several discomforts; indomethacin arm patients mostly complained only of tiredness. Indomethacin is a safe and effective drug for treating patients with mild and moderate covid-19.

A Computational approach to screen, predict and annotate human and chimpanzee PHEX intronic miRNAs, their gene targets, and regulatory interaction networks.

The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insight about the human-chimpanzee relatedness that could influence the development of new treatments and diagnostic aids for various ailments. Especially, more than 300 diseases have been mapped to the X chromosome, which has unique and complicated characteristics than other chromosomes in the human genome. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. Therefore, this evolutionary-based genome annotation study attempted to computationally compare, contrast, and annotate the homologous miRNAs and their gene regulatory mechanisms in the intronic regions of the PHEX gene on the human X chromosome of the two species. From our results, we identified a total of 1296 human miRNAs and 46, 957 gene targets. Similarly, 30, 563 targets of homologous chimp miRNAs were predicted. miRNAs like hsa-miR-17-5p showed a maximum number of interactions while miRNAs like hsa-miR-107 with the least number of interactions in the human/chimp gene networks. A few top-ranked miRNAs such as hsa-miR-24, hsa-miR-145, hsa-miR-34a, and hsa-miR-378 were observed to be common between the two genera. The cooperativity and multiplicity of certain miRNAs were predicted to regulate the expression of diverse cancer-associated genes such as Cyclin D1, Notch1, CDK-6, E2F3, ALK4, CKDN2A, DHFR, and MAPK14. Nevertheless, further in vitro and in vivo experimental validations of these gene candidates are required before they could be used as potential diagnostic markers and drug targets.

Effect of webinars in teaching-learning process in medical and allied health science students during COVID-19 pandemic: A cross-sectional study.

BACKGROUND: COVID-19 pandemic lockdown has brought all sectors to be dwindled with no exception of the academic system. Even professional courses like medical and allied health academic courses were also not spared. The academic requirements were not met as required to do so. Webinar has become a good source of virtual platform acting as a bridge for attaining the gaps in accomplishing the curriculum to the students during these curfew times. Our study aimed to know the value of webinars on teaching-learning processes among the medical and allied health science students in India. MATERIALS AND METHODS: The study design is a cross-sectional study with 2084 students who attended at least one webinar. An online survey questionnaire was sent, and the data were collected on participant's perspective on the effectiveness of webinar, post webinar assessment by their satisfactory level of gain of information through webinars and their plan to apply in future. RESULTS: Participant's perspective on effectiveness of webinar showed 66.7% of agreement with the webinar use. In post webinar assessment, the use of webinar was in agreement with 69.9% of the participants. Furthermore, we observed a significant association with the gain of information in post webinar assessment (P < 0.05) and a significant association with their plan to apply in future (P < 0.05). CONCLUSION: Our results showed that the students were satisfied with the webinar teaching and acknowledged it to be an effective tool in the teaching-learning process to gain new knowledge and wish to attend webinars in future as a part of their curriculum. Thus, webinars have a constructive effect in the teaching and learning process in professional courses during pandemic lockdown.

Polysaccharide-Drug Conjugates: A Tool for Enhanced Cancer Therapy.

Cancer is one of the most widespread deadly diseases, following cardiovascular disease, worldwide. Chemotherapy is widely used in combination with surgery, hormone and radiation therapy to treat various cancers. However, chemotherapeutic drugs can cause severe side effects due to non-specific targeting, poor bioavailability, low therapeutic indices, and high dose requirements. Several drug carriers successfully overcome these issues and deliver drugs to the desired sites, reducing the side effects. Among various drug delivery systems, polysaccharide-based carriers that target only the cancer cells have been developed to overcome the toxicity of chemotherapeutics. Polysaccharides are non-toxic, biodegradable, hydrophilic biopolymers that can be easily modified chemically to improve the bioavailability and stability for delivering therapeutics into cancer tissues. Different polysaccharides, such as chitosan, alginates, cyclodextrin, pullulan, hyaluronic acid, dextran, guar gum, pectin, and cellulose, have been used in anti-cancer drug delivery systems. This review highlights the recent progress made in polysaccharides-based drug carriers in anti-cancer therapy.

The Association of Latitude and Altitude with COVID-19 Symptoms: A VIRUS: COVID-19 Registry Analysis.

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. Objectives: To study the association of latitude and altitude with COVID-19 symptomatology. Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering. Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms (p<.001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude (p=.026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively). Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude.

Molecular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus.

It is of interest to document the moelcular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.

Molecular docking of alkaloid compounds with the matrix metalloproteinase 2.

Matrix metalloproteinase protein-2 (MMP-2) is linked to the human oral squamous cell carcinoma. Therefore, it is of interest to design new inhibitors for MMP-2 to combat the disease. Thus, we document the molecular docking features of Aristolochic acid, Cryptopleurine, Epipodophyllotoxin, and Fagaronine with MMP-2 for further consideration.

Tomentosin Reduces Behavior Deficits and Neuroinflammatory Response in MPTP-Induced Parkinson's Disease in Mice.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Tomentosin is an active compound isolated from the I. viscosa plant that has extensive therapeutic value. In this exploration, the neuroprotective actions of tomentosin were investigated against MPTP-stimulated neuroinflammation in mice. PD was stimulated in C57/BL6 mice by injecting 20-mg/kg MPTP at 2-h intervals 4 times a day for 15 days simultaneously with tomentosin treatment. The rota-rod test, grasping test, and pole climbing test were executed to investigate the motor functioning of the test animals. Proinflammatory cytokines, reactive oxygen species, and myeloperoxidase were assayed using commercial ELISA kits. Superoxide dismutase enzyme levels were measured by the standard method. Expression of TLR-4/NF-κB was analyzed by Western blot. Brain tissues of investigational animals were analyzed microscopically. Tomentosin treatment of the MPTP-intoxicated PD mice promoted appreciable regains in body weight and noticeably prevented MPTP-stimulated impairments in motor function. In the PD mice, proinflammatory cytokine, ROS, and MPO levels were lowered by tomentosin, inhibited the TLR-4/NF-κB signaling pathway and prevented inflammation-mediated neuronal cell damage, and reduced glial cell damage and normalized ganglion layers. These findings confirmed the neuroprotective properties of tomentosin against MPTP-induced PD in mice.

Molecular docking data of E3 ubiquitin-protein ligase WWP1 with compounds from a medicinal plant Justicia adhatoda L.

It is known that E3 ubiquitin-protein ligase WWP1 is linked to oral cancer. Therefore, it is of interest to document molecular docking data of E3 ubiquitin-protein ligase WWP1 with compounds ((Stigmasterol, Pyrazinamide, Vasicinone and Ethambutol)) from a medicinal plant Justicia adhatoda L for further consideration.

Molecular modeling of cornulin (CRNN) for docking with phytocompounds from Justicia adhatoda L.

Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds (Pyrazinamide, Anisotine, Vasicinone, Vasicoline) from Justicia adhatoda L. Thus, we document the optimal binding features of these compounds with the cornulin model for further consideration.

Molecular docking of potential inhibitors with the mTOR protein.

The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration.

Mitochondrial and Organellar Crosstalk in Parkinson's Disease.

Mitochondrial dysfunction is a well-established pathological event in Parkinson's disease (PD). Proteins misfolding and its impaired cellular clearance due to altered autophagy/mitophagy/pexophagy contribute to PD progression. It has been shown that mitochondria have contact sites with endoplasmic reticulum (ER), peroxisomes and lysosomes that are involved in regulating various physiological processes. In pathological conditions, the crosstalk at the contact sites initiates alterations in intracellular vesicular transport, calcium homeostasis and causes activation of proteases, protein misfolding and impairment of autophagy. Apart from the well-reported molecular changes like mitochondrial dysfunction, impaired autophagy/mitophagy and oxidative stress in PD, here we have summarized the recent scientific reports to provide the mechanistic insights on the altered communications between ER, peroxisomes, and lysosomes at mitochondrial contact sites. Furthermore, the manuscript elaborates on the contributions of mitochondrial contact sites and organelles dysfunction to the pathogenesis of PD and suggests potential therapeutic targets.

Osteogenic differentiation and mineralization potential of zinc oxide nanoparticles from Scutellaria baicalensis on human osteoblast-like MG-63 cells.

Development of biologically inspired green synthesis of silver nanoparticles has been extensively scrutinized owing to its uses in biomedical industry. In the last two decades, the demands of nanomaterial in bone remodelling have increased. Scutellaria baicalensis is a flowering plant usually used for many ailments. This work explores the zinc oxide nanoparticles (ZnO NPs) by green route method from S. baicalensis and the therapeutic potentials of Sb-ZnONPs on differentiation of osteoblast and osteoclast formation inhibition. The characterization of the fabricated ZnO-NPs from S. baicalensis was done via different spectroscopic and microscopic techniques; ultraviolet-visible spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Osteogenic-related tests (MTT, Mineralization assay and Real-time PCR) were used to evaluate the properties of SB-ZnONPs on the growth and proliferation of human osteoblast-like MG-63 cells. The characterization of SB-ZnONPs discovered the crystalline properties with high zinc content and the existence of bioactive mixtures from S. baicalensis extract. In addition, SB-ZnONPs showed insignificant cytotoxicity with enhanced differentiation, proliferation, and mineralization on MG-63 cells. Overall, these results denote that SB-ZnONPs is expected to be a natural source for the development of medical agents to in bone healing and remodelling.

Antiatherosclerotic Activity of Eriocitrin in High-Fat-Diet-Induced Atherosclerosis Model Rats.

Atherosclerosis is a multifactorial disease that develops and progresses in the arterial wall in response to a variety of stimuli. Among various other stimuli, hyperlipidemia is an extremely important factor that is correlated with the development of atherosclerosis. Lemon and citrus fruits contain various bioactive flavonoids, such as eriocitrin, that prevent obesity and related metabolic diseases. Therefore we concentrated on eriocitrin, a potent flavonoid with numerous therapeutic properties, particularly its beneficial lipid-lowering action in rats subjected to high fat diet. The anti-atherosclerotic efficacy of eriocitrin was assessed in rats administered a diet rich in fat. Wistar rats were divided into five groups consisting of six animals in all groups. Group I served the control, Group II was fed a high-fat diet (HFD), and the third and fourth groups were fed an HFD supplemented with varying doses of eriocitrin, and the last group was administered simvastatin for the last 30 days. Body weight, organ weight, lipid and lipoprotein parameters, cardiac and inflammatory markers, and histological examination were evaluated in animals induced with an HFD. Eriocitrin displayed a significant anti-atherosclerotic action by lowering the body weight, organ weight, reduction in lipid content, cardiac and inflammatory markers, myocardial changes confirmed by histopathology, malondialdehyde and increased antioxidant enzyme activities, nitric oxide, as well as 6-keto-PGF1α and high-density lipoprotein levels in rats fed an HFD. The findings of the experiment suggest that the anti-atherosclerotic action of eriocitrin was due to its modulatory activity in lipid metabolism. Considering the overall results of the study it can be validated that a use of flavonoid eriocitrin might be beneficial in altering HFD-induced alterations in atherosclerotic rats.