Effect of quercetin on steroidogenesis and folliculogenesis in ovary of mice with experimentally-induced polycystic ovarian syndrome.

Introduction: Polycystic Ovary syndrome (PCOS) affects the health of many women around theworld. Apart from fundamental metabolic problems connected to PCOS, focus of our study is on the role of quercetin on genes relevant to steroidogenesis and folliculogenesis. Methods: Eighteen mature parkes strain mice (4-5 weeks old) weighing18-21 g were randomly divided into three groups of six each as follows: Group I serves as the control and was given water and a regular chow diet ad lib for 66 days; group II was given oral gavage administration of letrozole (LETZ) (6 mg/kgbw) for 21 days to induce PCOS and was left untreated for 45 days; For three weeks, Group III received oral gavage dose of LETZ (6 mg/kg), after which it received Quercetin (QUER) (125 mg/kg bw orally daily) for 45 days. Results: In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH ratio, decreased estrogen level and decline in expression of Kitl, Bmp1, Cyp11a1, Cyp19a1, Ar, lhr, Fshr and Esr1 in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in cholesterol, triglycerides, testosterone, vascular endothelial growth factor VEGF and insulin levels. All these changes were reversed after the administration of quercetin in PCOS mice. Discussion: Quercetin treatment reversed the molecular, functional and morphological abnormalities brought on due to letrozole in pathological and physiological setting, particularly the issues of reproduction connected to PCOS. Quercetin doesn't act locally only but it acts systematically as it works on Pituitary (LH/FSH)- Ovary (gonad hormones) axis. the Side effects of Quercetin have to be targeted in future researches. Quercetin may act as a promising candidate for medical management of human PCOS.

Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing.

Biological macromolecules are excellent materials for wound dressing owing to their similar structure to the extracellular matrix and adjustable physicochemical properties. This research focuses on fabricating biological macromolecule-based hydrogel with desirable antibacterial, antioxidant, controlled drug release, cytocompatibility, and wound healing properties. Herein, different concentrations of nanoceria (NC) and flurbiprofen (FLU) drug-loaded gellan gum/gelatin (GG/Ge) based dual crosslinked (Ionic and EDC/NHS coupling) hydrogels were engineered. All fabricated hydrogels were hydrophilic, biodegradable, good strength, porous, antioxidant, hemocompatible and cytocompatible. Among all, hydrogel loaded with 500 µg/ml NC (GG/Ge/NC@FLU) exhibited desirable antioxidant, antibacterial (killed Staphylococcus aureus and Escherichia coli within 12 h), hemocompatible, cytocompatible, supports oxidative-stressed L929 cell growth and acted as a controlled release matrix for FLU, following Fickian diffusion, Peppas Sahlin and Korsmeyer-Peppas drug release models. Furthermore, nanocomposite hydrogel (GG/Ge/NC@FLU)-treated wounds of rats on day 14 demonstrated significantly higher collagen synthesis, nearly 100 % wound contractions, and efficiently decreased the expression of TNF-α and IL-1 while increasing the production of IL-10 and TNF-ß3, indicating antiinflammatory activity, and effectively reduced the expression of VEGF gene indicating effective angiogenesis than all other controls. In conclusion, the fabricated multifunctional GG/Ge/NC@FLU nanocomposite hydrogel shows promising potential for effectively treating full-thickness wound healing in a rat model.

Organoids: A new approach in toxicity testing of nanotherapeutics.

Nanotechnology has revolutionized diverse fields, which include agriculture, the consumer market, medicine, and other fields. Widespread use of nanotechnology-based products has led to increased prevalence of these novel formulations in the environment, which has raised concerns regarding their deleterious effects. The application of nanotechnology-based formulations into clinical use is hampered by the lack of the availability of effective in vitro systems, which could accurately assess their in vivo toxic effects. A plethora of studies has shown the hazardous effects of nanoparticle-based formulations in two-dimensional in vitro cell cultures and animal models. These have some associated disadvantages when used for the evaluation of nano-toxicity. Organoid technology fills the space between existing two-dimensional cell line culture and in vivo models. The uniqueness of organoids over other systems for evaluating toxicity caused by nano-drug formulation includes them being a co-culture of diverse cell types, dynamic flow within them that simulates the actual flow of nanoparticles within biological systems, extensive cell-cell, cell-matrix interactions, and a tissue-like morphology. Thus, it mimics the actual tissue microenvironment and, subsequently, provides an opportunity to study drug metabolism and toxico-dynamics of nanotechnology-based novel formulations. The use of organoids in the evaluation of nano-drug toxicity is in its infancy. A limited number of studies conducted so far have shown good predictive value and efficiently significant data correlation with the clinical trials. In this review, we attempt to introduce organoids of the liver, lungs, brain, kidney intestine, and potential applications to evaluate toxicity caused by nanoparticles.

Repurposing of Mycobacterium indicus pranii for the severe form of COVID-19 patients in India: A cohort study.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces the production of proinflammatory cytokines, which results in a cytokine storm, and immune-modulators like Mycobacterium indicus pranii (MIP) might ameliorate coronavirus disease of 2019 (COVID-19) related cytokine storm. Therefore, the present study evaluates whether MIP offers an advantage in the treatment of severe COVID-19 patients infected with SARS-CoV-2. A prospective MIP cohort study was conducted in chest disease hospitals in Srinagar, Jammu and Kashmir, India. In the present prospective, randomized clinical study, critically severe COVID-19 patients were divided into two groups, the MIP group (n = 105) and the best standard treatment (BST) group (n = 210). Procalcitonin, ferritin, high-sensitive C-reactive protein, D-dimer levels, and interleukin levels on 5th-day posttreatment were significantly reduced in the MIP group compared to the BST group. Compared to the BST group, 105 consecutive patients with severe COVID-19 in the MIP group reported early weaning off ventilation, resolution of chest architecture (computed tomography [CT] scan), a significant increase in SpO2 levels, and decreased mortality with a hazard ratio: 0.234 (95% confidence interval: 0.264-2.31) (p = 0.001). MIP restored SpO2 , immune/inflammatory response, normalized lung abnormalities (chest CT scan), and reduced mortality without any serious complications. However, there is a need for placebo-controlled double-blind and controlled clinical trials to confirm the efficacy.

An update on emerging therapeutics to combat COVID-19.

BACKGROUND: The COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19. OBSERVATIONS: Single-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19. CONCLUSION: The COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.

Medicinal plants: Treasure for antiviral drug discovery.

The pandemic of viral diseases like novel coronavirus (2019-nCoV) prompted the scientific world to examine antiviral bioactive compounds rather than nucleic acid analogous, protease inhibitors, or other toxic synthetic molecules. The emerging viral infections significantly associated with 2019-nCoV have challenged humanity's survival. Further, there is a constant emergence of new resistant viral strains that demand novel antiviral agents with fewer side effects and cell toxicity. Despite significant progress made in immunization and regenerative medicine, numerous viruses still lack prophylactic vaccines and specific antiviral treatments that are so often influenced by the generation of viral escape mutants. Of importance, medicinal herbs offer a wide variety of therapeutic antiviral chemotypes that can inhibit viral replication by preventing viral adsorption, adhering to cell receptors, inhibiting virus penetration in the host cell, and competing for pathways of activation of intracellular signals. The present review will comprehensively summarize the promising antiviral activities of medicinal plants and their bioactive molecules. Furthermore, it will elucidate their mechanism of action and possible implications in the treatment/prevention of viral diseases even when their mechanism of action is not fully understood, which could serve as the base for the future development of novel or complementary antiviral treatments.