Omicron, a new SARS-CoV-2 variant: assessing the impact on severity and vaccines efficacy.

The reply letter has been put forth in response to the comment made by Karthyayani Priya Satish entitled "India and the COVID-19 Vaccine." The comment was made in context to our published work "Exploring the covid-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?" The reply letter is concerned with the newer variant of SARS-CoV-2, i.e.

Exploring the COVID-19 vaccine candidates against SARS-CoV-2 and its variants: where do we stand and where do we go?

As of September 2021, 117 COVID-19 vaccines are in clinical development, and 194 are in preclinical development as per the World Health Organization (WHO) published draft landscape. Among the 117 vaccines undergoing clinical trials, the major platforms include protein subunit; RNA; inactivated virus; viral vector, among others. So far, USFDA recognized to approve the Pfizer-BioNTech (Comirnaty) COVID-19 vaccine for its full use in individuals of 16 years of age and older.

Recent efforts for drug identification from phytochemicals against SARS-CoV-2: Exploration of the chemical space to identify druggable leads.

Nature, which remains a central drug discovery pool, is always looked upon to find a putative druggable lead. The natural products and phytochemical derived from plants are essential during a global health crisis. This class represents one of the most practical and promising approaches to decrease pandemic's intensity owing to their therapeutic potential.

Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update.

The review summarizes chloroquine (CQ) and its safer derivative hydroxychloroquine (HCQ) and its utility in Covid-19. Recently this well-established drug made its way back to the headlines during the SARS-CoV-2 pandemic. This led to an upsurge in the scientific arena with multiple research and review articles along with expert opinions and commentaries.

Exploring the magic bullets to identify Achilles' heel in SARS-CoV-2: Delving deeper into the sea of possible therapeutic options in Covid-19 disease: An update.

The symptoms associated with Covid-19 caused by SARS-CoV-2 in severe conditions can cause multiple organ failure and fatality via a plethora of mechanisms, and it is essential to discover the efficacious and safe drug. For this, a successful strategy is to inhibit in different stages of the SARS-CoV-2 life cycle and host cell reactions. The current review briefly put forth the summary of the SARS-CoV-2 pandemic and highlight the critical areas of understanding in genomics, proteomics, medicinal chemistry, and natural products derived drug discovery.

Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines.

A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration.

Drugs targeting various stages of the SARS-CoV-2 life cycle: Exploring promising drugs for the treatment of Covid-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense, single-stranded RNA virus that causes the potentially lethal Covid-19 respiratory tract infection. It does so by binding to host cell angiotensin converting enzyme 2 (ACE2) receptors, leading to endocytosis with the receptor, and subsequently using the host cell's machinery to replicate copies of itself and invade new cells. The extent of the spread of infection in the body is dependent on the pattern of ACE2 expression and overreaction of the immune system.

Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles.

Polymeric nanoparticles (PNPs) are a promising platform for drug, gene, and vaccine delivery. Although generally regarded as safe, the toxicity of PNPs is not well documented. The present study investigated in vitro toxicity of poly-ε-caprolactone, poly(DL-lactic acid), poly(lactide-cocaprolactone), and poly(lactide-co-glycide) NPs and possible mechanism of toxicity.

Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles.

Silver nanoparticles (Ag NPs) are used in consumer products and wound dressings due to their antimicrobial properties. However, in addition to toxic effects on microbes, Ag NPs can also induce stress responses as well as cytotoxicity in mammalian cells. We observed that Ag NPs are efficiently internalized via scavenger receptor-mediated phagocytosis in murine macrophages.

Insulin resistance induces a segmental difference in thoracic and abdominal aorta: differential expression of AT1 and AT2 receptors.

Objectives: The study was pursued to understand and compare the vascular reactivity to angiotensin II (Ang II) and its receptor expression in thoracic and abdominal aorta under insulin resistance.

Methods: Vascular reactivity to Ang II was recorded isometrically, AT1/AT2 receptor gene and protein expression was checked by RT-PCR and western blotting, respectively, and abundance of phospho (serine-10 Ph) H3 on promoter regions of Agtr1/Agtr2 genes was done by chromatin immunoprecipitation assay in aortic rings isolated from high fat diet (HFD)-fed rats.

Results: Our functional studies showed an increased (Emax in mg/mm: Con: 319 ± 29 and HFD: 1095 ± 72, P < 0.

Furosemide-induced genotoxicity and cytotoxicity in the hepatocytes, but weak genotoxicity in the bone marrow cells of mice.

Furosemide (FS) is a potent loop diuretic widely used in the management of fluid retention associated with cardiac, renal, and hepatic failure as well as for the treatment of hypertension. FS is a well-characterized and known hepatotoxin in both human and animal test systems. In this study, an attempt has been made to investigate the in vivo genotoxicity of FS at the hepatotoxic equivalent doses using the chromosomal aberration and the comet assay in the bone marrow cells of mice as the endpoints of evaluation.

Insulin-resistance reduces botulinum neurotoxin-type A induced prostatic atrophy and apoptosis in rats.

Botulinum neurotoxin-type A (BoNTA) is an emerging therapeutic option for the treatment of benign prostatic hyperplasia. Recent reports indicate increased incidence of benign prostatic hyperplasia in the insulin-resistant individuals. Insulin-resistance is associated with the compensatory rise in the plasma insulin, which is known to have growth-promoting effects.

Pioglitazone attenuates prostatic enlargement in diet-induced insulin-resistant rats by altering lipid distribution and hyperinsulinaemia.

Background And Purpose: Increased incidence of benign prostatic hyperplasia among insulin-resistant individuals suggests a role for hyperinsulinaemia in prostatic enlargement. We have already reported increased cell proliferation and enlargement of prostate gland in insulin-resistant rats. The present study aimed to elucidate the molecular mechanisms underlying the reversal of prostatic enlargement in insulin-resistant rats by the peroxisome proliferator-activated receptor γ agonist pioglitazone.

Use of chemoprotectants in chemotherapy and radiation therapy: the challenges of selecting an appropriate agent.

Chemoprotection refers to the protection from the toxicity of one chemical by the intervention of another. Conflicting preclinical and clinical reports make it difficult to either ignore or accept the use of chemoprotectants during cancer chemotherapy or radiotherapy. The selection of anticancer drugs depends on the type and stage of cancer development.

Insulin-resistance and benign prostatic hyperplasia: the connection.

Benign prostatic hyperplasia (BPH) is a highly prevalent disease in the aged men population characterized by augmented cell proliferation and contractility of the prostate gland. Prior studies have demonstrated the relationship between BPH and insulin-resistance syndrome. During insulin-resistance, hyperinsulinemia develops to combat the decreased responsiveness of the body towards insulin.

Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro.

Carbamazepine (CBZ), one of the most commonly prescribed antiepileptic drug, is proposed to inhibit Na+ channel. In this study, we have investigated the effects of CBZ on Na+ current, evoked in cultured dorsal root ganglion (DRG) neurons from neonatal rats using whole cell patch clamp technique. In small DRG neurons (20-25 microm), Na+ current was obtained by blocking K+ and Ca2+ currents with appropriate ion replacement and channel blockers.

Predictors of metabolic syndrome in Asian north Indians with newly detected type 2 diabetes.

Background & Objective: The identification of metabolic syndrome (MS) among patients with type 2 diabetes (T2DM) is of great importance, since those with MS carry a cluster of cardiovascular risk factors. This study evaluates suitable criteria with high efficiency in diagnosing MS and to identify the strongest predictors of MS in newly detected type 2 diabetes individuals.

Methods: Newly detected type 2 diabetes (<6 months) patients were assessed.

Influence of hyperglycaemia on chemical-induced toxicity: study with cyclophosphamide in rat.

Diabetes mellitus is a metabolic disorder characterized by elevated level of glucose in the blood. Hyperglycaemia perturbs the critical balance between oxidative stress and anti-oxidant defence mechanisms in the body and thereby alters the response of biological system towards various toxic chemicals. Cyclophosphamide (CP) is a widely prescribed anticancer drug, well-known genotoxic agent as well as used in the development of immunocompromised animal models.

Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

Background: Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA.

Prevalence and predictors of metabolic syndrome in non-obese Asian Indians with newly detected type 2 diabetes mellitus.

We measured the prevalence and have evaluated the sensitivity, specificity, positive and negative predictive value of different predictors according to different standard criteria for metabolic syndrome in non-obese newly detected type 2 diabetes. Two hundred and fifteen patients of BMI <25 kg/m2 were studied. Metabolic syndrome prevalence was high in non-obese newly detected type 2 diabetes mellitus individuals.

New PPARgamma ligands based on barbituric acid: virtual screening, synthesis and receptor binding studies.

A new series of PPARgamma ligands based on barbituric acid (BA) has been designed employing virtual screening and molecular docking approach. To validate the computational approach, designed molecules were synthesized and evaluated in in vitro radioligand binding studies. Out of the total 14 molecules, 6 were found to bind to the murine PPARgamma with IC(50) ranging from 0.

Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats.

The present study was designed to test the hypothesis that insulin resistance plays a role in high fat diet feeding induced cognitive deficits. Rats consuming the high fat diet exhibited characteristic features of insulin resistance viz. mild hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and hyperinsulinemia.

New PPARgamma ligands based on 2-hydroxy-1,4-naphthoquinone: computer-aided design, synthesis, and receptor-binding studies.

FlexX-based molecular docking study was employed to identify 2-hydroxy-1,4-naphthoquinone as a new 'acidic head group' for the design of a novel series of PPARgamma ligands. To provide the proof of concept, designed molecules were synthesized and evaluated in a standard radioligand-binding assay. Out of eight molecules, four were found to bind to the murine PPARgamma with IC(50) ranging from 0.

Protective effects of American ginseng (Panax quinquefolium) against mitomycin C induced micronuclei in mice.

Mitomycin C (MMC) is a highly active anticancer drug commonly used alone and in combination with other chemotherapeutic agents for the treatment of different cancers. Its bioactivated form critically damages the DNA present in both rapidly dividing cancerous cells as well as in normal cells. Genotoxicity in the normal cells makes this drug highly toxic; thereby decreasing its therapeutic index for clinical use.

Prior bleeding enhances the sensitivity of peripheral blood and bone marrow micronucleus tests in rats.

The rat peripheral blood micronucleus (MN) assay is not considered to be a sufficient biomarker of genotoxin exposure due to the selective elimination of micronucleated cells from peripheral circulation by the spleen. However, several recent reports suggest that peripheral blood reticulocytes of rats may represent a suitable cell population for use in the MN assay. The MN assay in rats with prior bleeding was thus conducted to determine the sensitivity of the bioassay.