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Pain is one of the clinical manifestations that can vary from mild to severe symptoms in COVID-19 patients. Pain symptoms can be initiated by direct viral damage to the tissue or by indirect tissue injury followed by nociceptor sensitization. The most common types of pain that are reported to occur in COVID-19 patients are headache, myalgia, and chest pain. With more and more cases coming in the hospitals, many new and unique symptoms of pain are being reported. Testicular and abdominal pain are rare cases of pain that are also being reported and are associated with COVID-19. The SARS-CoV-2 virus has a high affinity for angiotensin-converting enzyme-2 receptor (ACE-2) which acts as an entry point for the virus. ACE-2/ Ang II/AT 1 receptor also participates directly in the transmission of pain signals from the dorsal horn of the spinal cord. It induces a series of complicated responses in the human body. Among which the cytokinetic storm and hypercoagulation are the most prominent pathways that mediate the sensitization of sensory neurons facilitating pain. The elevated immune response is also responsible for the activation of inflammatory lipid mediators such as COX-1 and COX-2 enzymes for the synthesis of prostaglandins (PGs). PG molecules especially PGE2 and PGD2 are involved in the pain transmission and are found to be elevated in COVID-19 patients. Though arachidonic acid pathway is one of the lesser discussed topics in COVID-19 pathophysiology, still it can be useful for explaining the unique and rarer symptoms of pain seen in COVID-19 patients. Understanding different pain pathways is very crucial for the management of pain and can help healthcare systems to end the current pandemic situation. We herein review the role of various molecules involved in the pain pathology of COVID-19.

The article gives a general examination of artificial intelligence methods including support vector machines and artificial neural networks, as well as the key areas in which they are applied to the oil and gas sector. In this study, the interpretation of geological data, price forecasting, and flow regime forecasting are the three main applications of such technologies that are examined. The employment of artificial intelligence-based techniques improves the productivity of labour done in both exploration and production, allowing for better outcomes at a lower cost. Utilizing all possible mechanisms to increase efficiency is crucial in the changing market conditions created in the mining and energy sectors. At every level of the oil production process, data mining techniques are very practical.

Chronic pain is among the most burdensome and devastating disorders affecting millions of people worldwide. Recent studies suggest the role of kinesin nanomotors in development and maintenance of chronic pain. KIF17 is a member of kinesin superfamily that binds to NR2B cargo system via mLin10 scaffolding protein and makes the NMDARs functional at cell surface. NMDA receptor activation is known to induce the central sensitization and excitotoxicity which can be recognized by the glial cells followed by the release of cytokine storm at spinal and supraspinal level leading to chronic pain. In this study, we have investigated the role of aurora kinase in the regulation of KIF17 and NR2B trafficking in the animal model of chronic inflammatory pain. Tozasertib (10, 20, and 40 mg/kg i.p.), a pan aurora kinase inhibitor, significantly attenuates acute inflammatory pain and suppresses enhanced pain hypersensitivity to heat, cold, and mechanical stimuli in CFA-injected rats. Molecular investigations suggest enhanced expression of KIF17/mLin10/NR2B in L4-L5 dorsal root ganglion (DRG) and spinal cord of CFA-injected rats which was significantly attenuated on treatment with tozasertib. Moreover, tozasertib treatment significantly attenuated CFA-induced oxido-nitrosative stress and macrophage activation in DRG and microglia activation in spinal cord of rats. Findings from the current study suggest that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling.

Schizophrenia (SZ) is a severe progressive neurodegenerative as well as disruptive behavior disorder affecting innumerable people throughout the world. The discovery of potential biomarkers in the clinical scenario would lead to the development of effective methods of diagnosis and would provide an understanding of the prognosis of the disease. Moreover, breakthrough inventions for the treatment and prevention of this mysterious disease could evolve as a result of a thorough understanding of the clinical biomarkers. In this review, we have discussed about specific biomarkers of SZ an emphasis has been laid to delineate (1) diagnostic biomarkers like neuroimmune biomarkers, metabolic biomarkers, oligodendrocyte biomarkers and biomarkers of negative and cognitive symptoms, (2) therapeutic biomarkers like various neurotransmitter systems and (3) prognostic biomarkers. All the biomarkers were evaluated in drug-naïve (at least for 4 weeks) patients in order to achieve a clear comparison between schizophrenic patients and healthy controls. Also, an attempt has been made to elucidate the potential genes which serve as predictors and tools for the determination of biomarkers and would ultimately help in the prevention and treatment of this deadly illness.

Neurodegenerative disorders are threatening mankind with significant health and economic burden. Neurodegeneration involves the deterioration of neurons in the central nervous system (CNS), resulting in decreased neuronal survival. Therefore, it is of utmost requirement to develop a promising pharmacological strategy to minimize or prevent the progression of the underlying disease pathogenesis. In neurodegenerative disease conditions, neurons and glial cells present in the specific brain regions are damaged and depraved, resulting in specified disease symptoms in the patients. Neuroinflammation plays a major role in the degeneration of neuronal cells by regulating the expression of interleukin-1 beta (IL-1β), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokines Cxcl3 (C-C motif) ligand 2 (CCL2), CXCL5, granulocyte-macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), impaired tuning of immune cells and nuclear factor kappa-B (NF-κB). Considering this, it is very important to understand the in-depth role of neuroinflammation in the initiation and progression of various neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), as well as Multiple Sclerosis (MS). Recent shreds of evidence have suggested that using exogenous ligands to approach various biological molecules or cellular functioning that modulates the neuroinflammation, such as microglia response, P2X7 receptors, TLR receptors, oxidative stress, PPARγ, NF-κB signaling pathway, NLRP3 inflammasome, caspase-1 signaling pathway, and mitochondrial dysfunction, helps to combat neurodegeneration in a variety of diseases. Thus, targeting the neuroinflammatory drive could provide a beacon for the management of neurodegenerative diseases. Here, we have attempted to provide comprehensive literature suggesting the role of neuroinflammation in neurodegeneration and its implication in the development of near-future neurotherapeutics.

Cancer is an unprecedented proliferation of cells leading to abnormalities in differentiation and maturation. Treatment of primary and metastatic cancer is challenging. In addition to surgery, chemotherapy and radiation therapies have been conventionally used; however, they suffer from severe toxicity and non-specificity. Immunotherapy, the science of programming the body's own defense system against cancer has gained tremendous attention in the last few decades. However, partial immunogenic stimulation, premature degradation and inability to activate dendritic and helper T cells has resulted in limited clinical success. The era of nanomedicine has brought about several breakthroughs in various pharmaceutical and biomedical fields. Hereby, we review and discuss the interplay of tumor microenvironment (TME) and the immunological cascade and how they can be employed to develop nanoparticle-based cancer vaccines and immunotherapies. Nanoparticles composed of lipids, polymers and inorganic materials contain useful properties suitable for vaccine development. Proteinaceous vaccines derived from mammalian viruses, bacteriophages and plant viruses also have unique advantages due to their immunomodulation capabilities. This review accounts for all such considerations. Additionally, we explore how attributes of nanotechnology can be utilized to develop successful nanomedicine-based vaccines for cancer therapy. This article is categorized under: Nanotechnology Approaches to BiologyNanoscale Systems in Biology Therapeutic Approaches and Drug DiscoveryNanomedicine for Oncologic Disease.

The neurodegeneration and its related CNS pathologies need an urgent toolbox to minimize the global mental health burden. The neuroimmune system critically regulates the brain maturation and survival of neurons across the nervous system. The chronic manipulated immunological drive can accelerate the neuronal pathology hence promoting the burden of neurodegenerative disorders. The gut is home for trillions of microorganisms having a mutual relationship with the host system. The gut-brain axis is a unique biochemical pathway through which the gut residing microbes connects with the brain cells and regulates various physiological and pathological cascades. The gut microbiota and CNS communicate using a common language that synchronizes the tuning of immune cells. The intestinal gut microbial community has a profound role in the maturation of the immune system as well as the development of the nervous system. We have critically summarised the clinical and preclinical reports from the past a decade emphasising that the significant changes in gut microbiota can enhance the host susceptibility towards neurodegenerative disorders. In this review, we have discussed how the gut microbiota-mediated immune response inclines the host physiology towards neurodegeneration and indicated the gut microbiota as a potential future candidate for the management of neurodegenerative disorders.

Parkinson’s disease (PD) is the second most common neurodegenerative illness majorly affecting the population between the ages of 55 to 65 years. Progressive dopaminergic neuronal loss and the collective assemblage of misfolded alpha-synuclein in the substantia nigra, remain notable neuro-pathological hallmarks of the disease. Multitudes of mechanistic pathways have been proposed in attempts to unravel the pathogenesis of PD but still, it remains elusive. The convergence of PD pathology is found in organelle dysfunction where mitochondria remain a major contributor. Mitochondrial processes like bioenergetics, mitochondrial dynamics, and mitophagy are under strict regulation by the mitochondrial genome and nuclear genome. These processes aggravate neurodegenerative activities upon alteration through neuroinflammation, oxidative damage, apoptosis, and proteostatic stress. Therefore, the mitochondria have grabbed a central position in the patho-mechanistic exploration of neurodegenerative diseases like PD. The management of PD remains a challenge to physicians to date, due to the variable therapeutic response of patients and the limitation of conventional chemical agents which only offer symptomatic relief with minimal to no disease-modifying effect. This review describes the patho-mechanistic pathways involved in PD not only limited to protein dyshomeostasis and oxidative stress, but explicit attention has been drawn to exploring mechanisms like organelle dysfunction, primarily mitochondria and mitochondrial genome influence, while delineating the newer exploratory targets such as GBA1, GLP, LRRK2, and miRNAs and therapeutic agents targeting them.

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as an interacting protein partner of full-length and C-terminal (Pro1010-Cys1493) CSB in two independent screens. LEO1 is a member of the RNA polymerase associated factor 1 complex (PAF1C) with roles in transcription elongation and chromatin modification. Supportive of the Y2H results, purified, recombinant LEO1 and CSB directly interact in vitro, and the two proteins exist in a common complex within human cells. In addition, fluorescently tagged LEO1 and CSB are both recruited to localized DNA damage sites in human cells. Cell fractionation experiments revealed a transcription-dependent, coordinated association of LEO1 and CSB to chromatin following either UVC irradiation or cisplatin treatment of HEK293T cells, whereas the response to menadione was distinct, suggesting that this collaboration occurs mainly in the context of bulky transcription-blocking lesions. Consistent with a coordinated interaction in DNA repair, LEO1 knockdown or knockout resulted in reduced CSB recruitment to chromatin, increased sensitivity to UVC light and cisplatin damage, and reduced RNA synthesis recovery and slower excision of cyclobutane pyrimidine dimers following UVC irradiation; the absence of CSB resulted in diminished LEO1 recruitment. Our data indicate a reciprocal communication between CSB and LEO1 in the context of transcription-associated DNA repair and RNA transcription recovery.

Traditional Indian medical practices (Ayurveda, Siddha, Unani, and homeopathy) are a vast reservoir of knowledge about medicinal plants. The promising pharmacological properties of these plants have paved the way for developing therapy against novel Coronavirus (CoV) infection. The current review will summarize published works of literature on the effects of traditional Indian medicinal plants against acute respiratory infection (COVID-19, SARS, Influenza, and Respiratory syncytial virus infection) and registered clinical trials of traditional Indian herbal medicines in COVID-19. The current study aims to comprehensively evaluate the data of traditional Indian medicinal plants to warrant their use in COVID-19 management. PubMed, Embase, and Cochrane databases were searched along with different clinical trial databases. A total of 22 relevant traditional Indian medicinal plants (35 relevant studies) were included in the current study having potential antiviral properties against virus-induced respiratory illness along with promising immunomodulatory and thrombolytic properties. Further, 36 randomized and nonrandomized registered clinical trials were also included that were aimed at evaluating the efficacy of herbal plants or their formulations in COVID-19 management. The antiviral, immunomodulatory, and thrombolytic activities of the traditional Indian medicinal plants laid down a strong rationale for their use in developing therapies against SARS-CoV-2 infection. The study identified some important potential traditional Indian medicinal herbs such as Ocimum tenuiflorum, Tinospora cordifolia, Achyranthes bidentata, Cinnamomum cassia, Cydonia oblonga, Embelin ribes, Justicia adhatoda, Momordica charantia, Withania somnifera, Zingiber officinale, Camphor, and Kabusura kudineer, which could be used in therapeutic strategies against SARS-CoV-2 infection.

Kinesins are the motor proteins that transport excitatory receptors to the synaptic membrane by forming a complex with receptor cargo leading to central sensitization causing neuropathic pain. Many regulatory proteins govern the transit of receptors by activating kinesin, and Aurora kinases are one of them. In this study, we have performed in silico molecular dynamics simulation to delineate the dynamic interaction of Aurora kinase A with its pharmacological inhibitor, tozasertib. The results from the molecular dynamics study shows that tozasertib-Aurora kinase A complex is stabilized through hydrogen bonding, polar interactions, and water bridges. Findings from the in vitro studies suggest that tozasertib treatment significantly attenuates lipopolysaccharide (LPS)-induced increase in oxidonitrosative stress and kif11 overexpression in C6 glial cell lines. Further, we investigated the regulation of kif11 and its modulation by tozasertib in an animal model of neuropathic pain. Two weeks post-CCI surgery we observed a significant increase in pain hypersensitivity and kif11 overexpression in DRG and spinal cord of nerve-injured rats. Tozasertib treatment significantly attenuates enhanced pain hypersensitivity along with the restoration of kif11 expression in DRG and spinal cord and oxidonitrosative stress in the sciatic nerve of injured rats. Our findings demonstrate the potential role of tozasertib for the management of neuropathic pain.

Human tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis (Mtb) that inhabits inside and amidst immune cells of the host with adapted physiology to regulate interdependent cellular functions with intact pathogenic potential. The complexity of this disease is attributed to various factors such as the reactivation of latent TB form after prolonged persistence, disease progression specifically in immunocompromised patients, advent of multi- and extensivelydrug resistant (MDR and XDR) Mtb strains, adverse effects of tailor-made regimens, and drug-drug interactions among anti-TB drugs and anti-HIV therapies. Thus, there is a compelling demand for newer anti-TB drugs or regimens to overcome these obstacles. Considerable multifaceted transformations in the current TB methodologies and molecular interventions underpinning hostpathogen interactions and drug resistance mechanisms may assist to overcome the emerging drug resistance. Evidently, recent scientific and clinical advances have revolutionised the diagnosis, prevention, and treatment of all forms of the disease. This review sheds light on the current understanding of the pathogenesis of TB disease, molecular mechanisms of drug-resistance, progress on the development of novel or repurposed anti-TB drugs and regimens, host-directed therapies, with particular emphasis on underlying knowledge gaps and prospective for futuristic TB control programs.

Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are promising targets for neuropathic pain and other CNS disorders. Based on our previous lead compound SIH 3, we designed and synthesized a series of 4-methylsulfonylphenyl semicarbazones and evaluated for FAAH and MAGL inhibition properties. Most of the compounds showed potency towards both enzymes with leading FAAH selectivity. Compound (Z)-2-(2,6-dichlorobenzylidene)-N-(4-(methylsulfonyl)phenyl)hydrazine-1-carboxamide emerged as the lead inhibitor against both FAAH (IC

Kinesins (KIF's) are the motor proteins which are recently reported to be involved in the trafficking of nociceptors leading to chronic pain. Aurora kinases are known to be involved in the regulation of KIF proteins which are associated with the activation of N-methyl-D-aspartate (NMDA) receptors. Here, we investigated the effect of tozasertib, a pan-Aurora kinase inhibitor, on nerve injury-induced evoked and chronic ongoing pain in rats and the involvement of kinesin family member 17 (KIF17) and NMDA receptor subtype 2B (NR2B) crosstalk in the same. Rats with chronic constriction injury showed a significantly decreased pain threshold in a battery of pain behavioural assays. We found that tozasertib [10, 20, and 40 mg/kg intraperitoneally (i.p.)] treatment showed a significant and dose-dependent inhibition of both evoked and chronic ongoing pain in rats with nerve injury. Tozasertib (40 mg/kg i.p.) and gabapentin (30 mg/kg i.p.) treatment significantly inhibits spontaneous ongoing pain in nerve injured rats but did not produce any place preference behaviour in healthy naïve rats pointing towards their non-addictive analgesic potential. Moreover, tozasertib (10, 20, and 40 mg/kg i.p.) and gabapentin (30 mg/kg i.p.) treatment did not altered the normal pain threshold in healthy naïve rats and didn't produce central nervous system associated side effects as well. Western blotting and reverse transcription polymerase chain reaction studies suggested enhanced expressions of NR2B and KIF-17 along with increased nuclear factor kappa β (NFkβ), tumour necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) levels in dorsal root ganglion (DRG) and spinal cord of nerve injured rats which was significantly attenuated on treatment with different does of Tozasertib. Findings from the current study suggests that inhibition of pan-Aurora kinase decreased KIF-17 mediated NR2B activation which further leads to significant inhibition of evoked and chronic ongoing pain in nerve-injured rats.

Aptamer-based proteomics revealed differentially abundant proteins in Alzheimer’s disease (AD) brains in the Baltimore Longitudinal Study of Aging and Religious Orders Study (mean age, 89 ± 9 years...

Description, Brain proteins altered in young APOE ε4 carriers are found decades later in Alzheimer’s disease and present novel drug targets., Aptamer-based proteomics revealed differentially abundant proteins in Alzheimer’s disease (AD) brains in the Baltimore Longitudinal Study of Aging and Religious Orders Study (mean age, 89 ± 9 years). A subset of these proteins was also differentially abundant in the brains of young APOE ε4 carriers relative to noncarriers (mean age, 39 ± 6 years). Several of these proteins represent targets of approved and experimental drugs for other indications and were validated using orthogonal methods in independent human brain tissue samples as well as in transgenic AD models. Using cell culture–based phenotypic assays, we showed that drugs targeting the cytokine transducer STAT3 and the Src family tyrosine kinases, YES1 and FYN, rescued molecular phenotypes relevant to AD pathogenesis. Our findings may accelerate the development of effective interventions targeting the earliest molecular triggers of AD.

Neuropathic pain is due to an injury or disease of the somatosensory nervous system, which accounts for a significant economical and health burden to society. Due to poor understanding of their underlying mechanisms, the available treatments merely provide symptomatic relief and precipitates a variety of adverse effects. This suggests that there is an unmet medical need that must be addressed with effective strategies for the development of novel therapeutics. Sphingosine kinase 2 (SphK2) is an oncogenic lipid kinase that has emerged as a promising target for chronic pain and other diseases. In the present study, we have explored the structure-based virtual high-throughput screening of the Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBE) to identify potent natural products as inhibitors of SphK2. A molecular docking study was performed to calculate binding affinities and specificity to identify potential leads against SphK2. Initially, hits were selected by the implementation of absorption, distribution, metabolism, excretion and toxicity properties, Lipinski rule, and PAINS filters. The top-scoring hits also exhibiting an optimal ADMET profile were subjected to MM/GBSA free binding free energy calculation and molecular dynamics simulation. The results from molecular dynamics simulation revealed a stable ligand -SphK2 complex with protein and ligand RMSD within reasonable limits. Overall, we identified compounds, NuBBE_972 and NuBBE_1107 as potential inhibitors of SphK2 with optimal pharmacokinetic properties which have the potential to be developed as novel therapeutics for the management of chronic pain.Communicated by Ramaswamy H. Sarma.

Neuropathic pain (NeP) is a complex chronic pain condition associated with nerve injury. Approximately, 7-10% of the general population across the globe is suffering from this traumatic condition, but the existing treatment strategies are inadequate to deliver pain relief and are associated with severe adverse effects. To overcome these limitations, lot of research is focussed on developing new molecules with high potency and fewer side effects, novel cell and gene-based therapies and modification of the previously approved drugs by different formulation aspects. Nanomedicine has attracted a lot of attention in the treatment of many diverse pathological conditions because of their unique physiochemical and biological properties. In this manuscript, we highlighted the emerging role of nanomedicine in different therapies (drug, cell and gene), also we emphasised on the challenges associated with nanomedicine such as development of well-characterised nanoformulation, scaling of batches with reproducible results and toxicity along with this we discussed about the future of nanomedicine in the treatment of neuropathic pain.

RhoA/Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) has appeared as a potential therapeutic target in numerous diseases, because of its preventing action on various enzymes providing antioxidant and cytoprotective action. Progression and pathophysiology of diabetic nephropathy have also shown potential involvement of oxidative stress and inflammatory pathways. In the present study, we investigated the effect of kaempferol on hyperglycemia-induced activation of RhoA kinase and associated inflammatory signaling cascade. Currently there is only small literature available on the mechanism of anti-diabetic and nephroprotective action of this compound, which creates a void. Therefore, we focused here on the investigation of molecular mechanisms for kaempferol by means of in vitro testing, using rat (NRK-52E) and human renal tubular epithelial cells (RPTEC). Our findings suggest that kaempferol inhibits hyperglycemia-induced activation of RhoA and decreased oxidative stress, pro-inflammatory cytokines (TNF-α and IL-1β) and fibrosis (TGF-β1 expression, extracellular matrix protein expression) in NRK-52E and RPTEC cells. Therefore, kaempferol can be used as a potential therapeutic for the treatment of diabetic nephropathy.

Alcohol consumption for a longer period of time is linked with neuronal damage and an increase in inflammatory signaling resulting in cell death and dementia. Natural compounds are the focus of research due to their high efficacy and good safety profile. Here we have investigated the effect of chronic epigallocatechin-3-gallate (EGCG) administration against the alcohol-induced cognitive deficit rats. Male Wistar rats were exposed to the ethanol (10 g/kg; oral gavage) for ten weeks and treated with EGCG (25, 50, and 100 mg/kg) for the same duration. Ethanol exposure led to the impaired spatial memory and learning in rats assessed using the Morris water maze and elevated plus-maze test. Further, we assessed the role of EGCG in mitigating the oxidative stress, neuroinflammatory and cell death signaling associated markers. Co-administration with EGCG significantly prevented all the behavioral, biochemical and molecular alterations in the different brain regions of ethanol-treated rats in a dose-dependent manner. EGCG suppressed the acetylcholinesterase activity, increased oxidative–nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in both the cortex and hippocampus of ethanol-treated rats. Our preliminary study demonstrated that EGCG improves the oxido-nitrosative stress, inflammation, and cell death signaling associated with ethanol-induced cognitive dysfunction. This suggests the potential role of EGCG in mitigating the cognitive deficits associated with chronic alcohol consumption.

Alcohol consumption for a longer period of time is linked with neuronal damage and an increase in inflammatory signaling resulting in cell death and dementia. Natural compounds are the focus of research due to their high efficacy and good safety profile. Here we have investigated the effect of chronic epigallocatechin-3-gallate (EGCG) administration against the alcohol-induced cognitive deficit rats. Male Wistar rats were exposed to the 12% ethanol (10 g/kg; oral gavage) for ten weeks and treated with EGCG (25, 50, and 100 mg/kg) for the same duration. Ethanol exposure led to the impaired spatial memory and learning in rats assessed using the Morris water maze and elevated plus-maze test. Further, we assessed the role of EGCG in mitigating the oxidative stress, neuroinflammatory and cell death signaling associated markers. Co-administration with EGCG significantly prevented all the behavioral, biochemical and molecular alterations in the different brain regions of ethanol-treated rats in a dose-dependent manner. EGCG suppressed the acetylcholinesterase activity, increased oxidative–nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in both the cortex and hippocampus of ethanol-treated rats. Our preliminary study demonstrated that EGCG improves the oxido-nitrosative stress, inflammation, and cell death signaling associated with ethanol-induced cognitive dysfunction. This suggests the potential role of EGCG in mitigating the cognitive deficits associated with chronic alcohol consumption.

Cockayne syndrome (CS) is a segmental premature aging syndrome caused primarily by defects in the CSA or CSB genes. In addition to premature aging, CS patients typically exhibit microcephaly, progressive mental and sensorial retardation and cutaneous photosensitivity. Defects in the CSB gene were initially thought to primarily impair transcription-coupled nucleotide excision repair (TC-NER), predicting a relatively consistent phenotype among CS patients. In contrast, the phenotypes of CS patients are pleiotropic and variable. The latter is consistent with recent work that implicates CSB in multiple cellular systems and pathways, including DNA base excision repair, interstrand cross-link repair, transcription, chromatin remodeling, RNAPII processing, nucleolin regulation, rDNA transcription, redox homeostasis, and mitochondrial function. The discovery of additional functions for CSB could potentially explain the many clinical phenotypes of CSB patients. This review focuses on the diverse roles played by CSB in cellular pathways that enhance genome stability, providing insight into the molecular features of this complex premature aging disease.

India being the second largest wheat producer in the world provides 13% of global wheat supply. Traditional breeding approaches are limited by the low genetic variability, complexity of stress tolerance traits and yield components and the lack of efficient selection techniques under stress conditions. Although the physiological tolerance indices are not directly related to yield but their use might prove increasingly useful. Integration of physiological traits complimented with efficient breeding methodologies will drive the present research to the required wheat yields. A set of twelve wheat lines were used to study the effect of different physiological parameters on the overall yield and its component traits. Progressive increase in NDVI values was noticed during the vegetative phase and a definite decline in values was observed during milk development to ripening stages in the genotypes. In high yielding genotypes a sharp decline of NDVI values was observed from anthesis to milk development stage. This set of genotypes generally showed a slower increase in NDVI values from seedling growth stage to inflorescence emergence stage and faster decline from inflorescence stage to ripening stage. The grain filling occurs in high temperatures and genotypes showing faster utilization of green matter showed higher yield.

COVID-19 pandemic has created a healthcare crisis across the world and has put human life under life-threatening circumstances. The recent discovery of the crystallized structure of the main protease (Mpro) from SARS-CoV-2 has provided an opportunity for utilizing computational tools as an effective method for drug discovery. Targeting viral replication has remained an effective strategy for drug development. Mpro of SARS-COV-2 is the key protein in viral replication as it is involved in the processing of polyproteins to various structural and nonstructural proteins. Thus, Mpro represents a key target for the inhibition of viral replication specifically for SARS-CoV-2. We have used a virtual screening strategy by targeting Mpro against a library of commercially available compounds to identify potential inhibitors. After initial identification of hits by molecular docking-based virtual screening further MM/GBSA, predictive ADME analysis, and molecular dynamics simulation were performed. The virtual screening resulted in the identification of twenty-five top scoring structurally diverse hits that have free energy of binding (ΔG) values in the range of −26-06 (for compound AO-854/10413043) to −59.81 Kcal/mol (for compound 329/06315047). Moreover, the top-scoring hits have favorable AMDE properties as calculated using in silico algorithms. Additionally, the molecular dynamics simulation revealed the stable nature of protein-ligand interaction and provided information about the amino acid residues involved in binding. Overall, this study led to the identification of potential SARS-CoV-2 Mpro hit compounds with favorable pharmacokinetic properties. We believe that the outcome of this study can help to develop novel Mpro inhibitors to tackle this pandemic. Communicated by Ramaswamy H. Sarma

Natural products and leads inspired by them have acted as a probe for successful drug discovery for many decades. Pain is an obnoxious sensory and emotional experience associated with potential tissue damage. It affects the quality of life of patients to a greater extent. Despite the availability of several agents targeting TRP receptors, none of them can proficiently alleviate neuropathic pain. TRPV1 is a prospective target for treating neuropathic pain as it is recognized to modulate the pain circuitry at the periphery and the central level. In this review, we have discussed several natural molecules, such as Capsaicinoids, Capsinoids, Piperine, Eugenol, Scutigeral, Ginsenosides, Cinnamaldehyde, Camphor, Shogaol, Gingerols, Zingerone, Allicin, Evodiamine, Allylisothiocyanate, Cannabidiol, Ricinoleic acid, Isovelleral, Capsazepine, Thapsigargin, Pellitorine, Yohimbine, Curcumin and some semi-synthetic analogues that activate TRPV1 channels and consequently, can be further harnessed for the treatment of neuropathic pain.