HC070, a Transient Receptor Potential Canonical 5 (TRPC5) Channels Inhibitor Ameliorated α-synuclein Preformed Fibrils-Induced Parkinson's Disease: A Neurobehavioural and Mechanistic Study.

Alpha-synuclein pathology is a characteristic feature of Parkinson's disease (PD) and related synucleinopathies. As a result, reducing alpha-synuclein pathology is one of the mechanisms being looked at for the development of newer agents which target these diseases. In the present study, we investigated the potential of HC070, a transient receptor potential canonical 5 (TRPC5) channel inhibitor in reducing alpha-synuclein pathology in PD.

Decoding the Nectin Interactome: Implications for Brain Development, Plasticity, and Neurological Disorders.

The nectin family of cell adhesion molecules (CAMs) comprising nectins and nectin-like molecules has emerged as a key regulator of various pivotal neural processes, including neuronal development, migration, synapse formation, and plasticity. Nectins engage in homophilic and heterophilic interactions to mediate cell-cell adhesion, contributing to the establishment and maintenance of neural circuits. Their extracellular domains facilitate trans-synaptic interactions, while intracellular domains participate in signaling cascades influencing cytoskeletal dynamics and synaptic function.

Insights into early generation synthetic amphidiploid : a strategy to harness maximum parental genomic diversity for improving Indian mustard.

In India, amphidiploid (AABB, 2n=36) is a significant oilseed crop, but its small gene pool limits its ability to develop traits of higher breeding and economic value. Through interspecific hybridization from various lines of the progenitor species, resynthesized (RBJ) can provide breeders with additional resources for creating genetically diverse stress-tolerant and high-yielding cultivars. Three accessions and eight accessions were crossed in this study to develop 33 synthetic lines.

Bispecific domain antibody attenuates airway hyperresponsiveness and pulmonary inflammation in ovalbumin-lipopolysaccharide induced asthma model by inhibiting IL-23 and TNF-α.

Asthma, a chronic multi-factorial pulmonary inflammatory condition with a high morbidity rate, is characterized by airway hyperresponsiveness and persistent pulmonary inflammation. There is a need to develop more effective treatment(s) for the management of asthma. In this study, we have investigated the therapeutic potential of BiSpekDAb (an engineered bispecific antibody comprising an anti-IL-23 domain antibody and an anti-TNF-α domain antibody fused together via flexible linkers to a half-life extension partner) in asthma.

Neuroprotective potential of ApoE-mimetic peptide (ApoEFrag) in stroke models: Neurobehavioural and mechanistic study.

Stroke is the second leading cause of death worldwide, and currently, there is no effective neuroprotective agent available for its treatment. Though apolipoprotein E (ApoE) showed potential as a neuroprotective agent for CNS disorders, however, its large size limits its clinical application. To overcome this issue, smaller ApoE-mimetic peptides that mimic the biological functions of ApoE have been developed.

Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.

Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis.

Characterization of neuronal oscillations in the prelimbic cortex, nucleus accumbens and CA1 hippocampus during object retrieval task in rats predisposed to early life stress.

Background: Early life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heightened curiosity and associated risk-taking behavior in the object retrieval task (ORT). However, the neural correlates of curiosity in adolescent rats predisposed to early life stress remain unexplored.

High sensitivity direct magnetic field detection based metrology for ultra-thin magnetic films and Li-ion cells.

Ultra-low magnetic field sensing is emerging as a tool for materials' diagnostics, particularly for the operando studies of electrochemical systems. A magnetic metrology system having the capability of sensing fields as low as ∼1.88 pT has been setup for such studies using a commercial atomic magnetometer.

RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.

Neuropathic pain (NP) is one of the debilitating pain phenotypes that leads to the progressive degeneration of the central as well as peripheral nervous system. NP is often associated with hyperalgesia, allodynia, paresthesia, tingling, and burning sensations leading to disability, motor dysfunction, and compromised psychological state of the patients. Most of the conventional pharmacological agents are unable to improve the devastating conditions of pain because of their limited efficacy, undesirable side effects, and multifaceted pathophysiology of the diseased condition.

Organophosphate pesticide chlorpyrifos and its metabolite 3,5,6-trichloropyridinol downregulate the expression of genes essential for spermatogenesis in caprine testes.

Organophosphate pesticides have potent endocrine disrupting effects, hence banned in many countries. However, many organophosphates like chlorpyrifos, malathion et cetera continue to be used in some countries (Wołejko et al., 2022; Wołejko et al.

Transient receptor potential channels as an emerging target for the treatment of Alzheimer's disease: Unravelling the potential of pharmacological interventions.

Alzheimer's disease (AD) is a devastating disorder with a multifaceted aetiology characterized by dementia, which later progresses to cognitive impairment. Significant efforts have been made to develop pharmacological interventions that slow down the pathogenesis of AD. However, conventional drugs have failed to satisfactorily treat AD and are more focussed towards symptomatic management.

Pharmacological agents targeting transient receptor potential (TRP) channels in neuropathic pain: Preclinical and clinical status.

Neuropathic pain generally affects 7-10% population worldwide and an estimated ∼1 in every 20 individuals in western countries suffer and burden to society. The most limiting factor with existing therapies includes dose escalation issues, off-target side effects and poor translation of randomized trials into clinical practice. Neuropathic pain is a broad term that comprises direct injury/damage to the central and/or peripheral nervous system, leads to maladaptive changes in neuronal as well as in non-neuronal cells, which further contributes to the spontaneous pain, sensory and motor deficit along with altered sensitivity towards the noxious as well as non-noxious stimulus.

Study of defect density of copper vacancies in chalcogenide CuSbS, CuSbSe, CuBiS, and CuBiSe heterojunction thin-film solar cells.

In the past decade, a new family of ternary chalcogenide absorber (TCA) materials MMX (where M = Cu, Ag, Pb; M = Sb, Bi, In; and X = S, Se, Te) have been studied. The copper family of ternary chalcogenide CuSbS CuSbSe CuBiS, and CuBiSe is an amazing absorber material for thin-film solar cells because of their suitable band gap, high absorption coefficient and inexpensive, nontoxic, environment friendly and sustainable nature. In the presented work, first time simulated defect density of copper vacancies in CuSbS (CAS), CuSbSe (CASe), CuBiS (CBS) and CuBiSe (CBSe) has based heterojunction thin-film solar cells (HJTFSCs) with buffer CdS, intrinsic i-ZnO, window ZnO: Al and back contact Mo and set the cell scheming ZnO: Al/i-ZnO/n-CdS/p-TCA/Mo using SCAPS 1D.

Compound 3K attenuates isoproterenol-induced cardiac hypertrophy by inhibiting pyruvate kinase M2 (PKM2) pathway.

Aim: Chronic sympathetic stimulation has been identified as a primary factor in the pathogenesis of cardiac hypertrophy (CH). However, there is no appropriate treatment available for the management of CH. Recently, it has been revealed that pyruvate kinase M2 (PKM2) plays a significant role in cardiac remodeling, fibrosis, and hypertrophy.

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness.

Finger millet (Eleusine coracana) enhancement through genomic resources and breeding methods: current implications and potential future interventions.

Finger millet (Eleusine coracana) is an essential staple crop in many regions of Africa and Asia, valued for its nutritional content and resilience in challenging agro-ecological conditions. The enhancement of finger millet through genomic resources and breeding methods represents a promising avenue for addressing food and nutritional security. Current efforts in this field have harnessed genomic technologies to decipher the crop's genetic diversity and identify key traits related to yield, disease resistance, and nutritional content.

Changing etiological spectrum of acute liver failure.

Background And Objectives: Acute liver failure (ALF) is an uncommon but potentially dramatic syndrome characterized by massive hepatic necrosis and has a very high mortality rate of 50% to 75% without liver transplantation. This study is aimed at analyzing the etiological spectrum of ALF patients and compare these with ALF mimics such as malaria, dengue fever and other tropical infectious diseases.

Methods: The study population included patients who presented with ALF and ALF mimics in a tertiary care center over two years.

Cardioprotective potential of compound 3K, a selective PKM2 inhibitor in isoproterenol-induced acute myocardial infarction: A mechanistic study.

Myocardial infarction (MI) or heart attack arises from acute or chronic prolonged ischemic conditions in the myocardium. Although several risk factors are associated with MI pathophysiology, one of the risk factors is an imbalance in the oxygen supply. The current available MI therapies are still inadequate due to the complexity of MI pathophysiology.

Ion Channels and Metal Ions in Parkinson's Disease: Historical Perspective to the Current Scenario.

Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive.

Text-Mining and Video Analytics of COVID-19 Narratives Shared by Patients on YouTube.

This study explores how individuals who have experienced COVID-19 share their stories on YouTube, focusing on the nature of information disclosure, public engagement, and emotional impact pertaining to consumer health. Using a dataset of 186 YouTube videos, we used text mining and video analytics techniques to analyze textual transcripts and visual frames to identify themes, emotions, and their relationship with viewer engagement metrics. Findings reveal eight key themes: infection origins, symptoms, treatment, mental well-being, isolation, prevention, government directives, and vaccination.

Scrub Typhus: An Acute Precipitant for Acute on Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high mortality. Many acute precipitating factors have been implicated in triggering the acute event of ACLF, with bacterial infections being a common precipitant. However, many other precipitants can cause ACLF; therefore, identification of these factors early in the golden window and their treatment can result in improved prognosis.

Supplementation of probiotic Bifidobacterium breve Bif11 reverses neurobehavioural deficits, inflammatory changes and oxidative stress in Parkinson's disease model.

Human gut microbiota are thought to affect different physiological processes in the body, including brain functions. Gut dysbiosis has been linked to the progression of Parkinson's disease (PD) and thus, restoring the healthy gut microbiota with supplementation of putative probiotic strains can confer some benefits in PD. In the current study, we explored the neuroprotective potential of Bifidobacterium breve Bif11 supplementation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated female Sprague Dawley rats.

An insight into crosstalk among multiple signalling pathways contributing to the pathophysiology of PTSD and depressive disorders.

Post-traumatic stress disorder (PTSD) and depressive disorders represent two significant mental health challenges with substantial global prevalence. These are debilitating conditions characterized by persistent, often comorbid, symptoms that severely impact an individual's quality of life. Both PTSD and depressive disorders are often precipitated by exposure to traumatic events or chronic stress.