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.

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.

Piezoelectricity in chalcogenide perovskites.

Piezoelectric materials show potential to harvest the ubiquitous, abundant, and renewable energy associated with mechanical vibrations. However, the best performing piezoelectric materials typically contain lead which is a carcinogen. Such lead-containing materials are hazardous and are being increasingly curtailed by environmental regulations.

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.

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.

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.

Effect of patient and diagnostic intervals on the risk of advanced stage in Indian patients with seven types of gastrointestinal cancers: A retrospective cohort study.

Objectives: Advanced stage is linked to prolonged patient and diagnostic interval for gastrointestinal (GI) cancers. However, objective evidence of this fact is not so forthcoming. Our aim was to study the effect of these intervals on the risk of advanced stage for GI cancers.

Engineered polyspecific antibodies: A new frontier in the field of immunotherapeutics.

The 21st-century beginning remarked with the huge success of monospecific MAbs, however, in the last couple of years, polyspecific MAbs (PsAbs) have been an interesting topic and show promise of being biobetter than monospecific MAbs. Polyspecificity, in which a single antibody serves multiple specific target binding, has been hypothesized to contribute to the development of a highly effective antibody repertoire for immune defence. This polyspecific MAb trend represents an explosion that is gripping the whole pharmaceutical industry.

Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status.

Angiogenesis is the physiological process that results in the formation of new blood vessels develop from pre-existing vasculature and plays a significant role in several physiological and pathological processes. Inhibiting angiogenesis, a crucial mechanism in the growth and metastasis of cancer, has been proposed as a potential anticancer therapy. Different studies showed the beneficial effects of angiogenesis inhibitors either in patients suffering from different cancers, alone or in combination with conventional therapies.

BTD: A TRPC5 activator ameliorates mechanical allodynia in diabetic peripheral neuropathic rats by modulating TRPC5-CAMKII-ERK pathway.

Mechanical allodynia is a serious complication of painful diabetic neuropathy (PDN) with limited treatment options. The transient receptor potential canonical 5 (TRPC5) channel is a promising target in pain; however, its role in painful diabetic neuropathy has not yet been elucidated. In this study, we have investigated the role of TRPC5 channels using BTD [N-{3-(adamantan-2-yloxy)-propyl}-3-(6-methyl-1,1-dioxo-2H-1λ,2,4-benzothiadiazin-3-yl)-propanamide)],a potent TRPC5 activator and HC070, as TRPC5 channel inhibitor in rat model of PDN.

Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.

Myocardial infarction (MI) is a major cause of mortality and disability globally. MI results from acute or chronic myocardial ischemia characterized by an imbalance of oxygen demand and supply, leading to irreversible myocardial injury. Despite several significant efforts in the understanding of MI, the therapy of MI is not satisfactory due to its complicated pathophysiology.

Amelioration of Parkinson's disease by pharmacological inhibition and knockdown of redox sensitive TRPC5 channels: Focus on mitochondrial health.

Aims: Transient receptor potential canonical 5 (TRPC5) channels are redox-sensitive cation-permeable channels involved in temperature and mechanical sensation. Increased expression and over-activation of these channels has been implicated in several central nervous system disorders such as epilepsy, depression, traumatic brain injury, anxiety, Huntington's disease and stroke. TRPC5 channel activation causes increased calcium influx which in turn activates numerous downstream signalling pathways involved in the pathophysiology of neurological disorders.

Aetiology and clinical spectrum of gastric outlet obstruction in North West India.

Our study to evaluate the aetiological and clinical spectrum of gastric outlet obstruction (GOO) in North-west India showed malignant cause (54.9%) was more common than benign (45.1%).