Publications by authors named "Puneet Randhawa"

Background: Sepsis causes multiple organ dysfunctions and raises mortality and morbidity rates through a dysregulated host response to infection. Despite the growing research interest over the last few years, no satisfactory treatment exists. Naringin, a naturally occurring bioflavonoid with vast therapeutic potential in citrus fruits and Chinese herbs, has received much attention for treating sepsis-associated multiple organ dysfunctions.

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Depression is the most common mental health disorder worldwide; however, the exact cellular and molecular mechanisms of this major depressive disorder are unclear so far. Experimental studies have demonstrated that depression is associated with significant cognitive impairment, dendrite spine loss, and reduction in connectivity among neurons that contribute to symptoms associated with mood disorders. Rho/Rho-associated coiled-coil containing protein kinase (ROCK) receptors are exclusively expressed in the brain and Rho/ROCK signaling has gained considerable attention as it plays a crucial role in the development of neuronal architecture and structural plasticity.

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Despite clinical advances, ischemia-induced cardiac diseases remain an underlying cause of death worldwide. Epigenetic modifications, especially alterations in the acetylation of histone proteins play a pivotal role in counteracting stressful conditions, including ischemia. In our study, we found that histone active mark H3K27ac was significantly reduced and histone repressive mark H3K27me3 was significantly upregulated in the cardiomyocytes exposed to the ischemic condition.

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Cardiovascular disorder is the major health burden and cause of death among individuals worldwide. As the cardiomyocytes lack the ability for self-renewal, it is utmost necessary to surveil the protein quality in the cells. The Bcl-2 associated anthanogene protein (BAG) family and molecular chaperones (HSP70, HSP90) actively participate in maintaining cellular protein quality control (PQC) to limit cellular dysfunction in the cells.

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Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb.

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Melatonin, an emphatic endogenous molecule exerts protective effects either via activation of G-protein coupled receptors (Melatonin receptors, MTR 1-3), tumor necrosis factor receptor (TNFR), toll like receptors (TLRS), nuclear receptors (NRS) or by directly scavenging the free radicals. MTRs are extensively expressed in the heart as well as in the coronary vasculature. Accumulating evidences have indicated the existence of a strong correlation between reduction in the circulating level of melatonin and precipitation of heart attack.

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The aging process induces a plethora of changes in the body including alterations in hormonal regulation and metabolism in various organs including the heart. Aging is associated with marked increase in the vulnerability of the heart to ischemia-reperfusion injury. Furthermore, it significantly hampers the development of adaptive response to various forms of conditioning stimuli (pre/post/remote conditioning).

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Remote ischemic preconditioning (RIPC) is an innovative treatment strategy that alleviates ischemia-reperfusion injury, whereby short episodes of regional ischemia and reperfusion delivered to remote organs including hind limb, kidney and intestine, and so on provide protection to the heart. The RIPC is known to reduce infarct size, serum levels of cardiac enzymes, and myocardial dysfunction in various animal species as well as in patients. There have been a large number of studies suggesting that the ATP-sensitive potassium channels (K channel) play a significant role as a mediator or end effector in RIPC.

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Remote ischemic preconditioning (RIPC) is the phenomenon that harnesses the body's endogenous protective mechanisms against prolonged ischemia-reperfusion-induced injury. The present study aimed to explore the involvement of glycogen synthase kinase-3β and gap junction signaling in TRPV and remote hind preconditioning-induced cardioprotection. In the present study, four consecutive cycles (5min of ischemia-reperfusion) of remote hind limb preconditioning stimulus were delivered using a blood pressure cuff fastened at the inguinal level of the rat.

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Background: Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient nonlethal ischemia and reperfusion episodes confer protection against prolonged ischemia reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored.

Objective: This study aimed to inspect the putative involvement of TRPV -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection.

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Reactive oxygen species are the reactive molecules that are derived from molecular oxygen and play an important role as redox signaling molecules to confer cardioprotection. Various scientists have demonstrated the key role of redox signaling in cardioprotection by showing a transient increase in their levels during remote ischemic preconditioning (RIPC) phase. The transient increase in reactive oxygen species levels during remote preconditioning phase may take place either through activation of K channels or through increased nitric oxide (NO) production.

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Besides functioning as thermosensors, transient receptor potential vanilloid 1 (TRPV) channels play a pivotal role in ischemia-reperfusion injury. Transient receptor potential vanilloid 1 channel activation attenuates ischemia-reperfusion-induced injury in various organs including the heart, lungs, kidneys, and the brain. Transient receptor potential vanilloid 1 channels are expressed on the sensory neurons innervating the myocardium, ventricles of the heart, epicardial surface of the heart, endothelial cells, and the vascular smooth muscle cells.

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Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection.

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The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released.

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Apart from modulating nociception, there is vital role of TRPV channels in modulating atherosclerosis, congestive heart failure, systemic hypertension, pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV channel activation has shielding effect against the development of atherosclerosis and systemic hypertension. TRPV channel activation alleviates the formation of atherosclerotic lesions via increasing the expression of cholesterol efflux regulatory protein, UCP 2 and enhancing autophagy.

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Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection.

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Remote ischemic preconditioning (RIPC) is an intriguing process whereby transient regional ischemia and reperfusion episodes to remote tissues including skeletal, renal, mesenteric provide protection to the heart against sustained ischemia-reperfusion-induced injury. Clinically, this technique has been used in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, and heart valve surgery. The endogenous opioid system is extensively expressed in the brain to modulate pain sensation.

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Remote ischemic preconditioning (RIPC) induced by alternate cycles of preconditioning ischemia and reperfusion protects the heart against sustained ischemia-reperfusion-induced injury. This technique has been translated to clinical levels in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention and heart valve surgery. Adenosine is a master regulator of energy metabolism and reduces myocardial ischemia-reperfusion-induced injury.

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Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat.

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The cardioprotective effects of remote hind limb preconditioning (RIPC) are well established, but its mechanisms still remain to be explored. Therefore, the present study was aimed to explore the possible involvement of 5-lipoxygenase-derived leukotrienes in RIPC. The hind limb was tied by a pressure cuff and was subjected to four episodes of inflation and deflation (5min each) to induce remote hind-limb preconditioning.

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There is growing preclinical as well as clinical evidence supporting remote ischemic preconditioning (RIPC), in which short cycles of non-fatal ischemia followed by reperfusion to an organ or tissue distant from the heart elicits cardioprotection. It is the most practical, non-invasive, cost-free, and clinically compatible, secure procedure for reducing ischemia-reperfusion induced injury. The use of a conventional blood pressure cuff on the upper or lower limb in eliciting cardioprotection has expedited its clinical applicability.

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Remote hind limb preconditioning (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb preconditioning was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff.

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Ischemic conditioning is an intrinsic protective mechanism in which repeated short episodes of reversible ischemia protects the tissue and increases its tolerance against a subsequent longer period of ischemia (index ischemia). Bradykinin is a physiologically and pharmacologically active peptide of the kallikrein-kinin system. Besides the involvement of bradykinin in a variety of physiological and pathological responses such as pain, inflammation and in cardiovascular system as a potent vasodilator, it also acts as an endogenous cytoprotective mediator in the ischemic tissue.

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TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis.

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In silico techniques in drug discovery may rationalise and speed up the identification of lead molecules from nature. Drug discovery from medicinal plants has mostly been confined to indications in accordance with their ethnical use only. However, the availability of multiple phytoconstituents in medicinal plants suggests that these may be much more useful beyond their traditional uses and in the management of chronic diseases, along with their comorbidities.

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