Targeting Abnormal Tau Phosphorylation for Alzheimer's Therapeutics.

Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: ß-amyloid (Aß) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aß plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aß, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aß-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3ß and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.

Modulation of Angiotensin-II and Angiotensin 1-7 Levels Influences Cardiac Function in Myocardial Ischemia-reperfusion Injury.

The angiotensin-converting enzyme-2 (ACE-2) alters the pathophysiology of various fatal cardiovascular diseases, including ischemic heart disease, whereas angiotensin 1-7 (Ang 1-7) exerts a wide range of actions. The effects of ischemia-reperfusion (IR) injury include damage to myocardial tissue that initiates protease action, causing cardiac cell death. Angiotensin- II (Ang-II) contributes through the renin-angiotensin system (RAS) to the IR injury, whereas Ang 1-7 paradoxically exerts a protective effect through the same. Thus, the myocardial ischemic reperfusion injury (MIRI) may be altered by the RAS of the heart. This review paper focuses on ACE-2, angiotensin-converting enzyme (ACE), and Ang 1-7 regulation in the RAS of the heart in the pathophysiology of MIRI. The treatment in such conditions using ACE-2 activator, ACE inhibitor, and Ang-II antagonists may promote vascular functions as well as cardio- protection.

Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of Transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-SMA). The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension in a rat model. PAH was induced by a single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index and oxidative stress parameters were performed. Additionally, histopathology of lung and right ventricular of heart tissue, immunohistochemistry, expression of α-SMA, endothelial nitric oxide synthase (eNOS), TGF-ß, and RT-PCR, and an in vitro study using human umbilical vein endothelial cells (HUVECs) was also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress, and increase in expression of α-SMA and TGF-ß receptor 1 compared with MCT control group rats. In HUVECs, the expression of α-SMA was increased, whereas that of eNOS decreased after TGF-ß exposure and was substantially reversed after pretreatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the eNOS/TGF-ß/α-SMA signaling pathway.

Diagnosis and Management of Latent Tuberculosis Infection: Updates.

India has the largest problem of tuberculosis (TB) infection globally (estimated at about 35-40 crores cases), and around 18-36 lakh develop active tuberculosis annually. Latent TB is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB. The progression of a latent infection to active tuberculosis increases several-fold in children < 5 years of age and in people with some or the other form of an immunocompromising condition. Therefore, to cater to this gigantic problem of tuberculosis, it is necessary to have awareness about latent tuberculosis infection (LTBI) amongst clinicians and to prioritise its diagnosis and treatment in high-risk groups. India plans to end TB well before the deadline set by the World Health organisation (WHO). However, this can only be achieved with effective strategies targeting LTBI. Multiple treatment regimens have been approved for LTBI treatment, and all have comparable efficacy. The selection of one regimen over the other depends on various factors, such as availability, risk of adverse events, age, and drug interactions. Recently, the WHO, as well as the Revised National TB Control Programme (RNTCP), have updated their guidelines on TB preventive treatment in 2020 and 2021, respectively. This review has been especially prepared to acknowledge the differences in approach to LTBI in developed and developing countries.

Role of vitamin D in management of diabetes and unresolved cardiovascular diseases.

BACKGROUND: Vitamin D deficiency is becoming a widely recognized global health issue. Serum values of 25(OH) vitamin D (<20 ng/ml) are used to identify vitamin D deficiency. By prompting vascular endothelial cells to activate their nuclear receptor in cardio-myocytes, Vitamin D regulates obesity, Renin-angiotensin system (RAS), energy consumption, and pancreatic cell function. Vitamin D deficiency has been associated with diabetes, asthma, hyperlipidaemia, and pulmonary hypertension in humans. METHODS: PubMed and Google Scholar databases were utilised to search the literature on vitamin D and related diseases. RESULT: It is also linked to an elevated risk of death and heart disease. On the other hand, meta-analyses of vitamin D intervention and trials have found no substantial changes in insulin sensitivity, lipid markers, or blood pressure, which result in the association between deficiency of vitamin D and cardiovascular disease. CONCLUSION: In this review, we present the most recent research on the effects of Vitamin D therapy on various cardiovascular diseases and diabetes, and explain the underlying mechanisms.

Natural Polyphenols in Cancer Management: Promising Role, Mechanisms, and Chemistry.

BACKGROUND: Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers. METHODS: Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only. RESULTS: Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anti-cancer activities have also been discussed. CONCLUSION: Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products.

Household secondary attack rate in mild COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has reached a staggering number of almost 280 million cases worldwide, with over 5.4 million deaths as of 29 December 2021. A further understanding of the factors related to the household spread of the infection might help to bring about specific protocols to curb such transmission. Objective: This study aims to find the secondary attack rate (SAR) and factors affecting SAR among the households of mild COVID-19 cases. Methods: An observational study was designed where data of patients admitted at All India Institute of Medical Sciences, New Delhi due to mild COVID-19 were collected, and outcome was noted after the discharge of the patient. Index cases who were the first in the household to have a positive infection only were included. Based on these data, the overall household SAR, factors related to the index case and contacts that affected transmissibility were noted. Results: A total of 60 index cases having contacts with 184 household members were included in the present study. The household SAR was measured to be 41.85%. At least one positive case was present in 51.67% households. Children below 18 years old had lower odds of getting a secondary infection compared to adults and elderly [odds ratio (OR) = 0.46, 95%CI = 0.22-0.94, p = 0.0383). An exposure period of more than a week was significantly associated with a higher risk of infection (p = 0.029). The rate of transmissibility drastically declined with effective quarantine measures adopted by the index case (OR = 0.13, 95%CI = 0.06-0.26, p < 0.00001). Symptomatic index cases contributed more to the SAR than asymptomatic primaries (OR = 4.74, 95%CI = 1.03-21.82, P = 0.045). Healthcare worker index cases had lower rates of spread (OR = 0.29, 95%CI = 0.15-0.58, P = 0.0003). Conclusion: The high SAR shows the household is a potential high-risk unit for transmissibility of COVID-19. Proper quarantine measures of all those exposed to the index case can mitigate such spread and lead to reduction of risk of COVID-19 within a household.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-ß/ Smad 2/3 signalling pathways.

OBJECTIVE: Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. METHODS: Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-ß (TGF-ß) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. KEY FINDING: Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-ß and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. CONCLUSIONS: Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-ß/Smad 2/3.

Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials.

Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections. To address the issue of regular injection, we have synthesized a fat fighting oral nano-formulation of liraglutide with a sustained release feature, which was evaluated against high fat diet (HFD) induced obesity in mice. Experimental obesity was induced in mice by feeding HFD for 26 weeks. Lir nanoparticles (NP) were fabricated with chitosan via ion-gelation technique and were coated with Eudragit@S100 to protect the drug in harsh gastric conditions. Physiochemical characterization of Eu-Lir-Cs-NP demonstrated a small particle size of 253.1 ± 1.21 nm with âˆ¼ 9.74 % loading and âˆ¼ 72.11 % encapsulation efficiency of the drug. In-vitro studies showed successful cellular uptake of NP in Caco-2 cells and were stable in various enteric fluid pH conditions. Eudragit@S100 coated chitosan NP were able to protect the drug from harsh gastric pH conditions with more than âˆ¼ 74% of recovery. Treatment of two weeks of liraglutide Eu-Lir-Cs-NP (0.1, 0.2 and 0.4 mg/kg, orally; twice daily) moderately reduces obesity in mice as evidenced by a reduction in the body weight, blood glucose, serum total cholesterol, serum triglyceride, serum resistin and serum insulin level of mice. In addition, significant reduction of liver weight, abdominal white adipose tissue, and hepatic oxidative stress were noted. Our results suggest that chitosan-based NP of liraglutide can be an effective and convenient formulation for the management of obesity.

Differential effect of basal vitamin D status in monocrotaline induced pulmonary arterial hypertension in normal and vitamin D deficient rats: Possible involvement of eNOS/TGF-ß/α-SMA signaling pathways.

Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-ß (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- ß significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.

Pain Allaying Epalrestat-Loaded Lipid Nanoformulation for the Diabetic Neuropathic Pain Interventions: Design, Development, and Animal Study.

BACKGROUND: Diabetic peripheral neuropathy is the most common complication of diabetes mellitus. Epalrestat, an aldose reductase inhibitor, has been approved for clinical therapy for diabetic peripheral neuropathic pain. In the present study, solid lipid-based nanoparticles are used for oral administration of epalrestat (E-SLN) and evaluated against diabetic neuropathic pain in a rat model. METHODS: Experimental diabetes in rats was induced by a single dose of streptozotocin (STZ) administration. The therapeutic efficiency of Epalrestat nanoparticles (0.25, 0.50, 1, and 5 mg/kg) in diabetic rats was studied. STZinduced diabetic rats were treated with different doses of E-SLN for 8 weeks. The nanoparticles were orally administered at a single dose in rats, and the various parameters related to peripheral neuropathy were evaluated and compared with the bare drug. The blood glucose level was estimated by standard glucometer, HbA1c, triglycerides, total cholesterol, and liver function test (ALT and AST) were analyzed by blood samples collected from retro-orbital plexus. Oxidative stress markers and Na+K+ATPase, TNF-α, and IL-1ß levels were measured in the homogenate of sciatic nerves. Behavioral tests were also performed by the hot plate method and tail-flick method. RESULTS: E-SLN synthesized by the micro-emulsification method was 281 ± 60 nm in size, and encapsulation efficacy was found to be 88 ± 2%. Optimized E-SLN were characterized and found to be optimum in size, spherical shape, decent encapsulation efficiency, stable at acidic gastric pH, and suitable for oral delivery. E-SLNs did not significantly reverse the STZ-induced elevated blood glucose level (FBS and PPBS), HbA1c, triglycerides, and total cholesterol but significantly improved TNF-α, IL-1ß, and increased Na+K+ATPase levels, oxidative stress marker and ALT, AST in the treated rat group as compared with the diabetic group. Doses of E-SLN, i.e. 0.5, 1.0, 2.5, and 5 mg/kg, significantly increased the tail-flick latency time and hot plate response time in a dose-dependent manner compared with the diabetic group. CONCLUSION: Thus, it is suggested that E-SLN were equally effective and less hepatotoxic compared with the standard treatment of epalrestat. To the best of our knowledge, we, for the first time, propose the orally deliverable E-SLN that ameliorates STZ-induced diabetes neuropathic pain effectively as compared with conventional epalrestat.

Co-Adjuvancy of Solasodine & CoQ10 Against High Fat Diet-Induced Insulin Resistance Rats Via Modulating IRS-I and PPAR-γ Proteins Expression.

Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i.e. SDQ10 (total 50 mg/kg) for the last 4 weeks orally once daily. Blood and tissue samples were collected by the end of study period for the biochemical and histological studies. As a result, HFD fed rats exhibited a significant increase in food and energy intake, body mass index, kidney and pancreas weight, fasting glucose, glycosylated haemoglobin, insulin level, liver enzyme ALT and AST and decrease antioxidant activity of superoxide dismutase and catalase. HFD received animals also produced a lower level of p-IRS1 and PPAR-y protein expression in western blot analysis. SDQ10 in combination successfully restored the above-mentioned complexity of insulin resistance caused by aHFD. Besides, increasesthe antioxidant activity of superoxide dismutase and catalase and normalized the architecture of kidney, pancreas and adipose tissue as well astreatment with SDQ10 raised the level of p-IRS1 and PPAR-y protein in liver tissue. As a result, supplementing with solasodine and coenzyme Q10 reversed the effect of the HFD on p-IRS1 and PPAR-y protein in liver tissue while also alleviating insulin resistance symptoms.

Caveolins: Expression of Regulating Systemic Physiological Functions in Various Predicaments.

Caveolins are membrane proteins which contains caveolae. They are present in the plasma membrane. Many researchers found that caveolae have been associated with expression of the caveolins in major physiological networks of mammalian cells. Subtypes of caveolin including caveolin-1 and caveolin-2 have been found in micro arteries of rat brain, while caveolin-3 has been found in astrocytes. Caveolin-1 and caveolae play important roles in Alzheimer's disease, cancer, ischemic preconditioning-mediated cardio-protection, postmenopausal alterations in women, and age-related neurodegeneration. Caveolin-1 may modify fatty acid transmembrane flux in adipocytes. The discovery of a link between ischemia preconditioning, cardio-protection, and endothelial nitric oxide synthase has supported cardiovascular research tremendously. Therefore, caveolins are effective in regulation of cellular, cardiovascular, brain, and immune processes. They ascertain new signalling pathways and link the functionalities of these pathways. This review paper focuses on contribution of caveolins in various conditions, caveolin expression at the molecular level and their physiological effects in many organ systems.

Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts

Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

Management of dengue with co-infections: an updated narrative review.

Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India.

An inquest into regulatory mechanism of caveolin by ischemic preconditioning against orchidectomy-challenged rat heart.

Lower level of testosterone in men is related to major risks of cardiovascular diseases. This risk may increase due to the opening of mitochondrial permeability transition pore (mPTP). The mPTP is also regulated by ischemic preconditioning (IPC) and a membrane protein known as caveolin. The cardioprotective effect of IPC is the most effective methodologies used in testosterone deficiency. Daidzein (DDZ) a caveolin inhibitor shows cardioprotective action. The experiment has been designed to evaluate the pretreated DDZ effect in IPC-mediated cardioprotective action in orchidectomy (OCZ)-challenged rat heart. The experiment was designed on male Wistar rats with/without OCZ. The level of testosterone is decreased by OCZ which reduces general body growth. Isolated heart from normal and OCZ rat was tied up on Langendorff's perfused apparatus and followed by ischemic reperfusion (IR) and IPC cycle. To investigate the cardioprotective effect of DDZ in heart with testosterone deficiency, a total of nine groups, each consisting of six rats (n = 6) were as follows: Sham, IR, IPC, IPC + OCZ, IPC + DDZ, IPC + OCZ + DDZ, IPC + sodium nitrite, IPC + OCZ + sodium nitrite, IPC + OCZ + DDZ + sodium nitrite. Hemodynamic parameters, cellular injury (infarct size, LDH, CKMB and cardiac troponin-T), oxidative stress, mitochondrial function, integrity and immunoblot analysis were assessed for each group. The experimental data showed that DDZ potentiated IPC-mediated increase in the heart rate, left ventricular diastolic pressure, coronary flow; + dp/dtmax, and - dp/dtmax. The pretreated DDZ decreases the action of LDH and CKMB, myocyte size, cardiac collagen content, infarct size and ventricular fibrillation and attenuation in oxidative stress and mitochondrial dysfunction in OCZ-challenged rat heart in all sets of experiments. Sodium nitrite, a producer of nitric oxide (NO), enhanced potentiating effects of DDZ on IPC-mediated cardioprotection in OCZ-challenged rats. These observations show that the downregulation of caveolin through impaired opening of mPTP during reperfusion and caveolin might be a potential adjuvant to IPC against cardiac injury in OCZ-challenged rats.

Caveolins; An Assailant or An Ally of Various Cellular Disorders.

Caveolae have impressive morphological highlights of the cytomembrane of mammalian cells which involve in wide diversity of cellular functions involving signaling pathways and cholesterol hastening. Caveolin proteins possess a 'scaffolding' domain which for caveolin-1 and caveolin-3 appear to act a dominant role in signal regulation through caveolae. Caveolin-1 is treated to be protein in the cytomembrane entrapped with caveolae in endothelial cells and vascular smooth muscle cells which diminish nitric oxide (NO) by fill up the calcium/calmodulin (Ca2+/CaM) confining point of endothelial nitric oxide synthase (eNOS), decrease NO generation produce endothelial dysfunction and atherosclerotic injury development. It is a cholesterol-binding layer protein associated with cell cholesterol transport and also shows cardioprotective action through ischemic preconditioning (IPC) in diabetic and postmenopausal rat heart. Additionally it is ensnared in the procedures of tumorigenesis, prostate disease, and inflammation. The present study in the paper is to explore the structural functionalities of caveolins and their contributory role in CVS disorders and various other diseases.

Mechanistic Pathways of ATP Sensitive Potassium Channels Referring to Cardio-Protective Effects and Cellular Functions.

A study of potassium channels correlates the fundamentals of mechanistic pathways and various physiological functions. The knowledge of these pathways provides the background, how to determine unit cell functions and to affect cardio protection. ATP sensitive potassium channels adjust excitability of membrane and functions as per metabolic status of cell. A lot of energy consumption primarily occurred in skeletal muscles which also express high number of potassium channels. The increase in calcium release and high heat production is occurred due to loss of potassium channels. Such type of mediations determines metabolic changes and energy required in the dissipation. IPC reduces infarct size in anesthetized mice. In ischemic-reperfusion, pressure in left ventricle was watched while contractile power recovery did not happen. It was seen that elements of intact potassium channel are fundamental for Ischemic preconditioning (IPC). If more prominent is enactment of potassium channels and their cardiologic effects create high heart rate. All the more as of late, it has been suggested that mitochondrial ATP sensitive potassium channels are critical as closing stage effectors which trigger IPC as opposed to sarcolemmal potassium channels. Nevertheless, the importance of the potassium channels reconsidered in cardio-protection in present findings. These discoveries recommend that potassium channels in the adjusting ischemic-reperfusion damage in mice. The heart rate of the mouse occurred during ischemia; enhance watchful extrapolation applied to larger warm blooded animals.

Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart.

Cardio-vascular diseases are the leading cause of morbidity and mortality. Ischemia is a state of oxygen deprivation in tissues, whereas reperfusion is restoration of blood flow in ischemic tissues. Myocardial damage of tissue during reperfusion after ischemic insult is known as myocardial ischemia-reperfusion (I/R) injury. It induces damage to cardiac muscle via increasing expression of oxygen, sodium and calcium ions which are responsible in the activation of proteases and cell death. Heart renin angiotensin system (RAS) plays an important role in the myocardial ischemia and reperfusion injury. Angiotensin (1-7) is responsible for vasodilation and angiotensin II for vasoconstriction. Here-in we reviewed how myocardial I/R injury sets in by up-regulation of angiotensin II that leads to increased infarct size, which can be reduced by the use of ACE inhibitors, ACE2 activators and angiotensin II antagonist.