Postconditioning of AM-1241 mitigates myocardial ischemia-reperfusion injury via modulation of inflammatory, fibrosis, apoptotic and autophagy pathway in rats.

Background: Pharmacological postconditioning (PostC) is an emerging and safer cardioprotective strategy against myocardial ischemia-reperfusion injury (MIRI), involving the administration of therapeutic agents at the onset of reperfusion. Activation of the cannabinoid B receptor plays a crucial role in cardioprotection across various cardiovascular pathologies. AM-1241, a selective cannabinoid B receptor agonist, exhibits multiple pharmacological properties, including anti-oxidant, anti-inflammatory, anti-apoptotic, and cardioprotective effects.

Balancing act: Drp1 inhibition and mitochondrial homeostasis in cardiovascular diseases.

The heart is an organ that depends significantly on mitochondria to operate, since it requires a lot of energy, which mitochondria create, making them essential for the efficient functioning of the heart. The term "mitochondrial dynamics" refers to extremely dynamic organelles known as mitochondria that undergo cycles of fusion and fission to modify their appearance, distribution, and function. Drp1 or Dynamin-related protein 1, a primary fission protein, strictly regulates the elimination of damaged mitochondria by mitophagy.

Metformin ameliorates blunted cardioprotective response of ischemic postconditioning in rats subjected to high fat diet.

Background: Cardioprotective response of ischaemic postconditioning (iPoCo) is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolaemia, diabetes, hypertension, etc.

Objective: The current study investigates the effect of metformin on the blunted cardioprotective response of iPoCo in rats subjected to high fat diet (HFD).

Methodology: Wistar rats were subjected to HFD for 56 days.

Beyond conventional therapy: NOX4 as a promising target in cardiomyopathy.

Cardiomyopathy refers to disorders marked by structural and functional irregularities in the heart muscle, occurring independently of other conditions that might explain these abnormalities. The most common types are dilated and hypertrophic cardiomyopathies, while Takotsubo, restrictive, left ventricular non-compaction, and arrhythmogenic right ventricular cardiomyopathies are rarer. These conditions cause ventricular hypertrophy, fibrosis, myocardial dysfunction, and chamber dilation due to responses to stressors such as pressure overload, myocardial infarction, inflammation, diabetes, and cardiotoxic drugs.

Allele-specific expression in non-small cell lung cancer: A genome-wide investigation.

Several studies have suggested that allele-specific expression (ASE)plays a critical role in cancer initiation and progression. However, little is known about genome-wide ASE and monoallelic expression of genes in non-small cell lung cancer (NSCLC). We analysed 11,422 genes that had either at least two Single Nucleotide Variations (SNVs) or a high-confidence single SNV (depth ≥10) in metastatic NSCLC samples, and found that approximately 43 % (4935 genes) exhibited monoallelic expression in at least one sample.

Cardiac Fibroblast Receptors: A Preclinical Dive Into Their Regulatory Influence on Cardiovascular Diseases.

Cardiac fibroblasts contribute to the heart's structural, electrical, and chemical integrity. Research has shown that cardiac fibroblasts have a variety of receptors that play an essential role in heart healing and function by maintaining control of autophagy, cell growth, breakdown and renewal of extracellular matrix, as well as signalling molecule production such as growth factors, cytokines, and chemokines. Receptors like endothelin, angiotensin, and DDR2 contribute to the development of cardiac fibrosis.

Unraveling the role of brain renin angiotensin system in vascular dementia: mechanisms and therapeutic perspectives.

Dementia is a heterogeneous syndrome characterized by the progressive deterioration of various brain functions, severely impacting cognitive, emotional, and social abilities. According to a World Health Organization (WHO) report, dementia represents a pressing global health concern, with the number of affected individuals projected to triple by 2050. Among its various subtypes, vascular dementia (VD) stands as the second most common form, following Alzheimer's disease (AD).

The role of endothelin and its receptors in cardiomyopathy: From molecular mechanisms to therapeutic insights.

Cardiomyopathy is an anatomical and pathologic condition that is related to the cardiac muscle or left ventricular failure. A diverse range of illnesses known as cardiomyopathies often result in progressive heart failure with high morbidity and death rates. Primary cardiomyopathies are hereditary, mixed, or adopted.

A compendium of methods: Searching allele specific expression via RNA sequencing.

Diploid mammalian genome has paired alleles for each gene; typically allowing for equal expression of the two alleles within the cell/tissue. However, genetic regulatory elements and epigenetic modifications can disrupt this equality, leading to preferential expression of one allele. Examining high-confidence allele-specific expression (ASE) is vital for understanding genetic variations and their impact on major diseases like cancers and diabetes.

Delineating the NOX-Mediated Promising Therapeutic Strategies for the Management of Various Cardiovascular Disorders: A Comprehensive Review.

Cardiovascular disorders (CVDs) are reported to occur with very high rates of incidence and exhibit high morbidity and mortality rates across the globe. Therefore, research is focused on searching for novel therapeutic targets involving multiple pathophysiological mechanisms. Oxidative stress plays a critical role in the development and progression of various CVDs, such as hypertension, pulmonary hypertension, heart failure, arrhythmia, atherosclerosis, ischemia- reperfusion injury, and myocardial infarction.

The Neuro-Healing Frontier: Alpha-Mangostin's Potential in Alzheimer's and Parkinson's Treatment.

Neurodegenerative disorders represent a set of advancing, severe, and incapacitating conditions impacting millions globally, with a rising prevalence. Despite concerted efforts and an enhanced understanding of the intricate pathophysiology of neurodegeneration, the quest for effective treatments remains unfulfilled. Consequently, there exists a pressing clinical necessity for the exploration of innovative therapeutic approaches.

Amplification of Cardioprotective Response of Remote Ischemic Preconditioning in Rats by Quercetin: Potential Role of Activation of mTOR-dependent Autophagy and Nrf2.

Objectives: Noninvasive remote ischemic preconditioning (RIPC) is a practical, acceptable, and feasible conditioning technique reported to provide cardioprotection in myocardial ischemia-reperfusion injury (MIRI). It has been well-reported that quercetin possesses antioxidant and anti-inflammatory properties. This study investigates the modification of the cardioprotective response of RIPC by quercetin.

Unveiling myricetin's pharmacological potency: A comprehensive exploration of the molecular pathways with special focus on PI3K/AKT and Nrf2 signaling.

Myricetin can be found in the traditional Chinese medicinal plant, Myrica rubra. Myricetin is a flavonoid that is present in many vegetables, fruits, and plants and is considered to have strong antioxidant properties as well as a wide range of therapeutic applications. Growing interest has been piqued by its classification as a polyphenolic molecule because of its potential therapeutic benefits in both the prevention and management of numerous medical conditions.

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content.

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

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-β (TGF-β) 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.

Exendin-4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease.

Neurodegenerative disorders, which affect millions worldwide, are marked by a steady decline of neurons that are selectively susceptible. Due to the complex pathological processes underlying neurodegeneration, at present, there is no viable therapy available for neurodegenerative disorders. Consequently, the establishment of a novel therapeutic approach for such conditions is a clinical void that remains.

Quality by design engineered, enhanced anticancer activity of temozolomide and resveratrol coloaded NLC and brain targeting via lactoferrin conjugation in treatment of glioblastoma.

The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected.

Endless Journey of Adenosine Signaling in Cardioprotective Mechanism of Conditioning Techniques: Clinical Evidence.

Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to an interrupted supply of blood and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-β/ 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.

Linking co-expression modules with phenotypes.

The method for quantifying the association between co-expression module and clinical trait of interest requires application of dimensionality reduction to summaries modules as one dimensional (1D) vector. However, these methods are often linked with information loss. The amount of information lost depends upon the percentage of variance captured by the reduced 1D vector.

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.

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-β/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.