siRNA as potential therapeutic strategy for hypertension.

Hypertension, a well-known cardiovascular disorder noticed by rise in blood pressure, poses a significant global health challenge. The development RNA interfering (RNAi)-based therapies offers a ground-breaking molecular tool, holds promise for addressing hypertension's intricate molecular mechanisms. Harnessing the power of small interfering RNA (siRNA), researchers aim to selectively target and modulate genes associated with hypertension. Furthermore, they aim to downregulate the levels of mRNA by activating cellular nucleases in response to sequence homology between the siRNA and the corresponding mRNA molecule. As a result, genes involved in the cause of disorders linked to a known genetic background can be silenced using siRNA strategy. In the realm of hypertension, siRNA therapy emerges as a potential therapy for prognostics, diagnostics and treatments. It plays an important role in execution of targeting suppression of genes involved in vascular tone regulation, sodium handling, and pathways contributing to high blood pressure. A clinical trial involving intervention like angiotensinogen siRNA (AGT siRNA) is currently being carried out to treat hypertension. Genetic correlations between uromodulin (UMOD) and hypertension are investigated as emerging Non AGT siRNA target. Furthermore, expression of UMOD is responsible for regulation of sodium by modulating the tumor necrosis factor-α and regulating the Na + -K + -2Cl-cotransporter (NKCC2) in the thick ascending limb, which makes it an important target for blood pressure regulation.

Zebrafish Experimental Animal Models for AD: A Comprehensive Review.

AD disease (AD) is a multifaceted and intricate neurodegenerative disorder characterized by intracellular neurofibrillary tangle (NFT) formation and the excessive production and deposition of Aß senile plaques. While transgenic AD models have been found instrumental in unravelling AD pathogenesis, they involve cost and time constraints during the preclinical phase. Zebrafish, owing to their simplicity, well-defined behavioural patterns, and relevance to neurodegenerative research, have emerged as a promising complementary model. Zebrafish possess glutaminergic and cholinergic pathways implicated in learning and memory, actively contributing to our understanding of neural transmission processes. This review sheds light on the molecular mechanisms by which various neurotoxic agents, including okadaic acid (OKA), cigarette smoke extract, metals, and transgenic zebrafish models with genetic similarities to AD patients, induce cognitive impairments and neuronal degeneration in mammalian systems. These insights may facilitate the identification of effective neurotoxic agents for replicating AD pathogenesis in the zebrafish brain. In this comprehensive review, the pivotal role of zebrafish models in advancing our comprehension of AD is emphasized. These models hold immense potential for shaping future research directions and clinical interventions, ultimately contributing to the development of novel AD therapies.

An Overview of Recent Findings that Shed Light on the Connection between Fat and Cancer.

Obesity and cancer have been found to have a direct link in epidemiological studies. Obesity raises the risk of cancer and associated chronic disorders. Furthermore, an imbalance of adipokines, like leptins, plays a crucial role in neoplasm pathogenesis, cell migration, and thereby, cancer metastasis. Also, leptin increases human epidermal growth factor receptor 2 (HER2) protein levels through the STAT3-mediated (signal transducer and activator of transcription) upregulation of heat shock protein (Hsp90) in breast cancer cells. It has been noticed that insulin and insulin-like growth factors (IGFs) act as mitosis activators in the host and cancerous breast epithelial cells. The condition of hyperinsulinemia explains the positive association between colorectal cancer and obesity. Furthermore, in prostate cancer, an alteration in sex hormone levels, testosterone and dihydrotestosterone, has been reported to occur, along with increased oxidative stress, which is the actual cause of the tumors. Whereas, there have been two interconnected factors that play a crucial role in the psychological cycle concerned with lung cancer. The review article focuses on all the prospects of etiological mechanisms that have found linkage with obesity and breast, colon, lung, and prostate cancers. Furthermore, the article has also highlighted how these new insights into the processes occur and, due to which reasons, obesity contributes to tumorigenesis. This review provides a detailed discussion on the progression, which can assist in the development of new and innovative techniques to interfere in this process, and it has been supported with insights based on evidence literature on approved clinical treatments for obesity and cancer.

Exploring Cytokines as Potential Target in Peptic Ulcer Disease: A Systematic Update.

Peptic ulcer disease (PUD) is a widespread condition that affects millions of people each year, with an incidence rate of 0.1%-1.5%, and has a significant impact on human health. A range of stimuli, such as Helicobacter pylori, non-steroidal anti-inflammatory drugs, hyperacidity, stress, alcohol, smoking, and idiopathic disease states, can produce a sore in the gastrointestinal mucosal layer. For individuals infected with H. pylori, 2%-3% remain asymptomatic throughout their life. Although PUD treatments are available, genetic variations occurring in individuals because of geographical dissimilarity and antibiotic resistance pose limitations. Specifically, inflammatory cytokine gene polymorphisms have received immense attention in recent years because they appear to affect the severity and duration of stomach inflammation, which is induced by H. pylori infection, contributing to the initiation of PUD. In such a context, in-depth knowledge of interleukins may aid in the discovery of new targets and provide precautionary approaches for the treatment of PUD. This review aims to give insights into the importance of several interleukins that cognate with PUD and contribute to ulcer progression or healing by activating or dampening the host immunity. Furthermore, the available targets with clinical evidence have been explored in this review.

An Update On Proficiency of Voltage-gated Ion Channel Blockers in the Treatment of Inflammation-associated Diseases.

Inflammation is the body's mechanism to trigger the immune system, thereby preventing bacteria and viruses from manifesting their toxic effect. Inflammation plays a vital role in regulating inflammatory mediator levels to initiate the wound healing process depending on the nature of the stimuli. This process occurs due to chemical release from white blood cells by elevating blood flow to the site of action, leading to redness and increased body temperature. Currently, there are numerous Non-steroidal anti-inflammatory drugs (NSAIDs) available, but these drugs are reported with adverse effects such as gastric bleeding, progressive kidney damage, and increased risk of heart attacks when prolonged use. For such instances, alternative options need to be adopted. The introduction of voltage-gated ion channel blockers can be a substantial alternative to mask the side effects of these currently available drugs. Chronic inflammatory disorders such as rheumatoid and osteoarthritis, cancer and migraine, etc., can cause dreadful pain, which is often debilitating for the patient. The underlying mechanism for both acute and chronic inflammation involves various complex receptors, different types of cells, receptors, and proteins. The working of voltage-gated sodium and calcium channels is closely linked to both inflammatory and neuropathic pain. Certain drugs such as carbamazepine and gabapentin, which are ion channel blockers, have greater pharmacotherapeutic activity for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. This review intends to provide brief information on the mechanism of action, latest clinical trials, and applications of these blockers in treating inflammatory conditions.