Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the synovial joint, which leads to inflammation, loss of function, joint destruction, and disability. The disease biology of RA involves complex interactions between genetic and environmental factors and is strongly associated with various immune cells, and each of the cell types contributes differently to disease pathogenesis. Several immunomodulatory molecules, such as cytokines, are secreted from the immune cells and intervene in the pathogenesis of RA. In immune cells, membrane proteins such as ion channels and transporters mediate the transport of charged ions to regulate intracellular signaling pathways. Ion channels control the membrane potential and effector functions such as cytotoxic activity. Moreover, clinical studies investigating patients with mutations and alterations in ion channels and transporters revealed their importance in effective immune responses. Recent studies have shown that voltage-gated potassium channels and calcium-activated potassium channels and their subtypes are involved in the regulation of immune cells and RA. Due to the role of these channels in the pathogenesis of RA and from multiple pieces of clinical evidence, they can be considered therapeutic targets for the treatment of RA. Here, we describe the role of voltage-gated and calcium-activated potassium channels and their subtypes in RA and their pharmacological application as drug targets.

Behavioral and Neurological Effects of Edaravone and Noscapine in Albino Wistar Rats.

OBJECTIVE: The purpose of the study was to explore Edaravone and Noscapine in anAlCl3-induced Alzheimer's disease (AD) model. METHODS: Morris Water Maze (MWM), Novel Object Recognition (NOR), andY-maze tests with TNF-α, IL-1, IL-6, amyloid-ß, CAT, SOD and MDAlevels were performed, followed by brain histology. RESULTS: On the probe trial, the MWM demonstrated a decrease in escape latencyfollowed by an increase in the target quadrant. The NOR showeddiscrimination and recognition index scores and Y-maze, revealed arise in spontaneous alterations. TNF-α, IL-1, IL-6, amyloid-ß, CATand MDA levels increased, while SOD levels dropped. The results werefound to be significant for combination full and half doses (***p <0.001, **p < 0.01). The treated group's histology ofbrain revealed mild neurodegeneration with hippocampal pyknoticnuclei. CONCLUSIONS: Thus, Edaravone and Noscapine can be used for thetreatment of AD. .

Abbreviations: AlCl3: Aluminium chloride; AD: Alzheimer's disease; Aß: Amyloid plaques; APP: amyloid precursor protein; BACE 1: Serum beta-secretase 1; GSK3ß: Glycogen synthase kinase 3 ß; CDK 5: cyclin-dependent kinase-5; NFTs: neurofibrillary tangles; ROS: reactive oxygen species; JNK: c Jun N-terminal kinases; MWM: Morris Water Maze; NOR: Novel Object Recognition (NOR); TNF-α: Tumor necrosis factor -α; CAT: Catalase; SOD: Superoxide Dismutase; MDA: Malondialdehyde.

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.