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.

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.

Deciphering the Role of ß-Lactamase Inhibitors, Membrane Permeabilizers and Efflux Pump Inhibitors as Emerging Targets in Antibiotic Resistance.

Antimicrobial drugs have been noticed to have reduce activity effective due to upsurge witnessed in resistance of microbes. To deal with viewpoint of such a circumstance, we must seek ways to prevent it or atleast mitigate its effects in order to provide its activity against the microbes. Hence, novel antimicrobials are the one of the most promising solution for ending antimicrobial resistance. Furthermore, due to the less development of newer antimicrobials in recent years, the only way to combat microbial resistance are various synergistic approaches of exploring antimicrobial drug combinations. This combination's efficacy is due to a synergistic chemical that re-sensitizes the resistant microbial strain. It has been observed that classes of ß-lactamases inhibitors, efflux pump inhibitors and membrane permeabilizers are of particular relevance, since they can break resistance to the most commonly used antimicrobials. This review explains the readers that how these synergistic combinations can help to reduce or eliminate the microbial resistance supported with clinical evidence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01045-6.