Pharmacomodulation of membrane channels is an essential topic in the study of physiological conditions and disease status. Transient receptor potential (TRP) channels are one such family of nonselective cation channels that have an important influence. In mammals, TRP channels consist of seven subfamilies with a total of twenty-eight members. Evidence shows that TRP channels mediate cation transduction in neuronal signaling, but the full implication and potential therapeutic applications of this are not entirely clear. In this review, we aim to highlight several TRP channels which have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy. Recent findings suggest that TRPM (melastatin), TRPV (vanilloid), and TRPC (canonical) are of particular relevance to these phenomena. The research reviewed in this paper validates these TRP channels as potential targets of future clinical treatment and offers patients hope for more effective care.

Acid-sensing ion channels (ASICs) have an important influence on human physiology and pathology. They are members of the degenerin/epithelial sodium channel family. Four genes encode at least six subunits, which combine to form a variety of homotrimers and heterotrimers. Of these, ASIC1a homotrimers and ASIC1a/2 heterotrimers are most widely expressed in the central nervous system (CNS). Investigations into the function of ASIC1a in the CNS have revealed a wealth of information, culminating in multiple contemporary reviews. The lesser-studied ASIC2 subunits are in need of examination. This review will focus on ASIC2 in health and disease, with discussions of its role in modulating ASIC function, synaptic targeting, cardiovascular responses, and pharmacology, while exploring evidence of its influence in pathologies such as ischemic brain injury, multiple sclerosis, epilepsy, migraines, drug addiction, etc. This information substantiates the ASIC2 protein as a potential therapeutic target for various neurological, psychological, and cerebrovascular diseases.

Alzheimer’s disease remains a prevailing neurodegenerative condition which has an array physical, emotional, and financial consequences to patients and society. In the past decade, there has been a greater degree of investigation on therapeutic small peptides. This group of biomolecules have a profile of fundamentally sound characteristics which make them an intriguing area for drug development. Among these biomolecules, there are four modulatory mechanisms of interest in this review: alpha-, beta-, gamma-secretases, and amylin. These protease-based biomolecules all have a contributory role in the amyloid cascade hypothesis. Moreover, the involvement of various biochemical pathways intertwines these peptides to have shared regulators (i.e., retinoids). Further clinical and translational investigation must occur to gain a greater understanding of its potential application in patient care. The aim of this narrative review is to evaluate the contemporary literature on these protease biomolecule modulators and determine its utility in the treatment of Alzheimer’s disease.

Hepatitis E virus (HEV) is a global cause of viral hepatitis. While genotypes 1 and 2 cause acute hepatitis in Asia and Africa, genotypes 3 and 4 lead to sporadic acute or chronic hepatitis in America and Europe. Pregnant women, immunosuppressed individuals, and those with chronic liver disease face a higher risk of severe outcomes. HEV recombinant vaccine is approved for outbreak use in China but awaits Food and Drug Administration approval in the USA. This systematic review and meta-analysis aims to assess the safety and efficacy of the HEV vaccine. We conducted a systematic search in Medline, Cochrane, Scopus, and Embase, employing specific terms for the recombinant HEV vaccine. Eligibility criteria involved all-age individuals receiving recombinant HEV vaccine in randomized controlled trials. Covidence software was used to screen studies, and data extraction encompassed study characteristics, baseline data, and efficacy outcomes by four reviewers. Bias evaluation was completed using Cochrane’s RoB 2 tool. Statistical analysis involved use of Revman v5.4 with a random effect model, considering P < 0.05 as statistically significant. Heterogeneity was assessed using the I² test. The analysis revealed a statistically significant difference in HEV vaccine efficacy compared to placebo (odds ratio [OR]: 25.16, 95% confidence interval [CI] 9.21, 68.75, P < 0.00001) with a substantial reduction in hepatitis E cases (OR: 0.04, 95% CI 0.01, 0.11, P < 0.00001). In terms of safety, the HEV vaccine exhibited a significant increase in injection pain (OR: 1.56, 95% CI 1.03, 2.36, P = 0.04) and injection bruising (OR: 3.62, 95% CI 1.76, 7.48, P = 0.0005). No statistically significant differences were observed in fever (OR: 1.03, 95% CI 0.86, 1.23, P = 0.76) or headache (OR: 1.15, 95% CI 0.72, 1.84, P = 0.56). Local events significantly increased with the vaccine (OR: 1.50, 95% CI 1.38, 1.63, P < 0.00001). There were no significant differences in systemic events (OR: 1.06, 95% CI 0.86, 1.31, P = 0.59) or serious adverse events (OR: 0.58, 95% CI 0.16, 2.07, P = 0.40). Our systematic review and meta-analysis demonstrates the significant and favorable impact of the recombinant HEV vaccine on the reduction of HEV cases. However, safety considerations are notable, as the vaccine is associated with a significant increase in injection-related pain and bruising. While localized adverse events were more frequent with the vaccine, there were no statistically significant differences in systemic events, serious adverse events, fever, or headache compared to placebo. These findings emphasize the overall effectiveness of the HEV vaccine in preventing HEV infections but highlight the need for careful monitoring and consideration of potential localized side effects.

Cyanide (CN) is a potent, fast-acting toxicant that impacts endogenous biomolecules in the nervous system, including acid-sensing ion channels (ASICs), which play a vital role in various neurological and psychological conditions. Here, we demonstrate that CN rapidly potentiates ASIC currents in cultured mouse cortical neurons in a dose-dependent manner while causing a leftward shift in the pH dose–response curve. Notably, this potentiation was unaffected by a 30-min CN treatment or the presence of ATP in the recording pipette. Further investigations into the role of zinc revealed that TPEN, a high-affinity zinc chelator, did not enhance ASIC currents following CN pretreatment, nor did CN influence the potentiation of ASIC currents induced by TPEN. Low-affinity zinc blocked the potentiation of ASIC currents by CN. CN potentiated ASIC currents in cortical neurons from ASIC2 but not from ASIC1a knockout mice. In experiments with CHO cells expressing homomeric ASIC1a and heteromeric ASIC1a/2, CN potentiated ASIC1a currents but had no effect on homomeric ASIC1b, ASIC2a, or ASIC3 channels. Mutating lysine 133 (K133) to arginine (R) in the extracellular domain of ASIC1a abolished CN’s effect, suggesting that CN potentiates ASIC1a currents primarily via high-affinity zinc binding, with K133 being critical for this modulation.