A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.

Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.

Caspase 3/GSDME-Mediated Corneal Epithelial Pyroptosis Promotes Dry Eye Disease.

Purpose: Dry eye disease (DED) is a common ocular surface inflammatory disease with a complex pathogenesis. Herein, the role and effect of gasdermin E (GSDME) in DED pathogenesis were explored.

Methods: In vitro, flow cytometry, Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays were used to determine the effects of hyperosmotic stress on pyroptosis, apoptosis, and cell viability in human corneal epithelial cells (HCECs).

Efficacy of tranilast in preventing exacerbating cardiac function and death from heart failure in muscular dystrophy patients with advanced-stage heart failure: a single-arm, open-label, multicenter study.

Background: Transient receptor potential cation channel subfamily V member 2 (TRPV2) functions as a stretch-sensitive calcium channel, with overexpression in the sarcolemma of skeletal and cardiac myocytes leading to detrimental calcium influx and triggering muscle degeneration. In our previous pilot study, we showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide levels in two patients with muscular dystrophy and advanced heart failure. Building on this, we performed a single-arm, open-label, multicenter study herein to evaluate the safety and efficacy of tranilast in the treatment of advanced heart failure in patients with muscular dystrophy.

Suppression of epileptic seizures by transcranial activation of K-selective channelrhodopsin.

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive.

Mechanosensitive Ca channel TRPV1 activated by low-intensity pulsed ultrasound ameliorates acute kidney injury through Notch1-Akt-eNOS signaling.

Acute Kidney Injury (AKI) is a significant medical condition characterized by the abrupt decline in kidney function.Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic technique employing low-intensity acoustic wave pulses, has shown promise in promoting tissue repair and regeneration. A novel LIPUS system was developed and evaluated in rat AKI models, focusing on its effects on glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), and the Notch1-Akt-eNOS signaling pathway.

The CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.

The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.

SLC10A7 regulates O-GalNAc glycosylation and Ca homeostasis in the secretory pathway: insights into SLC10A7-CDG.

Glycans are known to be fundamental for many cellular and physiological functions. Congenital disorders of glycosylation (CDG) currently encompassing over 160 subtypes, are characterized by glycan synthesis and/or processing defects. Despite the increasing number of CDG patients, therapeutic options remain very limited as our knowledge on glycan synthesis is fragmented.

The Improvement in Sleep Quality by Zizyphi Semen in Rodent Models Through GABAergic Transmission Regulation.

: Sleep, a process physiologically vital for mental health, faces disruptions in various sleep disorders linked to metabolic and neurodegenerative risks. seed (Zizy) has long been recognized for its diverse pharmacological attributes, including analgesic, sedative, insomnia, and anxiety alleviation. : In this study, the sleep-prolonging effects of Zizy extract (100, 200 mg/kg), along with their characterizing compounds jujuboside A (JuA) (5, 10 mg/kg), were evaluated in a mouse model under a pentobarbital-induced sleep.

The Significant Therapeutic Effects of Chinese Scorpion: Modern Scientific Exploration of Ion Channels.

Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935-960. It is derived from the scorpion Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research has identified the pharmacological mechanisms behind its traditional uses, with active components like venom and proteins showing analgesic, antitumor, antiepileptic, and antithrombotic effects.

Modeling Fibroblast-Cardiomyocyte Interactions: Unveiling the Role of Ion Currents in Action Potential Modulation.

Fibrotic cardiomyopathy represents a significant pathological condition characterized by the interaction between cardiomyocytes and fibroblasts in the heart, and it currently lacks an effective cure. In vitro platforms, such as engineered heart tissue (EHT) developed through the co-culturing of cardiomyocytes and fibroblasts, are under investigation to elucidate and manipulate these cellular interactions. We present the first integration of mathematical electrophysiological models that encapsulate fibroblast-cardiomyocyte interactions with experimental EHT studies to identify and modulate the ion channels governing these dynamics.

Efficacy of Cystic Fibrosis Transmembrane Regulator Corrector C17 in Beta-Sarcoglycanopathy-Assessment of Patient's Primary Myotubes.

Limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4) is a rare disease that currently has no cure. It is caused by defects in the gene, mainly missense mutations, which cause the impairment of the sarcoglycan complex, membrane fragility, and progressive muscle degeneration. Here, we studied the fate of some β-sarcoglycan (β-SG) missense mutants, confirming that, like α-SG missense mutants, they are targeted for degradation through the ubiquitin-proteasome system.

Peptide Lv and Angiogenesis: A Newly Discovered Angiogenic Peptide.

Peptide Lv is a small endogenous secretory peptide with ~40 amino acids and is highly conserved among certain several species. While it was first discovered that it augments L-type voltage-gated calcium channels (LTCCs) in neurons, thus it was named peptide "Lv", it can bind to vascular endothelial growth factor receptor 2 (VEGFR2) and has VEGF-like activities, including eliciting vasodilation and promoting angiogenesis. Not only does peptide Lv augment LTCCs in neurons and cardiomyocytes, but it also promotes the expression of intermediate-conductance K channels (K3.

The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.

Heme, a complex iron-containing molecule, is traditionally recognized for its pivotal role in oxygen transport and cellular respiration. However, emerging research has illuminated its multifaceted functions in the nervous system, extending beyond its canonical roles. This review delves into the diverse roles of heme in the nervous system, highlighting its involvement in neural development, neurotransmission, and neuroprotection.

An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying K Channel 4 Variant to Identify Small Molecule Modulators.

Primary aldosteronism is characterised by the excessive production of aldosterone, which is a key regulator of salt metabolism, and is the most common cause of secondary hypertension. Studies have investigated the association between primary aldosteronism and genetic alterations, with pathogenic mutations being identified. This includes a glycine-to-arginine substitution at position 151 (G151R) of the G protein-activated inward rectifier potassium (K) channel 4 (GIRK4), which is encoded by the gene.

Uncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing.

Background: Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients.

Alantolactone mitigates the elevation of blood pressure in mice induced by angiotensin II by inhibiting calcium channel activation.

Background: The dried root of Inula helenium L., known as Inulae Radix in Mongolian medicine, is a widely used heat-clearing plant drug within the Asteraceae family. Alantolactone (ATL), a compound derived from Inulae Radix, is a sesquiterpene lactone with a range of biological activities.

Computational modeling design of novel NMDAR agonist for the treatment of Schizophrenia.

Schizophrenia (SZ) is a complex, chronic mental disorder characterized by positive symptoms (such as delusions and hallucinations), negative symptoms (including anhedonia, alogia, avolition, and social withdrawal), and cognitive deficits (affecting attention, processing speed, verbal and visuospatial learning, problem-solving, working memory, and mental flexibility). Extensive animal and clinical studies have emphasized the NMDAR hypofunction hypothesis of SZ. Glycine plays a crucial role as an agonist of NMDAR, enhancing the receptor's affinity for glutamate and supporting normal synaptic function and plasticity, that is, signal transmission between neurons.

Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis.

Immune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury.

Targeting ion homeostasis in metabolic diseases: molecular mechanisms and targeted therapies.

The incidence of metabolic diseases-hypertension, diabetes, obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and atherosclerosis-is increasing annually, imposing a significant burden on both human health and the social economy. The occurrence and development of these diseases are closely related to the disruption of ion homeostasis, which is crucial for maintaining cellular functions and metabolic equilibrium. However, the specific mechanism of ion homeostasis in metabolic diseases is still unclear.

Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.

N-Demethylsinomenine Relieves Neuropathic Pain in Male Mice Mainly via Regulating α2-Subtype GABA Receptors.

Aims: N-Demethylsinomenine (NDSM) demonstrates good analgesic efficacy in preclinical pain models. However, how NDSM exerts analgesic actions remains unknown.

Methods: We examined the analgesic effects of NDSM using both pain-evoked and pain-suppressed behavioral assays in two persistent pain models.

Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer's disease.

Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer's disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation.

Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction.

Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients' quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we present a spatially confined conduit strategy, designed to enhance the self-organization of regenerating nerves after truncation.

Research progress on pathogenesis and treatment of febrile seizures.

Febrile seizures (FSs) are the most common pediatric neurological disorder, affecting approximately 5 % of children aged 6 months to 5 years. While most FSs are self-limiting and benign, about 20-30 % present as complex FSs (CFSs), which pose a risk of acute brain injury and the development of temporal lobe epilepsy. Various factors, including age, geographical distribution, and type of infection influence the occurrence of FS.