Elucidation of the influence of the CaV2.2 calcium channel on ALS disease progression in the SOD1*G93A mouse model.

Xiaozheng Anshen Formula alleviates podocyte injury in diabetic kidney disease by restoring autophagy flux via inhibiting TRPC6-mediated calcium signaling.

Infection-related glomerulonephritis (IRGN) is the leading cause of acute glomerulonephritis (GN) in children worldwide, particularly in low- and middle-income countries. To provide evidence-based care, the Glomerular Disease Workgroup of the Asian Pediatric Nephrology Association (AsPNA) convened a panel of experts to develop recommendations on diagnosis, evaluation and management of pediatric IRGN. Following a comprehensive literature search, available evidence was graded using the AAP-GRADE approach, and recommendations finalized through Delphi consensus. The panel recommends diagnosing acute GN in children presenting with hematuria and proteinuria, if accompanied with edema, oliguria, or hypertension. Postinfectious GN is suspected in patients with acute GN with recent streptococcal or staphylococcal infection and transient hypocomplementemia. The evaluation includes urinalysis, kidney function tests, serum albumin, complement C3, blood counts and kidney ultrasonography. Kidney biopsy is required for patients with atypical features, nephrotic syndrome, persistently low C3 beyond 12weeks, and/or rapidly progressive GN. Therapy is chiefly supportive, including fluid and salt restriction in patients with edema or hypertension, diuretics for volume overload, and calcium channel blockers for stage 2 hypertension. Patients with significant edema, severe hypertension, or acute kidney injury require inpatient monitoring. Patients with staphylococcus-associated GN infective endocarditis associated GN and shunt nephritis require therapy with antibiotics. Immunosuppressive therapy is suggested in patients with crescentic IRGN or rapidly progressive course. All patients with IRGN, particularly those with crescentic GN or rapidly progressive GN, require long-term monitoring of serum creatinine, urinalysis and blood pressure. These guidelines intend to provide a structured, evidence-informed approach for the management of patients with IRGN.

This review addresses an increasingly recognized but still underdiagnosed group of patients presenting for noncardiac surgery with angina with nonobstructive coronary arteries (ANOCA) driven by coronary vasomotor dysfunction (CVDys). It synthesizes current knowledge on the pathophysiology, clinical presentation, diagnosis, and treatment of CVDys - encompassing endothelial dysfunction, epicardial and microvascular spasm, and structural and functional coronary microvascular dysfunction - and provides anesthesiologists with phenotype‑guided recommendations for preoperative assessment, intraoperative management, and postoperative care. Large angiographic cohorts indicate that up to 40% of patients with angina have ANOCA, with CVDys identifiable in most patients and associated with increased mortality and major adverse cardiovascular events. Contemporary guidelines acknowledge ANOCA, advocate noninvasive perfusion imaging and invasive coronary function testing for endotype definition, and recommend endotype‑tailored therapies such as statins, angiotensin-converting enzyme inhibitors, beta‑blockers, and calcium channel blockers, alongside with perioperative strategies emphasizing symptom stability, functional capacity, meticulous hemodynamic control, stress reduction, and continuation of disease‑modifying and antianginal therapy. CVDys is particularly prevalent in females and often associated with atypical symptoms, diagnostic delay, psychological burden, and impaired quality of life. A structured, phenotype‑driven anesthetic approach - prioritizing stable hemodynamics, avoidance of vascular spasm triggers, preservation of euvolemia and oxygen delivery, multimodal analgesia, perioperative stress reduction, early recognition of ischemic symptoms, and close collaboration with cardiology - may reduce ischemic events and improve outcomes in this high risk but frequently overlooked population.

False-positive iFOBT in colorectal cancer screening: Association with prescription drug use in The Malaysian Cohort.

Voltage-gated sodium channels are essential ionic-conductance pathways in the nervous system, which play an irreplaceable role in modulating neuronal excitability and signal transduction. This review comprehensively analyzes the molecular mechanisms and pathophysiological significance of voltage-gated sodium channels, with particular emphasis on elucidating the molecular-action mechanisms of the distinct subtypes of these channels, including Nav1.1, Nav1.2, and Nav1.6, across various neurological disorders such as familial hemiplegic migraine, epilepsy, autism spectrum disorder, and retinal dysfunction. This review also provides a comprehensive overview of the pathogenic mechanisms associated with voltage-gated sodium channels, and systematically clarifies the evolutionary pathway of treatment strategies from conventional to innovative approaches. It analyzes two major categories of conventional sodium channel blockers and their applications: antiepileptic drugs (such as carbamazepine, lamotrigine, and phenytoin) and antiarrhythmic drugs (such as lidocaine, flecainide, and quinidine). However, these conventional blockers show limitations because of the lack of selectivity, driving research toward more precise therapeutic directions. Additionally, this review evaluates gabapentin, cannabidiol, and calcium channel blockers with different mechanisms of action. These drugs modulate neuronal excitability from multiple perspectives, providing diverse options for symptom relief. This review also highlights advances in gene therapy for specific diseases, such as STK-001, which promotes effective splicing of the sodium channel voltage-gated type 1 alpha subunit ( SCN1A ) gene, and ETX101, which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors. These two agents provide targeted therapeutic solutions for Dravet syndrome. Furthermore, this review summarizes some innovative therapeutic agents in clinical trials, including PRAX-222 (for SCN2A gain-of-function mutation-related epilepsy), which has received Food and Drug Administration orphan drug designation, and the selective Nav1.6 inhibitor NBI-921352 (for SCN8A -related epilepsy). Collectively, this review comprehensively compares the advantages and disadvantages of conventional drugs and gene therapy and envisions future treatment strategies that integrate the strengths of both approaches, facilitating personalized precision medicine to provide more accurate and effective treatment options for patients with ion channel diseases.

Integrative network toxicology and multi-omics analysis reveals potential mechanisms of imidacloprid-induced neurotoxicity in SH-SY5Y cells and Caenorhabditis elegans.

Pathophysiology and pharmacotherapy of cardiovascular complications in metabolic syndrome.

Exploring the knowledge and practice of calcium channel blocker overdose management among South African Emergency Medicine doctors.

Impact of Different Antihypertensive Drug Classes on Incident Dementia in Older Adults: A Systematic Review and Meta-Analysis.

Impaired autophagy from TRPV4 activation drives α-synuclein pathology in a Parkinson's disease model: A toxicological insight.

Exploring NPM1P51 as a key biomarker for glaucoma by integrating differential gene expression analysis and artificial neural network models.

Photodynamic therapy remodels the prostate cancer microenvironment by suppressing cancer-associated fibroblast-mediated calcium signaling.

Drug-induced gingival overgrowth (DIGO) is a multifactorial adverse effect associated with calcium channel blockers and antiepileptic drugs, yet genetic susceptibility-particularly in Asian populations-remains poorly defined. We performed whole-genome sequencing in 74 Thai individuals, including 36 DIGO cases and 38 drug-exposed nonresponder controls. A genome-wide association study was conducted with adjustment for amlodipine exposure, which showed a significant association with DIGO. Complementary analyses included gene-based testing using Multi-marker Analysis of GenoMic Annotation, fine-mapping with Sum of Single Effects, haplotype analysis, and receiver operating characteristic-based risk modeling. Although no single nucleotide polymorphisms (SNPs) reached genome-wide significance, we identified 350 lead SNPs across 34 genes showing strong associations with DIGO (p < 0.001). After multiple-testing correction, six genes/SNPs remained statistically significant (p < 0.05), representing the most robust findings. Haplotype analysis implicated TTC7B, RWDD1, TOM1L1, C1QL2, and BBS1 as DIGO risk genes. These genes, not previously linked to DIGO, are involved in cellular trafficking, phosphoinositide signaling, ciliary function, and protein regulation. Our findings indicate that DIGO susceptibility is driven by genetically determined cellular response pathways in the presence of amlodipine rather than by pharmacokinetic mechanisms. The absence of associations with CYP2C9 and HLA variants previously reported in other populations highlights the importance of ethnically diverse pharmacogenomic studies.

p300/Ahnak1 promotes the depression of ICa,L of atrial myocytes induced by aging.

Association between antihypertensive medications and hepatocellular carcinoma risk in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis.

Low-voltage-activated (LVA, T-type, or CaV3), calcium-selective channels open in response to modest depolarizations, just above the resting membrane potential, supporting neuronal burst-firing patterns and spontaneous firing in cardiac pacemaker cells. How LVA-channels open at low voltages is unclear: traditional gating-current experiments suggest that LVA-channel voltage-sensing domains (VSDs) paradoxically require stronger depolarization to activate than pore opening. Using voltage-clamp fluorometry, we find that the activation of all four VSDs in human CaV3.1-channels precedes opening in voltage, solving the longstanding conundrum. We also uncover confounding effects of La3+ (used for gating-current measurements) on VSD function and clarify the role of distinct LVA-channel structure S6Cyto. CaV3.1-VSDs operate within a narrow voltage-range, resembling the VSDs of related NaV-channels more than those of other CaV-channels. Likely, NaV-like VSDs emerge before sodium selectivity.

Overexpression of GJB1-13k induces mitochondrial calcium overload and triggers apoptosis and GSDME-mediated pyroptosis in cervical cancer.

Hypertension is present in 90% of individuals with heart failure with preserved ejection fraction (HFpEF) and is a major modifiable risk factor for the development of HFpEF. However, randomized controlled trial evidence for hypertension management in HFpEF is limited. In a double-blind, randomized, crossover trial, we studied the effect of amlodipine 5 to 10 mg versus metoprolol succinate 100 to 200 mg (doses previously demonstrated to have comparable antihypertensive efficacy) for 4 weeks among adults with HFpEF and hypertension, without contraindications to initiating or withholding either drug. The primary outcome was the difference in mean home systolic BP during the final week of each treatment. The mean age of the 50 enrolled participants was 72±9 years, 34 (68%) were women, 33 (66%) were of Black race, mean blood pressure was 144±15/78±9 mm Hg, and 23 (46%) were receiving β-blockers before enrollment. Compared with metoprolol, systolic blood pressure was 4 (95% CI, -7 to -1; P=0.017) mm Hg lower with amlodipine. In addition, peak oxygen uptake during exercise was 1.2 (95% CI, 0.3-2.0; P=0.008) mL/min per kg higher, physical activity was 0.1 (95% CI, 0.01-0.1; P=0.019) metabolic equivalents of task/d higher, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 200 (95% CI, -291 to -109; P<0.0001) pg/mL lower with amlodipine versus metoprolol. There was no significant difference in septal E/e', myocardial strain, or systemic vasodilatory reserve. The frequency and severity of adverse events were similar across treatments. Our findings support the use of dihydropyridine calcium channel blockers as a preferred alternative to β-blockers for the management of hypertension in HFpEF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04434664.

Atomoxetine Hydrochloride impairs human sperm quality and function via disruption of calcium homeostasis and PKC signaling: A combined network pharmacology and in vitro study.