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Inhibiting thromboinflammation via interleukin-4 binding to platelet glycoprotein VI and suppression of thrombosis.

Inflammation and coagulation are intricately linked. Although some studies have documented proinflammatory drivers of coagulation, the role of anti-inflammatory cytokines and the underlying mechanisms in the modulation of coagulation, platelet function, and thrombosis remains poorly characterized. In this study, we demonstrate that interleukin-4 (IL-4), an anti-inflammatory cytokine, plays a crucial role in regulating platelet function and thrombus formation. IL-4 inhibited collagen-induced calcium mobilization, P-selectin expression, ATP release, integrin αIIbβ3 activation, platelet spreading

Minimally Invasive, Echocardiography-Guided Mouse Model of Degenerative Mitral Regurgitation Recapitulates Cardiac Remodeling and Arrhythmogenesis.

BACKGROUND: Degenerative mitral regurgitation (MR) is a progressive valvular disorder that causes atrial enlargement, cardiac remodeling, he … astolic volume and reduced compliance. RNA sequencing of left atrial tissues revealed enrichment of calcium signaling, apoptosis, and shear stress pathways. Histology confirmed increased cardiomyocyte apoptosis, accompanied by Connexin-43 downregulation and elevated ryanodine receptor 2 phosphorylation. Programmed atrial pacing induced atrial fibrillation in MR mic …

In silico and in ovo model evaluation of thymol as an anticryptosporidial agent.

Cryptosporidiosis constitutes a serious public health problem, notably in immunocompromised individuals, while effective therapeutic options remain limited. The objective of the present work was to evaluate the anticryptosporidial activity of thymol through in silico and in ovo approaches. Molecular docking assessed thymol interactions with four key Cryptosporidium targets involved in essential metabolic pathways: glycolysis [lactate dehydrogenase (LDH)], protein biosynthesis [lysyl-tRNA synthetase (LysRS)], nucleotide synthesis [inosine monophosphate dehydrogenase (IMPDH)], and calcium-depend

Витамин D и здоровье мозга.

Витамин D широко известен своим влиянием на гомеостаз кальция и фосфата в организме и его участием в поддержании мускулоскелета. В своей активной форме, 1,25-дигидрокси холекалциферол, этот витамин оказывает иммуномодулятивное воздействие как на врожденную, так и на адаптивную иммунную систему. Активная форма витамина D играет нейрозащитную роль в центральной нервной системе, подчеркивая ее важность для поддержания здоровья мозга. В исследованиях отмечается роль витамина D в формировании антиоксидантов, снижении цитокина, способствующего воспалению, снижении окислительного стресса, улучшении м

Совпадение в аннотации оригинала
Vitamin D is widely known for its influence on the homeostasis of calcium and phosphate levels in the body and its involvement in maintainin … eurotrophic factors, the regulation of cytokines, the synthesis of neurotransmitters, intracellular calcium signaling, and the expression of genes involved in neuronal differentiation. An association has been noted between vitamin D deficiency and the risk of developing several neuronal diseases, including Parkinson's disease, headaches, multiple sclerosis, and Alz …

MCUB Inhibits PRKN-Dependent Mitophagic Degradation of PD-L1 to Promote Immune Evasion in Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) poses a severe threat to patient survival due to its high invasiveness and metastatic potential. Although immunotherapy has revolutionized treatment strategies for MIBC, immune evasion remains a major obstacle limiting therapeutic efficacy. In this study, the mitochondrial calcium uniporter regulatory subunit (MCUB) is investigated for its role in immune evasion in MIBC. Bulk RNA-seq, scRNA-seq, and proteomic analyses revealed a progressive upregulation of MCUB from normal to MIBC tissues, and strong positive correlations are uncovered between MCUB express

SERPINB7 maintains skin barrier by regulating protein O-GalNAc glycosylation.

The skin barrier is crucial for protecting against environmental challenges, preventing water loss, and regulating immune responses. This st … imarily affects the glycosylation of calcium-related and cell adhesion-related proteins, disrupting calcium signaling and compromising cell adhesion, ultimately leading to skin barrier dysfunction. In summary, this study demonstrates that SERPINB7 maintains skin barrier through protein O-GalNAc glycosylation. These findings not only deepen our understanding of skin …

Synergistic effects of compound plant extracts and Lactobacillus plantarum on osteogenesis: prebiotic potential and mechanistic insights from metabolomics and molecular docking.

BACKGROUND: Osteoporosis is a major public health challenge and innovative dietary strategies are needed to support bone health. RESULTS: This study aimed to develop a functional food by promoting osteogenesis through the synergistic effects of compound plant extracts (CPE) and Lactobacillus plantarum. First, it was determined that CPE could promote the growth, metabolic activity, biofilm formation, calcium enrichment, and antioxidant properties of L. plantarum, improving the bioavailability of calcium. Cell experiments showed that the combined application of CPE and L. plantarum (CPEL) signi

Leptin regulates parathyroid hormone secretion through CaSR-ERK1/2 signaling.

Leptin and parathyroid hormone (PTH) are key regulators of metabolic and mineral homeostasis. Leptin, primarily secreted by adipose tissue, controls appetite and energy expenditure through its receptors in the central nervous system, while PTH maintains serum calcium and phosphate balance and skeletal integrity by acting on kidneys and bone. The calcium sensing receptor (CaSR) plays a central role in parathyroid function and PTH secretion. While clinical and experimental evidence suggests reciprocal interactions between leptin and PTH, where hyperleptinemia and disrupted leptin signaling in ob

Exposure to echimidine impairs the heart development and function of zebrafish larvae.

Pyrrolizidine alkaloids (PAs) are a class of phytotoxins that are widely distributed and can be consumed by humans through their daily diets … associated with cardiac development (including gata4, tbx5, nkx2.5 and myh6) and genes involved in calcium signaling pathways (such as cacna1aa, cacna1sa, ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a1, slc8a3 and slc8a4a). In summary, our findings demonstrate that echimidine may impair cardiac development and function in zebrafish larvae by disrupting calcium transport, …

Microwaves can kill malaria parasites non-thermally.

Malaria, which infected more than 240 million people and killed around six hundred thousand only in 2021, has reclaimed territory after the … which becomes destroyed; while several other experimental approaches demonstrate the involvement of calcium signaling pathways in the resulting effects of exposure to MW. Furthermore, parasites were protected from the effects of MW by calcium channel blockers calmodulin and phosphoinositol. The findings presented here offer a molecular insight into the elusive inte …

RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx.

Receptor-interacting protein 3(RIP3), a RIP family member, has been reported as a critical regulator of necroptosis and involves in the pathogenesis of various heart diseases. However, its role in the development of myocardial hypertrophy after pressure overload is unclear. We aimed to investigate the roles of RIP3 in pathological cardiac hypertrophy. A rat model of myocardial hypertrophy induced by the aortic banding method was used in this study. Neonatal rat cardiomyocytes (NRCMs) were stimulated with angiotensin II (Ang-II) or phenylephrine (PE) to induce neurohumoral stress. Our results s

The Mechanism of Ajmaline and Thus Brugada Syndrome: Not Only the Sodium Channel!

Ajmaline is an anti-arrhythmic drug that is used to unmask the type-1 Brugada syndrome (BrS) electrocardiogram pattern to diagnose the syndrome. Thus, the disease is defined at its core as a particular response to this or other drugs. Ajmaline is usually described as a sodium-channel blocker, and most research into the mechanism of BrS has centered around this idea that the sodium channel is somehow impaired in BrS, and thus the genetics research has placed much emphasis on sodium channel gene mutations, especially the gene SCN5A, to the point that it has even been suggested that only the SCN5

Extra Virgin Olive Oil Phenols Vasodilate Rat MesentericResistance Artery via Phospholipase C (PLC)-CalciumMicrodomains-Potassium Channels (BKCa) Signals.

Recent evidence suggests that the reason Extra Virgin Olive Oil (EVOO) lowers blood pressure and reduces the risk of developing hypertension is partly due to minor components of EVOO, such as phenols. However, little is still known about the mechanism(s) through which EVOO phenols mediate anti-hypertensive effects. The aim of the present study was to investigate the mechanisms of action of EVOO phenols on mesenteric resistance arteries. A pressure myograph was used to test the effect of EVOO phenols on isolated mesenteric arteries in the presence of specific inhibitors of: 1) BKca channels (Pa

Antipsychotic drugs elicit cytotoxicity in glioblastoma multiforme in a calcium-dependent, non-D2 receptor-dependent, manner.

Dopamine D2 -like receptor antagonists have been suggested as being potential anticancer therapeutics with specific utility for central nerv … MG, and A172. Together, these data suggest that the cytotoxicity of these D2 R antagonists involves calcium signaling mechanisms, not D2 R antagonism. Repurposing of existing drugs should focus on the former, not latter, mechanism.

Hydroxysafflor yellow A actives BKCa channels and inhibits L-type Ca channels to induce vascular relaxation.

Hydroxy-safflor yellow A (HSYA) can exert a variety of effects upon the vascular system. However, the underlying mechanisms are not clear. T … tivate BKCa channels and suppress Ca-L channels in a concentration dependent manner. The results of calcium signaling assays indicated that HSYA could reduce the intracellular free Ca2+ level. These findings demonstrate that HSYA could activate BKCa channels and inhibit Ca-L channels and reduce intracellular free Ca2+ level, which are probably important for its vas …

The regulatory protein 14-3-3β binds to the IQ motifs of myosin-IC independent of phosphorylation.

Myosin-IC (Myo1c) has been proposed to function in delivery of glucose transporter type 4 (GLUT4)-containing vesicles to the plasma membrane in response to insulin stimulation. Current evidence suggests that, upon insulin stimulation, Myo1c is phosphorylated at Ser701, leading to binding of the signaling protein 14-3-3β. Biochemical and functional details of the Myo1c-14-3-3β interaction have yet to be described. Using recombinantly expressed proteins and mass spectrometry-based analyses to monitor Myo1c phosphorylation, along with pulldown, fluorescence binding, and additional biochemical ass

CRELD1 gene variants and atrioventricular septal defects in Down syndrome.

Congenital heart defects (CHD) are seen in around 40% of the Down syndrome patients. Atrioventricular Septal Defect (AVSD) or endocardial cushion defect is commonest form of CHD in these children. CRELD1 gene is implicated in causation of sporadic AVSD. In the present study, we evaluated the association and significance of CRELD1 variants with AVSD in Down syndrome (DS) patients. Sequencing was done in blood samples from 3 groups: group I (DS with AVSD), group II (DS without AVSD) and group III (non-syndromic AVSD cases). Twenty two variants in CRELD1 gene were identified, comprising of sixtee

Synaptosomal Proteome of the Orbitofrontal Cortex from Schizophrenia Patients Using Quantitative Label-Free and iTRAQ-Based Shotgun Proteomics.

Schizophrenia is a chronic and incurable neuropsychiatric disorder that affects about one percent of the world population. The proteomic cha … ns by iTRAQ and label-free, respectively. Quantitative proteome analyses showed an imbalance in the calcium signaling pathway and proteins such as reticulon-1 and cytochrome c, related to endoplasmic reticulum stress and programmed cell death. Also, it was found that there is a significant increase in limbic-system-associated membrane protein and α-calcium/calmodul …

Altered gene expression in conjunctival squamous cell carcinoma.

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progre … a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial mic …

Calcium-ATPases: Gene disorders and dysregulation in cancer.

Ca(2+)-ATPases belonging to the superfamily of P-type pumps play an important role in maintaining low, nanomolar cytoplasmic Ca(2+) levels at rest and priming organellar stores, including the endoplasmic reticulum, Golgi, and secretory vesicles with high levels of Ca(2+) for a wide range of signaling functions. In this review, we introduce the distinct subtypes of Ca(2+)-ATPases and their isoforms and splice variants and provide an overview of their specific cellular roles as they relate to genetic disorders and cancer, with a particular emphasis on recent findings on the secretory pathway Ca(