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Calcium homeostasis imbalance in sepsis: molecular mechanisms and therapeutic perspectives.

Calcium ions (Ca2+) are pleiotropic signaling messengers that regulate diverse cellular processes, and their homeostasis is essential for normal physiology at cellular, tissue, and organismal levels. Accumulating evidence identifies Ca2+ dysregulation as a key driver of sepsis onset and progression. In this review, we systematically delineate the mechanisms governing intracellular Ca2+ homeostasis, focusing on coordinated regulation among the endoplasmic reticulum, mitochondria, and lysosomes. We also discuss the molecular basis of disordered Ca2+ signaling in sepsis-associated pathologies and…

Climbing fibres recruit disinhibition to enhance Purkinje cell calcium signals.

Climbing fibre (CF) inputs to Purkinje cells (PCs) instruct plasticity and learning in the cerebellum1-3. Paradoxically, CFs also excite molecular layer interneurons (MLIs)4,5, a cell type that inhibits PCs and can restrict plasticity and learning6,7. However, two types of MLI with opposing influences have recently been identified: MLI1s inhibit PCs, reduce dendritic calcium signals and suppress plasticity of granule cell to PC synapses2,6-9, whereas MLI2s inhibit MLI1s and disinhibit PCs8. To determine how CFs can activate MLIs without also suppressing the PC calcium signals necessary for pla…

Presynaptic CaV2.1 calcium-dependent facilitation enables reliable auditory information transfer.

Activity-dependent modulation of presynaptic voltage-gated Ca2+ channels (CaV2) regulates Ca2+ influx to control neurotransmitter release and neuronal circuit output. Although CaV2.1 can undergo robust Ca2+-dependent facilitation (CDF), its contribution to information processing in central neuronal circuits remains unclear. Accurate auditory information processing requires precise and reliable synaptic transmission at high activity rates in the auditory brainstem. To determine if CaV2.1 CDF is a key regulator of high-fidelity synaptic transmission, we expressed CaV2.1 splice variants that are

Cytosolic calcium oscillations in human adrenocortical cells causing primary aldosteronism.

BACKGROUND: Intracellular calcium [Ca2+]i is pivotal in driving aldosterone secretion. However, knowledge of the [Ca2+]i dynamics underlying aldosterone excess in primary aldosteronism (PA), the most common form of endocrine hypertension, is lacking due to the difficulty of obtaining aldosterone-producing adenoma (APA) cells ex vivo. METHODS: We used the Ca2+-sensitive Fura-2 dye and live confocal microscopy to investigate variations in [Ca2+]i under basal conditions and after angiotensin II (Ang II) stimulation in primary aldosterone-producing CD56+ cells, immunomagnetically isolated ex vivo…

SPG11 models reveal lysosomal calcium regulation of neural progenitor proliferation.

Lysosome dysfunction has been widely implicated in many models of neurodegeneration, but much less is understood of its involvement during b … early stages of cortical development. At the cellular level, SPG11 mutations cause accumulation of calcium in lysosomes, which reduces proliferation of neural progenitor cells and diminishes apical tight junctions. RNA sequencing analysis revealed that these phenotypes in SPG11 organoids are caused by hypoactivation of mammalian target of rapamycin (mTOR …

Calcium Metabolism, Immunity and Reproduction in Early Postpartum Dairy Cows.

Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D3 treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune response, had been investigated. Eight multiparous cows were treated with 10 mL vitamin D3 (1 million IU cholecalciferol/mL) intramuscularly on day 273 of pregnancy, while eight others remained untreated and served as controls. Placental tissues were collected post-calving, and gene exp…

IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity.

The mammalian endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) is essential for cellular homeostasis and plays … maturation, which is crucial for containing C. albicans hyphae. IRE1α facilitates early phagosomal calcium flux post-phagocytosis, which is required for phagolysosomal fusion. In macrophages lacking the IRE1α endoribonuclease domain, defective calcium flux correlates with fewer ER-early endosome contact sites, suggesting a homeostatic role for IRE1α-prom …

Intracellular calcium channels: Potential targets for type 2 diabetes mellitus?

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder. Despite the availability of numerous pharmacotherapies, a range of adverse reactions, including hypoglycemia, gastrointestinal discomfort, and lactic acidosis, limits their patient applicability and long-term application. Therefore, it is necessary to screen novel therapeutic drugs for T2DM treatment that have high efficacy but few adverse effects. AMP-activated protein kinase (AMPK) stands out as one of the most powerful targets for T2DM treatment. It can be activated through energy-sensing or calcium signaling. Medications th…

Pathological calcium influx through amyloid beta pores disrupts synaptic function.

Alzheimer's disease (AD) is characterized by profound disruption of synaptic function, with mounting evidence suggesting that amyloid-β (Aβ) oligomers disrupt calcium (Ca2+) homeostasis through membrane pore formation. While these pores are known to alter intracellular Ca2+ dynamics, their immediate impact on synaptic transmission and potential interaction with Familial AD (FAD)-associated endoplasmic reticulum (ER) dysfunction remains unclear. Here, we extend our previously developed model of presynaptic Ca2+ dynamics to examine how Aβ pores alter exocytosis and how such disruptions may manif…

Altered endoplasmic reticulum calcium loading in human PLN-R14del cardiomyopathy.

The phospholamban (PLN) R14del genetic variant causes dilated cardiomyopathy. Previous studies suggest involvement of the ER stress response and impairment of ER-related signaling pathways such as autophagy. In this study, human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) from an unrelated control subject, a PLN-R14del patient, and a corresponding isogenic control were transduced with adeno-associated virus serotype 6 (AAV6) encoding the endoplasmic reticulum calcium sensor CEPIAer. Indicator compounds for the modulation of ER calcium homeostasis showed similar character…

Coronary Artery Calcium Testing-Too Early, Too Late, Too Often.

IMPORTANCE: Traditional risk factors, enhancing factors, and risk scores help clinicians assess atherosclerotic cardiovascular disease (ASCVD) risk for primary prevention. The latest cholesterol guidelines suggest measuring coronary artery calcium (CAC) score by computed tomography (CT) in those at intermediate risk when there is uncertainty about statin initiation for primary prevention. CAC testing can improve both risk estimation and adherence to cardiovascular risk-reducing behaviors. OBSERVATIONS: As measuring CAC score has become more widely available, this article focuses on 3 situatio…

Gene-activation of surface-modified 3D printed calcium phosphate scaffolds.

Large volume bone defects that do not spontaneously heal despite surgical stabilization ("critical-sized" defects) remain a challenge to treat clinically. Recent research investigating bone regenerative implants made from 3D printed materials have shown promise as a potential alternative to current treatment methods, such as autografting, allografting, and multi-step surgical interventions. Recent work has shown that implanting 3D printed calcium phosphate cement (CPC) scaffolds loaded with bone morphogenetic protein-2 (BMP-2) can provide a one-step surgical intervention that has similar bone …

Monitoring denosumab therapy using the calcium isotope marker (CIM) technology.

Denosumab provides a well-established therapy for osteoporosis. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (BTMs) track changes in bone mineral density (BMD) and turnover. Calcium (Ca) Isotope Markers (CIM), which measure naturally occurring variations in stable Ca isotope ratios in serum (CIM_serum) and urine (CIM_urine), offer a potentially more sensitive and individualized approach for monitoring bone health and therapy responsiveness. In this pilot study, 13 postmenopausal women with DXA-confirmed osteoporosis were initiated on denosumab. Over 24 weeks, serial measure…

Gabapentin lactam induces neurodevelopmental deficits via calcium-mitochondria-ROS cascade.

Gabapentin lactam (GBP-L), a transformation product of the anticonvulsant gabapentin, persists in surface waters at concentrations reaching … reduction in axonal length of 7.84 %. Mechanistic investigations demonstrated that GBP-L activates calcium signaling pathways, triggering intracellular Ca²⁺ overload that leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and disrupted neurotransmitter homeostasis. Co-exposure with the calcium channel blocker verapami …

Наркомативность обмена кальциями натрия (NCX): проблемы и последние события.

Na+/Ca2+ обменные устройства (NCXs) являются мембранными переносчиками, имеющими решающее значение для гомеостазиса кальция в эксцизируемых тканях, особенно в центральной нервной системе. Растущие данные свидетельствуют о том, что дисфункция NCX приводит к перегрузке кальция и нейронным повреждениям в нескольких неврологических условиях. Таким образом, фармакологическая модуляция изоформов NCX (NCX1, NCX2 и NCX3) стала потенциальной терапевтической стратегией для таких расстройств, как инсульт, множественный склероз (MS), амиотропический боковой склероз (ALS), болезнь Альцгеймера (AD) и болезн

Совпадение в аннотации оригинала
Na+/Ca2+ exchangers (NCXs) are membrane transporters crucial for calcium homeostasis in excitable tissues, particularly in the central nervous system. Growing evidence indicates that NCX dysfunction contributes to calcium overload and neuronal damage in several neurological conditions. Thus, pharmacological modulation of NCX isoforms (NCX1, NCX2, and NCX3) h…

Calcium sensing receptor: A promising therapeutic target in pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by elevation of pulmonary arterial pressure and pulmonary vascular resistance. The increased pulmonary arterial pressure and pulmonary vascular resistance due to sustained pulmonary vasoconstriction and pulmonary vascular remodeling can lead to right heart failure and eventual death. A rise in intracellular Ca2+ concentration ([Ca2+]i) and enhanced pulmonary arterial smooth muscle cells (PASMCs) proliferation contribute to pulmonary vasoconstriction and pulmonary vascular remodeling. Recent studies demonstrated that extracellular calcium sensing rec…

Dentin remineralization induced by experimental composites containing calcium orthophosphate particles.

OBJECTIVES: This study aimed to verify if composites containing dicalcium phosphate dihydrate particles (DCPD) are able to induce dentin remineralization in vitro. Additionally, the mechanical properties of the materials were tested. METHODS: Four composites with 50 vol% inorganic content and 1 BisGMA: 1 TEGDMA (mols) were prepared, with different DCPD:glass ratios (50:0, 40:10, 30:20 and 0:50). Ca2 + release in water was monitored for 8 weeks using inductively coupled plasma optical emission spectrometry (n = 3). Composites were applied to artificial lesions (180 μm in depth) prepared in den…

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and…