Neuritin protects spiral ganglion neurons via NKA-Ca²⁺ homeostasis and CaMKII/MAPK suppression.

Low-dose telmisartan protects against myocardial ischemia/reperfusion injury via dual mechanisms: AMPK activation and AMPK-independent calcium homeostasis.

Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche.

Synaptic plasticity relies on precise spatial and temporal compartmentalization of signaling within dendritic spines, presynaptic terminals, and axonal domains. This compartmentalization is usually reinforced through activity-dependent remodeling of spine geometry, cytoskeletal scaffolds, calcium handling, and local protein synthesis, allowing plasticity signals to remain localized and terminate appropriately. Here, a unifying framework is proposed in which neurodegenerative diseases emerge when the capacity to maintain and renew these compartments declines. Ageing and glial dysregulation may act as major biological drivers of this process by altering dendritic spine structure, calcium homeostasis, metabolic support, neurotransmitter clearance, and activity-dependent synaptic remodeling. In this state, plasticity induction remains largely preserved, but signaling becomes spatially diffuse and temporally prolonged, imposing chronic structural and energetic stress on synapses and axons. Proteins such as tau and alpha synuclein, which normally support cytoskeletal organization and dynamic phase separated assemblies, may become destabilized under these conditions leading to pathological aggregation. This framework provides an explanation for early synaptic dysfunction, selective neuronal vulnerability, long presymptomatic phases, network-level disease propagation, the protective effects of education and cognitive engagement, and the limited efficacy of proteinopathy centric therapeutic strategies. Neurodegeneration may be conceptualized as a failure of synaptic compartmentalization, with protein aggregation arising downstream of this primary vulnerability.

Associations of Estrogen Receptor 1 and Vitamin D Receptor Gene Polymorphisms with Bone Resorption During Pregnancy and Early Postpartum in a Mexican Cohort.

Activation of sarco/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) reduces brain injury and improves cognitive function following ischemic stroke.

Metabolic bone disorders are common, albeit underestimated, causes of fractures and chronic bone pain in internal medicine. They can remain asymptomatic for long periods and are frequently only diagnosed when insufficiency fractures occur. The aim of this review article is to discuss common and rare metabolic bone disorders and to outline apractice-oriented diagnostic approach. Narrative review of current literature with particular emphasis on clinically relevant differential diagnoses and diagnostic algorithms. In addition to secondary osteoporosis, disorders of calcium and phosphate metabolism play acentral role. Important differential diagnoses include primary hyperparathyroidism, genetic osteopathies, hypophosphatasia, and fibroblast growth factor23 (FGF23)-mediated hypophosphataemia. Crucial for diagnosis are astructured medical history, the measurement of calcium, phosphate, magnesium, parathyroid hormone and alkaline phosphatase, as well as, where necessary, further parameters such as tubular maximum for phosphate reabsorption per glomerular filtration rate (TMP/GFR) and FGF23. Magnetic resonance imaging is essential for detecting insufficiency fractures. Asystematic approach to the diagnosis of metabolic bone diseases is crucial, as this directly determines different therapeutic implications, and specific treatment options are increasingly becoming available.

Exploring the immunological functions of calreticulin 3a from Scomber japonicus (SjCalr3a): insight into antimicrobial defense, cytoprotection, and pro-inflammatory responses.

Plant derived natural products and medicinal herbs have recently gain more attention as therapeutic agents to treat various ailments. The current study aims to explore the potential role of C. papaya's natural intervention in reducing the asbestos-induced pulmonary damage. A total of 32 male albino rats were grouped into NC, PC, STD (Montelukast Sodium 10 mg/kg), and C.P (500 mg/kg) groups, having eight animals in each group. Experimental units from the PC were exposed to asbestos fibers in a glass chamber for 2-3 h daily. Biological tissues for histopathology were preserved in formalin, lung tissue for qRT-PCR was immersed in TRIzol, broncho-alveolar lavage fluid (BALF) was collected for protein analysis, and serum was separated for oxidative biomarkers. Data was analyzed by the ANOVA and Tukey's test, and GraphPad Prism (v 8.0) was used for graphical representation. Results of the study revealed that after treatment, serum antioxidant markers were significantly enhanced in the C.P group (p ≤ 0.05), whereas oxidative markers were reduced significantly in the C.P group (p ≤ 0.05). Markers of protein analysis from BALF and wet-to-dry ratio increased in the PC group, but a significant decline was seen in the C.P group (p ≤ 0.05). Results of qRT-PCR showed upregulation of oxidative response pathway molecules and apoptotic markers in PC such as NRF1, DUOX, DUOXA1, DUOXA2, BAX, BID, CASP9, CYT-C, and NFE-2 L2. Parallel to this, an elevated response from antioxidant markers and calcium homeostasis regulators was seen in the C.P-treated group. Microscopic insights revealed normal parenchyma of the lung and trachea in the NC group, which was worsened with thickened airways, fibrotic alveolar walls, and lodged fibers of asbestos seen in the tissue samples of the PC group. Treatment with C. papaya revealed a restored histopathological profile with better alveolar architecture and mitigated effects of asbestos fibers. The results of this study suggest that C. papaya exhibits strong antioxidant potential to mitigate oxidative stress caused by inorganic source.

Owing to transformative improvements in diagnosis and treatment, survival rates for cancer patients have improved significantly across the globe. However, toxicity induced by oncotherapy remains a major concern and markedly affects disease prognosis. In recent years, research on the association between circular RNAs (circRNAs) and oncotherapy-induced toxicity has received extensive attention. CircRNAs are a class of single-stranded closed-loop molecules that play a regulatory role in the occurrence and development of tumors. An integral role of circRNAs in the development of cancer treatment-induced toxicity, as well as in pathological processes such as oxidative damage, mitochondrial damage, apoptosis, dysregulation of calcium homeostasis, and dysregulation of vascular homeostasis has been deciphered. With regards to chemotherapy, radiotherapy, and immunotherapy for cancer treatment, circRNAs play crucial functions in modulating the effects of oncotherapy-induced toxicity. The current review focuses on the mechanisms by which circRNAs function in regulating cancer treatment-induced toxicity, which leads to apoptosis, mitochondrial damage, oxidative stress, DNA damage, and fibrosis. In addition, this review summarizes the potential circRNA biomarkers, treatment strategies and future challenges, which may help translate circRNA research into clinical practice for early detection and improvement of cancer treatment-induced toxicity in the future.

Experimental and computational analysis of SERCA inhibition by naphthoquinone derivatives.

Calmodulin (CaM) is a central calcium sensor and signaling hub that critically governs stem cell fate. However, directly intracellular modulation of CaM remains challenging due to its activity is tightly coupled to finely balanced calcium homeostasis, and conventional chemicals or biomaterials have limited ability to access or target it. Here, we introduce a novel two-dimensional, porous, covalent triazine-based framework, CTF-Ca, synthesized under ambient conditions, that offers a new strategy for intracellular CaM regulation. Unlike conventional approaches, CTF-Ca bypasses membrane calcium channels, enabling direct calcium influx into mesenchymal stem cells (MSCs) and triggering robust, sustained activation of the Ca2+/CaM signaling pathway. This activation markedly enhances osteogenic differentiation in MSCs. Remarkably, CTF-Ca also compensates for suppressed CaM function, restoring osteogenic potential in MSCs even under CaM-inhibited conditions. This compensatory effect was further demonstrated in C2C12 myogenic progenitor cells, a skeletal muscle model characterized with high endogenous CaM expression, where CTF-Ca rescued myotube formation in CaM deficient cells, underscoring its broad applicability. Together, these findings establish CTF-Ca as an effective 2D material for direct intracellular modulation of CaM, offers a promising new tool for regulating stem and progenitor cells fate.

Fermented ginseng by-products regulate calcium metabolism pathways, liver health, immune function and intestinal microbiota to improve eggshell quality and production performance in late-laying hens.

Background: Transfusion-dependent β-thalassemia (TDT) is commonly associated with vascular and endocrine complications, including hypoparathyroidism (HPT). Dysregulated angiogenesis and innate immune activation—reflected by vascular endothelial growth factor (VEGF) and pentraxin-3 (PTX3)—may contribute to endothelial dysfunction and altered calcium–phosphate balance. Objective: This study aimed to examine serum levels and mRNA expression of VEGF and PTX3 in patients with β-thalassemia major and to explore their relationship with endothelial injury, mineral disturbances, and HPT. Methodology: One hundred subjects were included: 50 healthy controls and 50 patients with β-thalassemia major (38 with normal parathyroid function and 12 with HPT). Serum VEGF and PTX3 were measured by ELISA, and gene expression was assessed using RT-qPCR. Correlation analyses and ROC curves were performed to evaluate associations and predictive performance. Results: Compared with controls, patients with β-thalassemia major had significantly elevated serum and mRNA expression levels of VEGF and PTX3 (p < 0.001). Within the patient group, those with HPT showed markedly higher levels than individuals with preserved parathyroid function (p < 0.001). VEGF and PTX3 correlated positively with serum phosphate and negatively with parathyroid hormone (p < 0.001). ROC analysis demonstrated good predictive accuracy for HPT: VEGF (AUC = 0.838; sensitivity 83%; specificity 74%) and PTX3 (AUC = 0.814; sensitivity 83%; specificity 71%). Conclusion: VEGF and PTX3 are significantly upregulated in β-thalassemia major, particularly in HPT, reflecting intertwined endothelial and innate immune activation with disordered mineral metabolism. They may serve as useful biomarkers of vascular and parathyroid dysfunction in TDT.

SPG11 models reveal lysosomal calcium regulation of neural progenitor proliferation.

The unique physicochemical properties of nanoparticles (NPs) have facilitated the development of targeted therapies for cardiovascular diseases (CVDs). According to World Health Organization estimates, CVDs are the predominant contributors to global mortality, accounting for approximately 17.9million deaths annually. Conventional treatments, including pharmacological interventions and surgical procedures, face significant barriers such as systemic toxicity due to non-targeted delivery, incomplete efficacy, and high financial burdens. Nanoscale innovations address these limitations through mechanisms such as targeted drug delivery and controlled release. Despite these advancements, concerns regarding NPs-induced cardiotoxicity remain unresolved. As nanomedicine advances rapidly, understanding NP functions within the cardiovascular system is essential for optimizing therapeutic outcomes in parallel to minimize unintended risks. Metal-based NPs, including gold, silver, and iron oxide, have demonstrated promising applications in cardiovascular imaging, regenerative therapy, and drug delivery; however, emerging evidence indicates their potential to induce oxidative stress, inflammatory responses, and endothelial dysfunction, contributing to atherosclerosis, myocardial injury, and arrhythmias. Inhaled and intravenously administered NPs exhibit dose-dependent toxicities that influence mitochondrial function and calcium homeostasis within cardiomyocytes. This review comprehensively analyzes in vitro and in vivo studies and notable clinical trials such as the NANOM-FIM trial. Furthermore, we discuss the role of specific antioxidants in cardioprotection and mitigating NPs-induced cardiotoxicity.

Denosumab is increasingly used to treat osteoporosis in patients with advanced kidney disease, but clinically significant disturbances in calcium homeostasis remain a major concern. We report a peritoneal dialysis (PD) case in which denosumab administration was followed by pronounced calcium fluctuations requiring medication management. A 56-year-old woman with end-stage kidney disease due to lupus nephritis, receiving prednisolone (5mg/day), had been on continuous ambulatory PD (1.5-L exchanges three times daily) for 5years. Baseline intact parathyroid hormone was 176pg/mL. Osteoporosis was confirmed by dual-energy X-ray absorptiometry (lumbar spine 68% and femoral neck 58% of the young adult mean [YAM]). Denosumab 60mg was administered, and BMD increased within 10months to 78% YAM at the lumbar spine and 77% YAM at the femoral neck (same facility, identical DXA equipment). To mitigate hypocalcemia, dialysate calcium was pre-emptively increased to two 3.5-mEq/L and one 2.5-mEq/L bags per day (albumin-corrected calcium 9.5mg/dL at dosing). Nonetheless, symptomatic hypocalcemia developed (nadir 7.8mg/dL on day 7), prompting escalation to three 3.5-mEq/L bags with intensified vitamin D therapy and calcium supplementation. Serum calcium then overshot, peaking at 13.8mg/dL on day 29; therapy was de-escalated and calcium stabilized. This case highlights that while daily dialysate calcium exposure in PD may buffer early hypocalcemia, concurrent escalation of dialysate calcium, vitamin D therapy, and calcium supplementation can precipitate overshoot hypercalcemia. Frequent monitoring and staged, stepwise prescription changes during the first month after denosumab are essential. Standardized PD-specific post-denosumab calcium management protocols are urgently needed.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder primarily affecting male children and resulting in progressive degeneration and attempted regeneration of muscle with replacement of myofibers by adipose and fibrotic tissue. DMD patients have mutations in the DMD gene encoding for the large cytoskeletal protein dystrophin, which plays an essential role in the dystrophin-glycoprotein complex (DGC) as a structural connector within cardiac and skeletal muscle. The absence of dystrophin and DGC proteins leads to increased membrane fragility, dysregulation of calcium homeostasis, oxidative damage in muscle cells, and finally, premature death of the patients. Rhabdomyosarcoma (RMS), a soft tissue sarcoma arising from subpopulations of muscle cells and their precursors, has previously been reported in DMD patients and mouse models of DMD. Here, we report a case series of RMS arising from skeletal muscles in a Dmd-mutated (Dmdmdx) rat model developed using transcription activator-like effector nucleases targeting exon 23 of the Dmd gene on a Sprague Dawley background. Subcutaneous firm masses were noted grossly in 8 male Dmdmdx rats aged 6 to 17 months. The histologic findings were consistent with a sarcoma of skeletal muscle, with a population of small round cells in addition to spindle-shaped cells and occasional large multinucleated cells. The neoplasms were immunoreactive for myogenin, MyoD1, and desmin. Histology and immunohistochemistry supported the diagnosis of RMS. This represents a potentially novel animal model of DMD-associated RMS.

Epigenetic regulation of neuronal calcium signaling during postnatal cortical development is critical for voluntary movement. Protein arginine methyltransferase 5 (PRMT5) acts as an epigenetic regulator that is involved in movement disorders, yet its underlying mechanism remains poorly understood. Here, we report that conditional knockout of Prmt5 in excitatory neurons (cKONex) during motor cortex development leads to severe hyperactivity and shortened lifespan in mice. Transcriptomics analysis reveals that PRMT5 deficiency upregulated Cacna1d expression without affecting its alternative splicing. We demonstrate that PRMT5 directly binds to the Cacna1d promoter, and represses its expression via catalyzing H4R3me2s histone methylation. Electrophysiological studies showed deletion of Prmt5 increased calcium influx and neuronal excitability, resulting from elevated L-type voltage-gated calcium channel (Cav1.3) activity. The enhanced calcium level further leads to oxidative phosphorylation defects in neurons. Importantly, administration of the L-type channel blocker, nimodipine, rescues hyperactivity and neuronal hyper-excitability in vivo, as well as markedly extends the lifespan of cKONex mice. Our findings establish a novel epigenetic mechanism wherein PRMT5-Cacna1d axis regulates neuronal excitability and motor development. These data provide new insights into the calcium channelopathy of movement disorders.

Dysfunctional adipocyte calcium handling is implicated in obesity and thermogenesis. Junctophilins (JPs) stabilize calcium microdomain junctions between the plasma membrane and endoplasmic reticulum, but whether JPs are required for adipocyte function is not known. We show that JP2 is enriched in thermogenic brown adipose tissue (BAT) relative to other fat depots and is downregulated under conditions of nutrient overload. Conditional knockdown of JP2 in adipocytes, and more selectively in BAT, exacerbates cold intolerance and susceptibility to diet induced obesity. Mechanistically, JP2-depleted brown adipocytes exhibit calcium handling dysfunction with elevated cytosolic calcium levels at baseline but diminished norepinephrine-induced calcium transients, reduced store-operated calcium entry. Basal cytosolic calcium overload accounts for an increase in calpain activation and ensuing downregulation of STIM1 and hormone-sensitive lipase in JP2-depleted cells. Furthermore, JP2 silencing in brown adipocytes reduced oxygen consumption rates and compromised mitochondrial structure and quality. Together, these findings demonstrate that JP2 is essential for normal calcium homeostasis in brown adipocytes and reveal a critical role for JP2 in thermogenesis and resistance to diet-induced metabolic dysregulation.