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Pseudoexon activating by a deep intronic variant and phenotype variation in a Chinese family with dystrophinopathy.

Aberrant inclusion of pseudoexons (PE) in mature mRNA is a rare splicing defect contributing to Duchenne muscular dystrophy (DMD) pathogenes … r-complete loss of dystrophin. Functional assays further showed impaired myotube fusion and altered calcium signaling. This study underscores the diagnostic complexity of intronic DMD variants and provides evidence supporting the pathogenicity of c.6913-4037T>G.

PIEZO1 gain-of-function mutation drives cardiomyopathy by disrupting myocardial lipid homeostasis besides iron overload.

As a mechanosensitive channel, PIEZO1 translates mechanical stretching of cardiomyocytes into Ca2+ signaling, underpinning the Frank-Starling law. This mechanism contributes to compensatory responses in heart failure. However, the relationship between PIEZO1 mutations and the development of cardiomyopathy remains unclear. Acute heart failure complicated with severe myocardial iron deposition was identified in the 31-year-old male proband of PIEZO1D669Y variant. However, PIEZO1 gain-of-function (GOF) mutation D674Y mice and cardiomyocyte-specific Piezo1 overexpression disrupted cardiac function

Beyond energy: Mitochondrial control of platelet lifecycle through redox, calcium, and dynamics.

Platelet disorders, caused by quantitative deficiencies or functional impairments, significantly contribute to cardiovascular, neurological, and iatrogenic pathologies. Although platelets are indispensable for hemostasis, thrombosis, and immune responses, the molecular mechanisms governing their biogenesis from megakaryocytes (MKs) and subsequent functional regulation remain incompletely understood. Mitochondria, inherited from MK progenitors, are now recognized as central regulators of platelet physiology and pathology. Emerging evidence demonstrates that mitochondrial processes critically re

Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a+/- autism model mice.

Atypical sensory integration and contextual learning are common symptoms in autism spectrum disorder (ASD), but how sensory circuits are affected remains elusive. Here we focused on the early visual information processing, and performed in vivo two-photon calcium imaging and pupillometry of mice engaged in an implicit learning task in stable and volatile visual contexts. Wild-type (WT) mice show stimulus-specific contextual modulation of the visual responses in the superior colliculus (SC) and pupil dynamics, whereas SCN2A-haploinsufficient ASD-model mice exhibit abnormal modulation patterns.

In Silico Molecular Docking Analysis of Valproic Acid as an Inhibitor of Bruton's Tyrosine Kinase: Potential Drug Repurposing for Allergies.

Mast cells (MCs) participate in inflammation and pathological processes such as type I hypersensitivity. They can recognize type E immunoglobulins (IgE)-coupled allergens through the high-affinity receptors for IgE (FcεRI) membrane receptor, inducing the activation of a signaling pathway in which molecules such as spleen tyrosine kinase (SyK), Bruton's tyrosine kinase (BTK), and phospholipase Cy2 (PLCγ2) participate, promoting MC degranulation by promoting calcium mobilization. Valproic acid (VPA) selectively decreases PLCγ2 phosphorylation without impacting SyK kinase activity. Although BTK a

Targeting Metal Ion Homeostasis for Regulated Cell Death-Amplified Tumor Nanomedicine.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestr

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… Current research suggests that abnormal calcium signaling is intimately related to pathological processes such as neuronal loss in Alzheimer’s disease, cardiac injury caused by ischemia-reperfusion, and tumor treatment resistance ( Figure 8B ). 138 Understanding its molecular mechanisms has been a critical …

Developmental hepatotoxicity induced by flusilazole in zebrafish: Mechanistic insights into mitochondrial dysfunction, oxidative stress, ferroptosis, and regenerative impairment.

Flusilazole is a triazole-based fungicide that persists in various environments because of its high stability and solubility, raising concerns about its developmental and ecological impacts. Although numerous studies have reported flusilazole-induced toxicity, the specific effects and mechanisms of flusilazole-induced hepatotoxicity during development remain unclear. In this study, we examined the in vivo and in vitro toxicities in Danio rerio (zebrafish) and zebrafish-derived liver (ZFL) cells. Morphological changes in the liver and alterations in liver regeneration were evaluated using fabp1

Ethanol exposure during differentiation of human induced pluripotent stem cells reduces cardiomyocyte generation and alters metabolism.

Prenatal alcohol exposure increases the risk of congenital heart diseases (CHDs) by disrupting fetal development, yet the mechanisms underlying alcohol-induced cellular and molecular changes in human cardiogenesis remain unclear. This study investigates the effects of ethanol exposure on cardiomyocyte differentiation using human induced pluripotent stem cells (hiPSCs) as a model. Cardiomyocyte differentiation was induced using Wnt signaling molecules, and hiPSCs were treated with ethanol at concentrations of 17, 50, and 100 mM from day 0 to day 12. Ethanol treatment impaired cardiac differenti

Plasma Calmodulin as a Biomarker of Subclinical Cardiovascular Disease in Pediatric Chronic Kidney Disease.

BACKGROUND: Calmodulin is a calcium-signaling protein implicated in cardiac remodeling and could be released extracellularly. It was previously identified as differentially expressed in hypertensive pediatric chronic kidney disease (CKD). This study assessed plasma calmodulin as a cardiovascular disease (CVD) biomarker in pediatric CKD and compared it with traditional risk markers. METHODS: We conducted a cross-sectional study of 81 children with CKD aged 3-18 years. All underwent clinical assessments and echocardiography; 44 had carotid ultrasound, and 38 completed ambulatory blood pressure

Investigating the immunomodulatory effects of honeybee venom peptide apamin in Drosophila platforms.

Apamin, an 18-amino-acid honeybee venom peptide, although traditionally recognized for its neurotoxic effects, demonstrates potent antimicro … d with increased intestinal stem cell proliferation, midgut acidification, and enteroendocrine cell calcium signaling. Furthermore, apamin's antimicrobial function relies on specific peptidoglycan recognition proteins, particularly PGRP-LA and PGRP-SCs. Apamin expression alone is sufficient to restore the integrity of the gut barrier compromised by stressful condit …

Hypoxia, Psychedelics, and Terminal Lucidity: A Perspective on Neuroplasticity and Neuropsychiatric Disorders.

Hypoxia and psychedelics, despite their distinct origins, both induce altered states of consciousness and promote neuroplasticity, suggestin … ychedelics, near-death experiences, meditation, holotropic breathwork, or hypoxia therapiestrigger calcium signaling pathways that promote synaptogenesis and the formation of new neural circuits. Rather than restoring damaged connections, this process may enable functional rerouting, thereby supporting cognitive resilience and behavioral compensation in conditions …

The Role of Autophagy in the Mineralization Process of Bone and Dentin.

Autophagy is a cellular process that recycles intracellular macromolecules and degrades toxic cytoplasmic material to provide the cell with nutrients and facilitate survival. Although autophagy and its role in the differentiation of osteoblasts, osteoclasts, and odontoblasts has been described, the importance of autophagy during matrix mineralization remains unaddressed. This review aims to characterize the autophagy/matrix mineralization relationship and elucidate the significance of autophagy during matrix mineralization. During the mineralization process, autophagy is important for cell sur

C-JUN overexpressing CAR-T cells in acute myeloid leukemia: preclinical characterization and phase I trial.

Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines th

Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein.

Ulva prolifera, a type of green algae that can be consumed, was utilized in the production of an angiotensin-I converting enzyme (ACE) inhibitory peptide. The protein from the algae was isolated and subsequently hydrolyzed using a neutral protease. The resulting hydrolysate underwent several processes including Sephadex-G100 filtration chromatography, ultrafiltration, HPLC-Q-TOF-MS analysis, ADMET screening, UV spectrum detection test, molecular docking, and molecular dynamic simulation. Then, the ACE inhibitory peptide named KAF (IC50, 0.63 ± 0.26 µM) was identified. The effectiveness of this

Ano1 regulates embryo transport by modulating intracellular calcium levels in oviduct smooth muscle.

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i…

TRP channels: Role in neurodegenerative diseases and therapeutic targets.

TRP (Transient receptor potential) channels are integral membrane proteins consisting of a superfamily of cation channels that allow permeability of both monovalent and divalent cations. TRP channels are subdivided into six subfamilies: TRPC, TRPV, TRPM, TRPP, TRPML, and TRPA, and are expressed in almost every cell and tissue. TRPs play an instrumental role in the regulation of various physiological processes. TRP channels are extensively represented in brain tissues and are present in both prokaryotes and eukaryotes, exhibiting responses to several mechanisms, including physical, chemical, an

Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview.

Mitochondria play a vital role in the nervous system, as they are responsible for generating energy in the form of ATP and regulating cellular processes such as calcium (Ca2+) signaling and apoptosis. However, mitochondrial dysfunction can lead to oxidative stress (OS), inflammation, and cell death, which have been implicated in the pathogenesis of various neurological disorders. In this article, we review the main functions of mitochondria in the nervous system and explore the mechanisms related to mitochondrial dysfunction. We discuss the role of mitochondrial dysfunction in the development

Icariin negatively regulated lipopolysaccharide-induced inflammation and ameliorated the odontogenic activity of human dental pulp cells in vitro.

Alleviating inflammation and promoting dentine regeneration is critical for the healing of pulpitis. In this study, we investigated the anti-inflammatory, angiogenesis and odontogenesis function of icariin on Human dental pulp cells (HDPCs) under inflammatory state. Furthermore, the underlying mechanisms was also evaluated. Icariin attenuated the LPS-induced pro-inflammatory marker expression, such as interleukin-1β (IL-1β), IL-6 and IL-8. The immunoblotting and immunofluorescence staining results showed that icariin suppressed the inflammatory responses mediated by the protein kinase B (Akt)

A review of the pathophysiology and the role of ion channels on bronchial asthma.

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory res

Transcriptomic Differentiation of Phenotypes in Chronic Rhinosinusitis and Its Implications for Understanding the Underlying Mechanisms.

Chronic rhinosinusitis (CRS) is a multifaceted disease with variable clinical courses and outcomes. We aimed to determine CRS-associated nasal-tissue transcriptome in clinically well-characterized and phenotyped individuals, to gain a novel insight into the biological pathways of the disease. RNA-sequencing of tissue samples of patients with CRS with polyps (CRSwNP), without polyps (CRSsNP), and controls were performed. Characterization of differently expressed genes (DEGs) and functional and pathway analysis was undertaken. We identified 782 common CRS-associated nasal-tissue DEGs, while 375