Exploration of anti-osteoporotic peptides from Moringa oleifera leaf proteins by network pharmacology, molecular docking, molecular dynamics and cellular assay analyses

Journal of Functional Foods, Год журнала: 2024, Номер 116, С. 106144 - 106144

Опубликована: Март 24, 2024

Moringa oleifera leaf peptide, which is a plant-derived bioactive exhibits several advantages, including safety, high efficiency and nontoxic side effects. The goal of this study was to identify representative antiosteoporotic peptides from proteins determine their regulatory mechanisms using network pharmacology, molecular docking dynamics. following core targets were screened by pharmacology: SRC, MAPK1, JUN STAT3. Through docking, DPYLGK identified as active peptide the protein, SRC determined be potential primary target. Molecular dynamics revealed intermolecular mechanism SRC. Cellular assays showed that promotes bone formation inhibits resorption. These findings demonstrated an anti-osteoporotic with dual effects will aid in development functional foods prevent osteoporosis.

Язык: Английский

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Macrophage lysate-derived cytokine network combined with silk fibroin hydrogel promotes diabetic vascularized bone regeneration

Chemical Engineering Journal, Год журнала: 2024, Номер 490, С. 151892 - 151892

Опубликована: Май 3, 2024

Cell-based therapies are used extensively in tissue engineering because of their great biosafety and diverse biological functions. Among them, macrophage lysate provides a comprehensive rich network cytokines to modulate the local immune microenvironment. However, effective strategies for lysate-based biomaterials with immune-regulatory function still lacking. In this study, we engineered silk fibroin hydrogel loaded THP-1 whole-cell regulate microenvironment promote vascularized bone regeneration diabetic defects. Specifically, by modulating expression pattern key enzyme energy metabolism (mitochondrial phosphoenolpyruvate carboxykinase, PCK2) cells, generated enriched anti-inflammatory factors. This facilitated osteogenic differentiation BMSCs angiogenesis HUVECs vitro, incorporating immunomodulatory into enhanced diabetes. Mechanistically, revealed that PCK2 activated nuclear factor-kappa B (NF-κB) signaling pathway macrophages using proteomic profiling. research new insights design cell-derived biomaterials, aiming improve therapeutic outcomes pathological

Язык: Английский

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Interruption of mitochondrial symbiosis is associated with the development of osteoporosis

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Фев. 3, 2025

Mitochondria maintain bacterial traits because of their endosymbiotic origins, yet the host cell recognizes them as non-threatening since organelles are compartmentalized. Nevertheless, controlled release mitochondrial components into cytoplasm can initiate death, activate innate immunity, and provoke inflammation. This selective interruption endosymbiosis early 2 billion years ago allowed mitochondria to become intracellular signaling hubs. Recent studies have found that symbiosis may be closely related occurrence various diseases, especially osteoporosis (OP). OP is a systemic bone disease characterized by reduced mass, impaired microstructure, elevated fragility, susceptibility fracture. The intra-mitochondrial affects energy metabolism cells, leads imbalance formation absorption, promotes osteoporosis. In this paper, we reviewed mechanism intersymbiosis in OP, discussed relationship between marrow mesenchymal stem osteoblasts osteoclasts, well inheritance adaptation evolutionary process, prospected future research direction provide new ideas for clinical treatment.

Язык: Английский

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Identification of endoplasmic reticulum stress and mitochondrial dysfunction related biomarkers in osteoporosis

Hereditas, Год журнала: 2025, Номер 162(1)

Опубликована: Фев. 14, 2025

Abstract Background Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction (MD) involved in bone metabolism disorders. However, the particular mechanisms of ERS MD related genes (ERS&MDRGs) osteoporosis (OP) have not been elucidated. In present study, biomarkers to OP were identified. Methods Differentially expressed (DEGs) obtained based on GEO dataset. ERS&MDRGs derived from Genecard database. Initially, ERS&MD DEGs (ERS&MDRDEGs) by overlapping ERS&MDRGs. The key module was screened WGCNA. intersection ERS&MDRDEGs machine learning obtain genes. Then, receiver operating characteristic curve (ROC) drawn calculated diagnostic accuracy ssGSEA Cibersort algorithms performed analyze immune cell infiltration. miRNA-mRNA-TF network draw cytoscape software. Moleculaer docking DGIdb database employed for screening potential drugs. Finally, expression verified qRT-PCR. Results 122 preliminary screening. mainly enriched lipid metabolism, calcium ion transport, ossification. 5 identified, including AAAS , ESR1 SLC12A2 TAF15 VAMP2 . Immune infiltration analysis showed monocyte macrophage different between control groups. regulatory indicated has-miR-625-5p, has-miR-296-3p, CTCT EP300 as targets. 2 small molecule drugs, namely bumetanide elacestrant screened. higher, lower than group. Conclusion This research identified Bumetanide These findings provided valuable insights into pathophysiology development new therapeutic strategies.

Язык: Английский

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Mitochondrial Dysfunction and Its Potential Molecular Interplay in Hypermobile Ehlers–Danlos Syndrome: A Scoping Review Bridging Cellular Energetics and Genetic Pathways

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(2), С. 134 - 134

Опубликована: Фев. 19, 2025

Hypermobile Ehlers–Danlos Syndrome (hEDS) is a hereditary connective tissue disorder characterized by joint hypermobility, skin hyperextensibility, and systemic manifestations such as chronic fatigue, gastrointestinal dysfunction, neurological symptoms. Unlike other EDS subtypes with known genetic mutations, hEDS lacks definitive markers, suggesting multifactorial etiology involving both mitochondrial dysfunction non-mitochondrial pathways. This scoping review, conducted in accordance the PRISMA-ScR guidelines, highlights potential unifying mechanism pathophysiology. Impaired oxidative phosphorylation (OXPHOS), elevated reactive oxygen species (ROS) levels, calcium dysregulation disrupt cellular energetics extracellular matrix (ECM) homeostasis, contributing to hallmark features of hEDS. We reviewed candidate genes associated ECM remodeling, signaling pathways, immune regulation. Protein–protein interaction (PPI) network analyses revealed interconnected pathways linking these genes. Comparative insights from Fabry disease fragile X premutation carriers underscore shared mechanisms RNA toxicity, metalloproteinases (MMP) activation, degradation. These findings may suggest that amplifies through its interplay molecular By integrating perspectives, this review provides framework for understanding pathogenesis while highlighting latent avenues future research into basis. Understanding role not only sheds light on complex but also opens new paths targeted interventions.

Язык: Английский

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SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics

The Journal of Cell Biology, Год журнала: 2025, Номер 224(5)

Опубликована: Март 7, 2025

We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy OXPHOS machinery components. In control conditions, localizes to early endocytic compartments in PtdIns3P-dependent manner and modulates trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking late structures containing selected mitochondrial proteins, including COX-IV SAMM50, autophagy proteins SQSTM1/p62 LC3B. The turnover was enhanced SNX10-depleted cells, corresponding reduced respiration citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show levels Cox-IV, well elevated ROS ROS-mediated cell death brain, demonstrating vivo relevance SNX10-mediated modulation bioenergetics.

Язык: Английский

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Protein succinylome analysis identifies citrate synthase as a central regulator of osteoclast metabolic activity

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Tumour necrosis factor ligand superfamily member 11 (TNFSF11; RANKL) and macrophage colony-stimulating 1 receptor (M-CSF) differentiate macrophages into osteoclasts. This process is characterised by changes in metabolic activity that support energy-consuming processes. Treatment with RANKL triggers a phenotype of accelerated metabolism enhanced glycolysis an initial disruption the tricarboxylic acid cycle (TCA) through increased expression enzyme aconitate decarboxylase (ACOD1), which results upregulation intracellular succinate levels. Succinate then causes post-translational succinylation lysine residues. ACOD1 as inducer protein desuccinylase NAD-dependent deacylase sirtuin-5, mitochondrial (SIRT5) are regulated differentially, initially high decreases towards end differentiation, whereas SIRT5 levels increase. To mimic effect succinylation, diethyl or inhibitor was added during reduced formation large osteoclasts, showing its relevance for osteoclastogenesis. identify succinylated proteins, we used immunoaffinity-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. Most proteins were enzymes. Citrate synthase (CS), catalysing first reaction TCA cycle, showed notable difference before after stimulation, detected exclusively stimulated cells. Immunoprecipitation assays confirmed CS succinylation. Using whole cell extracts, observed treatment decreased concentration-dependent manner. suggests could be critical context energy production osteoclastogenesis modulates differentiation program

Язык: Английский

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Engineered Extracellular Vesicles Derived from Juvenile Mice Enhance Mitochondrial Function in the Aging Bone Microenvironment and Achieve Rejuvenation

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Aging-related bone degeneration and impaired healing capacity remain significant challenges in regenerative medicine, necessitating innovative, efficient, targeted strategies to restore health. Here, we engineered extracellular vesicles (EVs) derived from the serum of pretreated juvenile mice, with goals reversing aging, enhancing osteogenic potential, increasing bioavailability rejuvenate aging environment. First, established models representing different phases identify EV type highest potential for improving microenvironment older individuals. Second, employed DSS6 targeting enhance biological effects selected EVs vivo. The effectively repair sites promoted fracture more than unmodified mice. RNA sequencing revealed that translocase outer mitochondrial membrane 7 (Tomm7) is crucial underlying mechanism. Silencing Tomm7 significantly diminished positive regulatory EVs. Specifically, may function cells by activating Tomm7-mediated Pink1/Parkin mitophagy pathway, promoting stemness recovery marrow stromal (BMSCs) adverse conditions microenvironment. Overall, developed mice offer an alternative approach treating bones. identified mechanisms provide a valuable reference precision treatment bones future.

Язык: Английский

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Antioxidant scaffolds for enhanced bone regeneration: recent advances and challenges

BioMedical Engineering OnLine, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 8, 2025

Язык: Английский

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Cuproptosis and its potential role in musculoskeletal disease

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 11, 2025

Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, plays critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, mitochondrial dysfunction. Distinct other death mechanisms, cuproptosis is characterized by ion binding to acetylated respiratory chain proteins, leading pathogenic protein aggregation, iron-sulfur cluster depletion, cellular collapse. Emerging evidence underscores aberrant accumulation resultant proteotoxic stress as pivotal contributors the pathogenesis musculoskeletal pathologies, osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, biofilm-associated orthopedic infections. Understanding spatiotemporal regulation may provide novel opportunities for advancing diagnostic therapeutic approaches medicine. This review synthesizes current insights into molecular mechanisms cuproptosis, its diseases, potential biomarker-driven interventions.

Язык: Английский

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