Cell Biochemistry and Function最新文献

Botryosphaeran is an exocellular (1 → 3)(1 → 6)-β-d-glucan that promotes significant metabolic effects in male rats, as antiobesogenic and hypoglycemic effects. This study aimed to investigate its metabolic effects in female Wistar rats subjected to a high-fat high-sucrose diet. Obesity induction resulted in increased body weight, accumulation of adipose tissue, glucose intolerance, insulin resistance, hepatomegaly and high levels of TBARS (oxidative stress marker) in the liver, compared with the controls; all differences were statistically significant (p ˂0.05). Treatment with botryosphaeran (12 mg/kg/day; 15 days) significantly reduced the weight gain (p ˂0.01), the retroperitoneal adipose tissue (−29.7%, p ˂0.05), and corrected glucose intolerance with a 8.32% reduction in the area under the curve (AUC, p ˂0.05), relative to untreated obese rats. Furthermore, botryosphaeran reduced the levels of TBARS (−45.4%, p ˂0.05) in liver, reducing oxidative stress. Additionally, no differences were observed in the liver for protein carbonyls, superoxide dismutase, catalase, glutathione peroxidase, and ascorbic acid. In conclusion, botryosphaeran was observed to promote a significant antiobesogenic effect, promoting an expressive loss in body-weight, reduction of adipose tissue, correction of glucose intolerance and promoting an antioxidant effect in the female rats.

Joint inflammation and structural damage in spondyloarthritis (SpA) are not fully explained by known immune mechanisms. While mitochondrial dysfunction has been implicated in other rheumatic diseases, such as rheumatoid arthritis and lupus, its role in SpA remains poorly understood. Male DBA/1 mice with spontaneous arthritis (SpAD) and healthy BALB/c mice were compared to assess mitochondrial alterations in joint tissues, isolated mitochondria and cultured fibroblast-like synoviocytes (FLS). Analyses focused on mitochondrial dynamics (fission and fusion) and turnover (biogenesis and mitophagy), bioenergetic function, oxidative stress, and transcriptomic changes associated with mitochondrial function. SpAD induced a coordinated mitochondrial dysfunction in joint tissues characterized by increased fission (Drp1), reduced fusion (Mfn2), and dysregulated turnover processes with elevated mitophagy (PINK1) and biogenesis (PGC-1α). This imbalance led to dysregulation mitochondrial complexes activity, reduced ATP production, and a pronounced increase in oxidative stress. The latter was evidenced by decreased catalase and glutathione peroxidase (Gpx) activity, elevated superoxide dismutase (SOD) activity, and accumulation of 4 hydroxynonenal (4-HNE), highlighting a shift toward a chronic pro-oxidative environment. Similar gene expression changes were observed in cultured FLS. Transcriptomic analysis identified 6,673 differentially expressed genes, including 139 related to mitochondrial function, which reinforces the central role of mitochondrial dysregulation in SpAD pathophysiology. This study is the first to comprehensively characterize mitochondrial dysfunction in a murine model of SpA, identifying it as a potential driver of joint damage. Targeting mitochondrial pathways may offer novel strategies for disease modification in spondyloarthritis.

Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in preterm infants, characterized by dysregulated macrophage polarization and oxidative stress. While mesenchymal stem cell-derived exosomes (MSC-Exos) have shown protective effects against BPD, the role of exosomes derived from hypoxia-preconditioned MSCs (Hypo-Exos) remains unclear. This study aimed to investigate whether Hypo-Exos alleviate BPD by modulating alveolar macrophage (AM) polarization and oxidative stress via the mitochondrial transporter SLC25A3. We utilized in vitro models of LPS-induced M1 polarization and H₂O₂-induced oxidative stress in AMs, as well as an in vivo rat model of BPD induced by intermittent hypoxia. Our data demonstrate that hypoxic preconditioning enhanced exosome secretion from MSCs. Furthermore, hypoxic preconditioning promoted the packaging of SLC25A3 into these exosomes. Hypo-Exos significantly suppressed M1 polarization, reduced oxidative stress, and ameliorated lung injury and dysfunction in BPD rats. Silencing SLC25A3 in MSCs abolished these protective effects. Mechanistically, SLC25A3 interacted with PTEN, leading to inhibition of PTEN expression and activation of the PI3K/AKT signaling pathway. Overexpression of PTEN reversed the beneficial effects of SLC25A3 on macrophage polarization and oxidative stress. These findings reveal that Hypo-Exos deliver SLC25A3 to AMs, thereby downregulating PTEN, activating PI3K/AKT signaling, promoting M2 polarization, attenuating oxidative damage, and ultimately mitigating BPD progression. This study provides important mechanistic insights and suggests potential therapeutic avenues for exosome-based treatment of BPD.

Advanced oxidation protein products (AOPP) are generated from oxidation that is mainly promoted by the action of hypochlorous acid (HOCl) on proteins, such as albumin. However, new pathways and targets associated with AOPP formation must be identified and thoroughly evaluated. Non-enzymatic post-translational modifications (NEPTMs), such as protein carbamylation, are relevant in chronic kidney disease and other inflammation-related processes. Therefore, the aim of this study was to determine whether incubating HOCl with gamma globulins promotes AOPP formation and whether potassium cyanate (KOCN)-induced carbamylation of albumin and gamma globulins is a new pathway for AOPP formation. Solutions comprising 451 and 86 μM of albumin and gamma globulins, respectively, were incubated with HOCl (2 and 4 mM) and KOCN (150 nM and 150 μM) for 30 min, and then AOPP formation and the concentrations of protein carbonyl and homocitrulline were monitored. Notably, HOCl-induced oxidation of gamma globulins and albumin increased AOPP production. Gamma globulins also generated a higher amount of AOPP than albumin. Exposure of albumin and gamma globulins to HOCl resulted in a significant increase in protein carbonyl content, whereas exposure to KOCN led to a significant increase in homocitrulline. These findings suggest that gamma globulins are a new target of AOPP and KOCN participates in an alternate pathway of AOPP formation, thereby providing a new hypothesis regarding the pathways of AOPP formation during inflammation.

Triple-negative breast cancer (TNBC) signifies an enormous risk to women's health globally. TNBC is characterized by its aggressive nature, resistance to existing therapies, and poor prognosis. Understanding the molecular pathogenesis of breast cancer is crucial for identifying screening markers and therapeutic targets. In order to find commonly expressed differentially expressed genes (DEGs) in a variety of TNBC cell lines treated with docetaxel (GSE70690), paclitaxel (GSE86839), doxorubicin (GSE202536), and cisplatin (GSE77515), as well as untreated TNBC cell lines (GSE38959), bioinformatics approaches were used. The R software was utilized, and the cutoff criteria for the analysis were set at p < 0.01 and |log2FC| > ±1. A Venn diagram was used to identify the shared DEGs across TNBC cell lines treated with and without the targeted chemotherapeutic drugs. The DEGs that were found were analyzed to determine their involvement in specific biological processes and pathways using gene ontology and Reactome pathway enrichment analysis. Protein–protein interactions (PPI) were subsequently established, and the hub genes were discovered. Through data analysis, the study identified a set of DEGs associated with the response to chemotherapy drugs in TNBC. The GO analysis revealed that the DEGs identified were primarily associated with cell cycle regulation, cell population proliferation, and microtubule-related functions. Reactome pathway analysis showed enrichment in cell cycle processes, mitotic phases, and DNA damage checkpoints. Hub genes, such as CDK2, PLK4, and BIRC5, were identified based on their high degree of connectivity in the PPI network. The identified DEGs and pathways in this study shed light on possible therapeutic targets and reducing drug resistance. These findings contribute to the development of personalized and targeted therapies for TNBC, ultimately leading to improved patient outcomes.

The cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway has emerged as a critical cytosolic DNA-sensing mechanism that orchestrates innate immune activation in response to cellular stress. In the central nervous system (CNS), this pathway demonstrates highly context-specific and cell-type-dependent functions, ranging from promoting neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), to modulating immune surveillance and therapeutic responsiveness in glioma. This review systematically delineates the molecular mechanisms, activation patterns, and regulatory networks of cGAS–STING signaling in the CNS. We highlight its dualistic roles in both inflammatory exacerbation and antitumor immunity, and further discuss recent advances in therapeutic strategies, including pharmacological modulators, blood–brain barrier (BBB)-penetrating delivery platforms, and nanotechnology-based precision interventions. Finally, we propose future directions focused on decoding tissue-specific immunodynamics and developing spatiotemporally controlled, multiorgan immunoregulatory frameworks. Together, this review underscores cGAS–STING as a promising therapeutic axis in the evolving landscape of neuroimmunology.

Atherosclerosis (AS) is a chronic cardiovascular disorder characterized by lipid accumulation and the formation of atherosclerotic plaques on the arterial walls, leading to arterial stenosis and serving as a principal pathological feature. This condition significantly contributes to elevated mortality and disability rates globally. The NRF2 pathway plays a pivotal role in the pathogenesis of AS. It governs a variety of physiological and pathophysiological processes including lipid homeostasis, foam cell formation, macrophage polarization, redox balance and inflammation, which are integral to the progression of the disease. This review highlights the influence of NRF2 on AS by discussing its upstream regulator hydrogen sulfide (H₂S) and key downstream effectors such as the NLRP3 inflammasome, microRNAs, and heme oxygenase-1.

To explore the effects of a collagen-binding domains-bone morphogenetic protein 2 (CBD-BMP-2) scaffold on repairing cartilage defects. A chitosan-collagen scaffold was prepared and its physicochemical properties were evaluated. A plasmid encoding the CBD and BMP-2 was constructed, a CBD-BMP-2 composite scaffold was prepared, and the controlled release of BMP-2 was assessed in vitro. Knee cartilage defect model rabbits were divided into the control, CBD, and CBD-BMP-2 groups (n = 9). Gross observation, MRI, staining, and IHC were performed to evaluate the cartilage repair outcomes. CBD-BMP-2 composite scaffold provided sufficient support and promoting cell attachment and proliferation. It consistently released BMP-2 for over 30 days in vitro. It significantly enhanced cartilage regeneration and repair. After surgery, cartilage growth in the CBD-BMP-2 group was superior to the control and CBD groups. The CBD-BMP-2 group demonstrated better coverage of new cartilage tissue. In the CBD-BMP-2 group, new cartilage tissue was tightly structured and cells were neatly arranged, and there were a rich cartilage matrix and dense collagen fibers. Type II collagen expression was significantly increased in the CBD-BMP-2 group. CBD-BMP-2 composite scaffold has excellent physicochemical properties and controlled-release functionality, providing superior repair effects for rabbit knee joint cartilage defects.