Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Background Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Methods Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Results Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-023-03614-y
Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients’ quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025124
Preeclampsia (PE) involves complex metabolic-inflammatory interactions, yet the mechanistic links among glycolysis, protein lactylation, and pyroptosis in placental pathogenesis remain undefined. In this study, we explore their tripartite relationship with PE development by combining bioinformatics analysis of PE-associated transcriptomes with experimental validation using placental tissues from PE patients and healthy controls. To elucidate the underlying mechanism, we utilize in vitro models involving hypoxic endothelial cell cultures, pharmacological glycolysis inhibition via 2-deoxyglucose, and genetic modulation of hexokinase 2 (HK2) expressions through siRNA silencing and plasmid-based overexpression. Molecular profiling is used to assess the expressions of key glycolytic enzymes, lactylation markers, and pyroptosis-related factors. Compared with control placental tissues, PE placental tissues present significantly higher expressions of glycolytic enzymes, elevated protein lactylation levels, and increased pyroptosis markers. Similarly, hypoxic endothelial cells exhibit coordinated upregulation of these three pathways. Notably, pharmacological glycolysis inhibition significantly reduces both lactylation and pyroptosis levels. Genetic experiments further demonstrate that HK2 silencing decreases glycolytic activity, subsequently attenuating lactylation and pyroptosis, whereas HK2 overexpression has opposite effects, underscoring its central regulatory role in this metabolic-inflammatory axis. Collectively, these findings indicate that HK2-mediated glycolysis drives placental vascular endothelial lactylation and pyroptosis, revealing a novel mechanistic pathway in PE pathophysiology.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024092
Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, driven by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. These effects are closely associated with the activation of SIRT1/FOXO3 signaling and the restoration of functional mitophagic flux. Our work highlights the SIRT1/FOXO3-mitophagy axis as a promising target for further investigation in the development of therapeutic strategies for IVDD.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.05.014
AIM: Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation, yet the spatial epigenetic and neuroimmune features within the skin remain poorly understood. This study aims to construct a spatial atlas of the neuroimmune and epigenetic microenvironment in psoriasis. METHODS: Formalin-fixed, paraffin-embedded skin tissue samples from five psoriasis patients and four healthy controls were stained with a 33-metal antibody panel targeting immune and epigenetic markers. Imaging data were processed to analyze immune cell composition, spatial relationships, and epigenetic marker distribution in psoriatic lesions. RESULTS: Analysis of over 163,000 cells from five psoriasis patients and four healthy controls revealed that psoriatic lesions have a more complex cellular composition than normal skin, including diverse immune subsets, endothelial cells, keratinocytes, and nerve fibers. Neighborhood analysis showed enrichment of multiple immune cells, such as CD14+ monocytes, CD4+/CD8+ T-lymphocytes (T cells), CD68+ macrophages, CD69+ tissue-resident memory T cells and CD20+ B-lymphocytes (B cells), and nerve fibers around keratinocytes. Notably, positive interactions were observed between cutaneous nerve fibers and specific immune cells (CD8+ T cells and CD68+ macrophages) as well as blood vessels. Additionally, histone H3 lysine 27 trimethylation (H3K27me3) modification was mapped across cell types and found in immune cells adjacent to keratinocytes. CONCLUSION: Imaging mass cytometry delineated the psoriatic microenvironment's multicellular structure integrating epigenetic and neuroimmune components, offering new insights into psoriasis pathogenesis.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025124
Preeclampsia (PE) is a multisystem syndrome affecting 2–8% of pregnancies, with placental dysfunction as a central driver. Metabolic dysregulation, particularly aberrant glycolysis, has been implicated in PE pathogenesis, but the mechanistic links among glycolysis, protein lactylation, and pyroptosis remain undefined. This study combined bioinformatics analysis of PE-associated transcriptomes with experimental validation using placental tissues from PE patients and healthy controls. In vitro models employed hypoxic endothelial cell cultures, pharmacological glycolysis inhibition via 2-deoxyglucose, and genetic modulation of hexokinase 2 (HK2) through siRNA silencing and plasmid-based overexpression. Molecular profiling assessed key glycolytic enzymes, lactylation markers, and pyroptosis-related factors. PE placental tissues exhibited significantly higher expressions of glycolytic enzymes, elevated protein lactylation, and increased pyroptosis markers compared to controls. Hypoxic endothelial cells showed coordinated upregulation of these pathways. Pharmacological glycolysis inhibition significantly reduced lactylation and pyroptosis. HK2 silencing decreased glycolytic activity, attenuating lactylation and pyroptosis, while HK2 overexpression had opposite effects, underscoring its central regulatory role. These findings indicate that HK2-mediated glycolysis drives placental vascular endothelial lactylation and pyroptosis, revealing a novel mechanistic pathway in PE pathophysiology and identifying HK2 as a potential therapeutic target.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781232251260
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.