Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04883-5
Background Pulmonary arterial hypertension (PAH) is a fatal condition characterized by progressive vascular remodeling in the pulmonary arteries, eventually leading to right heart failure and death. Dysregulated extracellular matrix (ECM) remodeling is central to PAH pathogenesis and represents a potential therapeutic target. Mesenchymal stromal cells (MSCs) have shown promise in preclinical studies; however, the optimal therapeutic window, dosing frequency, and mechanistic basis for their regulation of vascular ECM remain unclear. Methods We employed a monocrotaline (MCT)-induced rat model of PAH to evaluate different MSC treatment regimens, including early administration (day 1 post-MCT), delayed administration (days 7 and 14), and repeated dosing (days 1 and 11). Additionally, we combined in vivo and in vitro approaches to investigate how MSCs modulate the activation of pulmonary arterial adventitial fibroblasts (PAAFs) and influence ECM remodeling. Results Biodistribution studies indicated that MSC retention in lung tissue peaked within 24 h and gradually declined by day 21. A single early dose of MSCs (on day 1) significantly ameliorated PAH progression, increasing the 28-day survival rate, reducing right ventricular systolic pressure (RVSP), improving right ventricular function, and attenuating small pulmonary vascular remodeling, including reductions in medial thickening, excessive muscularization, and collagen deposition. Repeated MSC administration did not provide additional therapeutic benefit. Both in animal models and cell cultures, MSCs effectively suppressed PAAF activation and reduced ECM protein production. This anti-fibrotic effect was mediated via the SOCS3/STAT3 signaling pathway. Conclusions Early single-dose MSC therapy effectively alleviates PAH by suppressing PAAF activation and ECM remodeling through the SOCS3/STAT3 pathway, offering a potential therapeutic strategy for PAH.
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/s13287-025-04883-5
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by progressive vascular remodeling, leading to right heart failure. Dysregulated extracellular matrix (ECM) remodeling is central to PAH pathogenesis. Mesenchymal stromal cells (MSCs) have shown promise, but optimal dosing and mechanisms remain unclear. In a monocrotaline (MCT)-induced rat model, we evaluated early (day 1), delayed (days 7 and 14), and repeated (days 1 and 11) MSC administration. Biodistribution showed peak lung retention at 24 h, declining by day 21. A single early dose significantly improved 28-day survival, reduced right ventricular systolic pressure (RVSP), improved right ventricular function, and attenuated vascular remodeling, including medial thickening, muscularization, and collagen deposition. Repeated dosing provided no additive benefit. MSCs suppressed pulmonary arterial adventitial fibroblast (PAAF) activation and ECM protein production in vivo and in vitro. Mechanistically, MSCs upregulated SOCS3 and inhibited STAT3 signaling. These findings support early single-dose MSC therapy for PAH.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21320
BACKGROUND: Xanthohumol is a natural polyphenol that exhibits biological activities such as antioxidant and anti-inflammatory properties. Recently, it has been found to potentially improve lipid metabolism disorders. As an aerobic exercise, swimming can effectively regulate body energy metabolism and reduce hepatic fat accumulation. However, the intervention effect and mechanism of their combined application on metabolic associated fatty liver disease remain unclear. OBJECTIVE: To investigate the effect of xanthohumol combined with swimming on the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2 in rats with metabolic associated fatty liver disease. METHODS: Rats were randomly divided into seven groups: control group, model group, exercise group, low-, medium-, and high-dose xanthohumol, and combination groups, with 12 rats in each group. The rats in control group were fed with normal feed, while the rats in other groups were used to prepare metabolic associated fatty liver disease models. Rats in the exercise and combination groups received swimming training once a day, 6 days per week, for a total of 8 weeks. Rats in other groups were raised quietly. Rats in the low-, medium-, and high-dose xanthohumol groups were intragastrically administered 2 mL of 25, 50, and 100 mg/(kg·d) xanthohumol, respectively; rats in the combination group were intragastrically administered 2 mL of 100 mg/(kg·d) xanthohumol while undergoing swimming training; other groups were intragastrically administered 2 mL of 0.3% sodium carboxymethyl cellulose, for a total of 8 weeks. After treatment, serum alanine aminotransferase, aspartate aminotransferase, and free fatty acid levels were measured; hepatic lipid accumulation was observed by hematoxylin-eosin staining; hepatic malondialdehyde and reduced glutathione levels were detected according to kit instructions; hepatic ferrous ion content was measured by microassay; Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, and glutathione peroxidase 4 in liver tissue; RT-qPCR was used to detect the mRNA levels of ferroptosis-related genes (glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, ferroportin 1, and cationic transport regulator-like protein 1). RESULTS AND CONCLUSION: Compared with the exercise group and high-dose xanthohumol group, the combination group showed lower serum alanine aminotransferase, aspartate aminotransferase, and free fatty acid levels, improved liver morphology, decreased hepatic malondialdehyde level, increased reduced glutathione level, decreased hepatic ferrous ion content, increased protein expression of nuclear factor erythroid 2-related factor 2 (nuclear) and glutathione peroxidase 4, decreased protein expression of Kelch-like ECH-associated protein 1, increased mRNA levels of glutathione peroxidase 4, solute carrier family 7 member 11, ferritin heavy chain 1, and ferroportin 1, and decreased mRNA level of cationic transport regulator-like protein 1 (P < 0.05). These findings suggest that xanthohumol combined with swimming may improve hepatic injury in rats with metabolic associated fatty liver disease by regulating the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21429
BACKGROUND: The etiology of Alzheimer’s disease is diverse and its pathogenesis remains complex and incompletely understood. In recent years, non-coding RNAs have been demonstrated to play a key role in the regulation of amyloid-β abnormal deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, and synaptic damage, offering new perspectives for elucidating mechanisms underlying diseases and development of drugs. Additionally, by regulating non-coding RNA networks, traditional Chinese medicine exhibits the advantages of multi-pathway intervention. OBJECTIVE: To review recent studies on the role of regulatory non-coding RNAs and transfer RNAs in the pathological mechanisms of Alzheimer’s disease, summarize the current status of traditional Chinese medicine monomers, compound formulas, and acupuncture in regulating different non-coding RNAs to exert anti-Alzheimer’s disease effects, and provide theoretical basis and direction reference for future optimization of clinical treatment strategies and development of novel drugs. METHODS: Using Chinese and English search terms including 'non-coding RNA, microRNA, long non-coding RNA, circular RNA, transfer RNA, Alzheimer’s disease, traditional Chinese medicine', relevant literature published from January 2015 to July 2025 was retrieved from CNKI and PubMed databases. According to inclusion and exclusion criteria, 101 articles were finally included for review. RESULTS AND CONCLUSION: (1) The occurrence and development of Alzheimer’s disease originate from a multifactorial interrelated pathological network, mainly including amyloid-β deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, oxidative stress, synaptic structural and functional abnormalities, and calcium homeostasis imbalance, which can also interweave and synergistically promote disease progression. (2) Various regulatory non-coding RNAs such as microRNAs, long non-coding RNAs, circular RNAs, and transfer RNAs among housekeeping non-coding RNAs can regulate the above pathological processes at different levels, thereby affecting disease progression. (3) Many active components of traditional Chinese medicine monomers such as berberine, catalpol, Panax notoginseng saponins, ginsenoside Rg1, β-asarone, triptolide, and tanshinone IIA; traditional Chinese medicine compound formulas such as Anshen Dingzhi Formula, Tiaoxin Formula, Bushen Tiansui Formula; and acupuncture and moxibustion can upregulate or downregulate specific non-coding RNAs to intervene in multiple pathological links of Alzheimer’s disease, exert neuroprotective effects, and delay the occurrence and development of the disease.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21446
BACKGROUND: Currently, many oral periodontal bone substitute materials suffer from drawbacks such as poor biomechanical properties and degradation characteristics. Using composite periodontal bone substitute materials can compensate for the shortcomings of single materials and better achieve the construction of 'periodontal bone tissue engineering constructs'. OBJECTIVE: To prepare beta-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials by freeze-drying method and characterize their properties. METHODS: Polyvinyl alcohol hydrogels with a concentration of 15% were prepared. Different masses of beta-tricalcium phosphate were added to the polyvinyl alcohol hydrogels, and after freeze-drying, 10%, 20%, and 30% beta-tricalcium phosphate/polyvinyl alcohol composite materials were obtained. Similarly, different masses of hydroxyapatite were added to polyvinyl alcohol hydrogels, and after freeze-drying, 10%, 20%, and 30% hydroxyapatite/polyvinyl alcohol composite materials were obtained. The properties of each composite material were characterized using scanning electron microscopy, X-ray energy dispersive spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy. RESULTS AND CONCLUSION: (1) Scanning electron microscopy and X-ray energy dispersive spectroscopy analysis showed that beta-tricalcium phosphate and hydroxyapatite particles were successfully combined with polyvinyl alcohol hydrogel to form stable composite materials. With increasing concentration of beta-tricalcium phosphate or hydroxyapatite, the aggregation degree of particles in the composite materials increased and the porosity decreased. The main elements in each composite material included Ca, P, C, and O. (2) X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy results showed that no new bending vibration peaks, stretching vibration peaks, or characteristic peaks appeared in the beta-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials. These results indicate that the beta-tricalcium phosphate/polyvinyl alcohol and hydroxyapatite/polyvinyl alcohol composite materials prepared by freeze-drying have stable properties.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21444
BACKGROUND: Icariin has the dual activity of promoting bone formation and inhibiting bone resorption, but its clinical application is plagued by low bioavailability, difficulty in controlling dosage, and a high risk of adverse reactions. OBJECTIVE: To prepare a three-dimensional scaffold containing icariin sustained-release microspheres and characterize their osteogenic activity in vitro. METHODS: A silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold (SF/CS/nHA scaffold), icariin sustained-release microspheres, and a silk fibroin/chitosan/nanohydroxyapatite three-dimensional scaffold loaded with icariin sustained-release microspheres (SF/CS/nHA-ICA scaffold) were prepared. The drug loading efficiency, encapsulation efficiency, and in vitro drug release of the icariin sustained-release microspheres were characterized. The pore size, porosity, water absorption expansion rate, and hot water dissolution rate of the two scaffolds were measured. Rabbit bone marrow mesenchymal stem cells (or human rheumatoid arthritis fibroblast-like synoviocytes) were seeded on SF/CS/nHA and SF/CS/nHA-ICA scaffolds, with cells cultured alone as controls. Cell adhesion was observed by scanning electron microscopy. Cell proliferation and viability were assessed by CCK-8 assay, live/dead staining, and F-actin staining. The mRNA and protein expression of Runx-2, osteocalcin, and type I collagen in bone marrow mesenchymal stem cells were detected by RT-qPCR and western blot. RESULTS AND CONCLUSION: (1) The drug loading efficiency and encapsulation efficiency of icariin sustained-release microspheres were (29.38±0.04)% and (52.01±0.09)%, respectively, and the microspheres could sustainably release icariin for more than 90 days in vitro. (2) Scanning electron microscopy showed a honeycomb-like porous structure with interconnected pores in both scaffolds. There were no significant differences in pore size, porosity, water absorption expansion rate, or total hot water dissolution rate between the two groups (P > 0.05). (3) Scanning electron microscopy showed that both cell types adhered tightly to the scaffold surface and pores, with more extended pseudopodia on the SF/CS/nHA-ICA scaffold. CCK-8 assay, live/dead staining, and F-actin staining showed that compared with the control and SF/CS/nHA groups, the SF/CS/nHA-ICA scaffold promoted the proliferation and viability of rabbit bone marrow mesenchymal stem cells, while inhibiting the proliferation and viability of human rheumatoid arthritis fibroblast-like synoviocytes. (4) RT-qPCR and western blot showed that compared with the control and SF/CS/nHA groups, the mRNA and protein expression of Runx-2, osteocalcin, and type I collagen were increased in the SF/CS/nHA-ICA group (P < 0.05). (5) These results indicate that the icariin sustained-release microsphere three-dimensional scaffold has good cytocompatibility, and in vitro osteogenic and anti-inflammatory effects.
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.