Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03821-1
Background Intrauterine adhesions (IUAs) jeopardise uterine function in women, which is a great challenge in the clinic. Previous studies have shown that endometrial perivascular cells (En-PSCs) can improve the healing of scarred uteri and that hydroxysafflor yellow A (HSYA) promotes angiogenesis. The purpose of this study was to observe whether the combination of En-PSCs with HSYA could improve the blood supply and fertility in the rat uterus after full-thickness injury. Methods En-PSCs were sorted by flow cytometry, and the effect of HSYA on the proliferation and angiogenesis of the En-PSCs was detected using CCK-8 and tube formation assays. Based on a previously reported rat IUA model, the rat uteri were sham-operated, spontaneously regenerated, or treated with collagen-loaded PBS, collagen-loaded HSYA, collagen-loaded En-PSCs, or collagen-loaded En-PSCs with HSYA, and then collected at both 30 and 90 days postsurgery. HE staining and Masson staining were used to evaluate uterine structure and collagen fibre deposition, and immunohistochemical staining for α-SMA and vWF was used to evaluate myometrial regeneration and neovascularization in each group. A fertility assay was performed to detect the recovery of pregnancy function in each group. RNA-seq was performed to determine the potential mechanism underlying En-PSCs/HSYA treatment. Immunofluorescence, tube formation assays, and Western blot were used to validate the molecular mechanism involved. Results The transplantation of Collagen/En-PSCs/HSYA markedly promoted uterine repair in rats with full-thickness injury by reducing fibrosis, increasing endometrial thickness, regenerating myometrium, promoting angiogenesis, and facilitated live births. RNA sequencing results suggested that En-PSCs/HSYA activated the NRG1/ErbB4 signaling pathway. In vitro tube formation experiments revealed that the addition of an ErbB inhibitor diminished the tube formation ability of cocultured En-PSCs and HUVECs. Western blot results further showed that elevated levels of NRG1 and ErbB4 proteins were detected in the Collagen/En-PSCs/HSYA group compared to the Collagen/En-PSCs group. These collective results suggested that the beneficial effects of the transplantation of Collagen/En-PSCs/HSYA might be attributed to the modulation of the NRG1/ErbB4 signaling pathway. Conclusions The combination of En-PSCs/HSYA facilitated morphological and functional repair in rats with full-thickness uterine injury and may promote endometrial angiogenesis by regulating the NRG1/ErbB4 signaling pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024077
Epigenetic modifications play an important role in cellular senescence, and enhancer of zeste homolog 2 (EZH2) is a key methyltransferase involved in epigenetic remodeling in multiple myeloma (MM) cells. We have previously demonstrated that GSK126, a specific EZH2 inhibitor, exhibits anti-MM therapeutic efficacy and safety in vivo and in vitro; however, its specific mechanism remains unclear. This study shows that GSK126 induces cellular senescence in MM, which is characterized by the accumulation of senescence-associated heterochromatin foci (SAHF) and p21, and increased senescence-associated β galactosidase activity. Furthermore, EZH2 is inhibited in ribonucleotide reductase regulatory subunit M2 (RRM2)-overexpressing OCI-MY5 and RPMI-8226 cells. RRM2 overexpression inhibits the methyltransferase function of EZH2 and promotes its degradation through the ubiquitin-proteasome pathway, thereby inducing cellular senescence. In this senescence model, Lamin B1, a key component of the nuclear envelope and a marker of senescence, does not decrease but instead undergoes aberrant accumulation. Meanwhile, phosphorylation of extracellular signal-regulated protein kinase (ERK1/2) is significantly increased. The inhibition of ERK1/2 phosphorylation in turn partially restores Lamin B1 level and alleviates senescence. These findings suggest that EZH2 inhibition increases Lamin B1 level and induces senescence by promoting ERK1/2 phosphorylation. These data indicate that EZH2 plays an important role in MM cellular senescence and provide insights into the relationships among Lamin B1, p-ERK1/2, and cellular senescence.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025156
CD19-directed chimeric antigen receptor T (CAR-T) cell therapy is promising for treating relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), yet its long-term efficacy remains limited by CAR-T-cell exhaustion. Given the broad immunomodulatory activities of vitamin D, we investigate whether its active form, 1α,25(OH)2D3, enhances CAR-T-cell functionality and improves therapeutic outcomes. We demonstrate that 1α,25(OH)2D3 treatment significantly mitigates exhaustion and enhances the antitumor activity of CD19 CAR-T cells derived from both healthy donors and DLBCL patients, which is further validated in xenograft mouse models. Mechanistically, we show that 1α,25(OH)2D3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH)2D3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261508
This study optimized the processing parameters for two distinct preparations of Sophora japonica (SJ) — stir-fried SJ and charred SJ — using a multi-component quantification and color-correlation framework. Nine marker compounds (5-hydroxymethylfurfural, protocatechuic acid, rutin, isoquercitrin, quercetin, kaempferol-3-O-rutinoside, narcissin, kaempferol, and isorhamnetin) plus alcohol-soluble extract content were quantified by UPLC. A Box-Behnken design-response surface methodology (BBD-RSM) evaluated roasting power, roasting time, and feedstock quantity. CRITIC weighting assigned objective coefficients to the ten indicators. An IRIS electronic eye captured color values (L*, a*, b*), and correlations with chemical markers were analyzed using SPSS 20.0 and Origin 2024. The optimal stir-fried SJ conditions were 900 W, 5.5 min, and 115 g, yielding a composite score of 67.33 (RSD 2.29%). For charred SJ, 1,600 W, 3 min, and 100 g produced a score of 78.98 (RSD 0.70%). Validation across three batches confirmed process stability. Color-component correlation revealed that L* and b* were significantly positively correlated with rutin, kaempferol-3-O-rutinoside, and narcissin, and negatively correlated with kaempferol, quercetin, and isorhamnetin. The a* value was positively correlated with protocatechuic acid, isoquercitrin, quercetin, kaempferol, and isorhamnetin. These findings establish a quantitative color-based control strategy for SJ processing, linking visual appearance to hemostatic pharmacodynamics and offering a practical tool for quality assessment and clinical application.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21252
BACKGROUND: The occurrence of major depressive disorder is typically associated with genetic and environmental factors. Currently, the diagnosis of major depressive disorder mainly relies on clinical interviews and symptom assessments, lacking clear and reproducible biological markers. This can lead to misdiagnosis and missed diagnoses, delaying the timing of treatment. OBJECTIVE: To identify druggable genes that may act as potential therapeutic targets for major depressive disorder by conducting comprehensive genome-wide Mendelian randomization analysis. METHODS: By integrating expression quantitative trait locus (eQTL) data and protein quantitative trait locus (pQTL) data from pharmacologically actionable genes with genome-wide association study (GWAS) data on major depressive disorder (including 177 377 cases and 445 321 controls), Mendelian randomization analysis was conducted to identify druggable genes that have a causal relationship with major depressive disorder. Additionally, enrichment analysis, protein-protein interaction network construction, drug target identification, and molecular docking simulations were performed to further explore potential therapeutic strategies. RESULTS AND CONCLUSION: A total of 4 394 druggable genes were analyzed, and 21 druggable genes considerably associated with major depressive disorder were identified. Bayesian colocalization analysis indicated that BTN3A3, CISD1, and PSMB4 had posterior probabilities of hypothesis 4 (H4.abf) > 0.5, supporting the possibility of shared causal variants. GO enrichment analysis mainly involved 'antigen processing and presentation', 'protein degradation and processing', 'mitochondrial outer membrane', and 'immune receptor activity' pathways related to major depression. Protein-protein interaction network analysis showed moderate connectivity among the identified genes (21 nodes, 14 edges). Drug target identification determined gemcitabine (CID 60750), fucose (CID 17106), and isococculidine (CID 2826) as main candidate compounds, which had strong associations with several key genes. Molecular docking analysis revealed stable drug-protein interactions, with isococculidine showing the most stable binding energy (-52.74 kJ/mol) with BTN3A3. In conclusion, Mendelian randomization combined with genomics and structural biology analysis provides valuable decision-making basis for target prioritization and drug repurposing, offering new ideas and directions for efficient utilization of basic research resources and drug development for major depressive disorder.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21283
BACKGROUND: High cumulative remnant cholesterol levels are associated with the risk of various metabolic diseases, but their impact on bone quality remains to be explored. OBJECTIVE: To investigate the effects of high cumulative remnant cholesterol levels on bone mass, microstructure, and biomechanical properties in high-fat diet treated mice. METHODS: Ten healthy male SPF-grade C57BL6 mice were randomly allocated into normal control group and high-fat diet group. The normal control group was fed a normal diet for 20 weeks, while the high-fat diet group was fed a high-fat, high-cholesterol diet for 20 weeks. Mouse body mass was detected every week. After 20 weeks of feeding, serum levels of total cholesterol, remnant cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, type I collagen carboxy-terminal cross-linked telopeptide, and type I procollagen amino-terminal propeptide were measured. Micro-CT was used to assess the microstructure of femoral cancellous and cortical bone. Three-point bending test was performed to measure the elastic modulus and maximum stress of the femur. RT-qPCR was used to detect the mRNA expression of RUNT-related transcription factor 2, type I collagen, osteocalcin, alkaline phosphatase, osteoprotegerin, receptor activator of nuclear factor-κB ligand, nuclear factor of activated T cells 1, and cathepsin K in the tibia. Pearson correlation analysis was used to analyze the correlation between remnant cholesterol, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels and bone mineral density, as well as the correlation between remnant cholesterol levels and bone volume fraction, trabecular number, structure model index, and trabecular separation. RESULTS AND CONCLUSION: (1) From the 6th week of feeding, the body mass of mice in the high-fat diet group was higher than that in the control group (P < 0.05). The serum levels of total cholesterol, remnant cholesterol, and type I collagen carboxy-terminal cross-linked telopeptide in the high-fat diet group were higher than those in the control group (P < 0.05). (2) Micro-CT detection showed that compared with the control group, the bone microstructure of mice in the high-fat diet group underwent obvious degeneration, specifically manifested as significantly decreased bone mineral density, bone volume fraction, trabecular connectivity density, and trabecular number in cancellous bone, and significantly increased trabecular separation, structure model index, and trabecular pattern factor (P < 0.05). There were no significant changes in cortical bone thickness, volume, and area (P > 0.05). There was no significant difference in elastic modulus and maximum stress of the femur between the two groups (P > 0.05). (3) RT-qPCR detection showed that the mRNA expression of RUNT-related transcription factor 2, type I collagen, osteocalcin, alkaline phosphatase, and osteoprotegerin in the high-fat diet group was lower than that in the control group (P < 0.05), while the mRNA expression of nuclear factor of activated T cells 1 and cathepsin K was higher than that in the control group (P < 0.05). (4) Pearson analysis showed that remnant cholesterol and total cholesterol levels were significantly negatively correlated with bone mineral density (P < 0.05), and remnant cholesterol was significantly negatively correlated with bone volume fraction and trabecular number (P < 0.05), and significantly positively correlated with structure model index and trabecular separation (P < 0.05). These results indicate that remnant cholesterol may reduce bone quality by affecting the balance of bone turnover.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21367
BACKGROUND: Extracorporeal shock wave therapy, as a non-invasive and non-invasive treatment technique, is widely used in various fields. Currently, there is no systematic analysis of the latest research status, hot topics, and development trends in this field. OBJECTIVE: To analyze the research status, hotspots, and trends of extracorporeal shock wave therapy using bibliometric visualization software over the past 10 years. METHODS: Relevant literature in the field of extracorporeal shock wave therapy was retrieved from the Web of Science core database from January 1, 2015 to December 31, 2024. CiteSpace was used for analyzing publication volume, collaborations among countries/regions, institutions, and authors, citation analysis of journals and co-cited literature. Additionally, keyword co-occurrence, clustering, and burst analyses were conducted, and visualized knowledge maps were generated. RESULTS AND CONCLUSION: A total of 1 641 articles were included. The number of publications in the field of extracorporeal shock wave therapy is generally on the rise over the past 10 years. China, the United States, and Italy are the top three countries in terms of publication volume, while Chang Gung University, the University of California, and Harvard University are the top three research institutions. A total of 280 journals published articles related to extracorporeal shock wave therapy, among which Clinical Orthopaedics and Related Research was the most cited journal, and PLoS One had the highest centrality. The author with the highest publication volume was Wang, Ching-Jen from Chang Gung University, and there was little collaboration among high-yield authors and their research groups. The hot keywords in this field were mainly double-blind, pain, erectile dysfunction, plantar fasciitis, lateral epicondylitis, etc. Burst keywords included rabbit, ischemia, myocardial infarction, fasciopathy, muscle spasm, and erectile function, showing diversified research directions. Extracorporeal shock wave therapy is a non-invasive and safe treatment method. Pain management, musculoskeletal system diseases, and urological-related diseases are the research hotspots in the field of extracorporeal shock wave therapy in the past 10 years, and research on related mechanisms is also a focus of interest. Future research directions may focus on standard parameter research and long-term efficacy verification of extracorporeal shock wave therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21459
BACKGROUND: Odanacatib effectively exerts anti-inflammatory effects and promotes alveolar bone repair in periodontitis-affected areas. However, multiple injections are required to ensure efficacy, which is cumbersome. OBJECTIVE: To prepare an odanacatib-loaded microsphere-gel composite sustained-release carrier and characterize its biocompatibility. METHODS: (1) Poly(lactic-co-glycolic acid) microspheres loaded with different masses of odanacatib (denoted as ODN-MS) were prepared by emulsion-solvent evaporation method. Based on drug loading and encapsulation efficiency, microspheres prepared with 5 mg odanacatib and 40 mg PLGA were selected for subsequent experiments. Different masses of ODN-MS were mixed with methacrylated gelatin (GelMA) solution to prepare gel composite sustained-release carriers (denoted as ODN-MS-Gel), with ODN-MS mass concentrations of 250 and 500 μg/mL. The microstructure and in vitro drug release properties of ODN-MS and 250 μg/mL ODN-MS-Gel were characterized. (2) Rabbit bone marrow mesenchymal stem cells (BMSCs) were cultured with extracts of GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 and 500 μg/mL ODN-MS-Gel. CCK-8 assay was used to detect cell proliferation. Rabbit BMSCs were cultured with extracts of GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 μg/mL ODN-MS-Gel. Live/dead staining was used to detect cell viability. Rabbit BMSCs were seeded on GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 μg/mL ODN-MS-Gel. Phalloidin staining and scanning electron microscopy were used to observe cell adhesion. RESULTS AND CONCLUSION: (1) Under optical microscope, ODN-MS were spherical, uniformly distributed, and without agglomeration. Scanning electron microscopy showed that ODN-MS surface had fine porous structure; 250 μg/mL ODN-MS-Gel hydrogel had porous structure, and ODN-MS were distributed in the porous structure. Both ODN-MS and 250 μg/mL ODN-MS-Gel could achieve sustained drug release, and the 250 μg/mL ODN-MS-Gel system released drug more gently, achieving dual sustained-release effect. (2) CCK-8 assay showed that 250 and 500 μg/mL ODN-MS-Gel extracts could promote the proliferation of rabbit BMSCs. Live/dead staining showed that 250 μg/mL ODN-MS-Gel extract did not affect the viability of rabbit BMSCs. Phalloidin staining and scanning electron microscopy showed that compared with the other two materials, 250 μg/mL ODN-MS-Gel promoted the adhesion of rabbit BMSCs. These results indicate that ODN-MS-Gel can achieve sustained release of odanacatib and has good biocompatibility.