Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03718-z
Background Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation is a key driver of chronic kidney disease (CKD), with immune dysregulation, particularly among lymphocytes, contributing to early disease pathology. To explore the role of apolipoprotein A4 (Apoa4) in regulating immune cell metabolism and function, we establish high-fat diet-induced obese (DIO) models using wild-type and Apoa4-knockout (KO) mice. KO mice exhibit exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing reveals that Apoa4 deletion remodeled the renal immune-metabolic landscape. This remodeling broadly compromises the immune functions of T, NK, and B cells, even as it expands the proportions of cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravates metabolic dysregulation and oxidative stress and downregulates the expression levels of key effector genes, including Ifng and Il1b. Furthermore, the regulatory network activities of key transcription factors, such as Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells, are perturbed. CellChat analysis predicts disruptions in pro-inflammatory (IFN-II and IL-1), immunoregulatory (FASLG), and metabolic regulatory (ENHO and ANGPTL) signaling, alongside enhanced IL-2-mediated suppression. These findings are corroborated by flow cytometry, immunofluorescence staining, and qPCR. Our results establish Apoa4 as a crucial regulator of lymphocyte metabolic and immune homeostasis in the early stages of obesity-associated CKD.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024173
Pyroptosis, a newly discovered form of programmed cell death, is involved in the occurrence, development and drug resistance of a variety of tumors and has attracted increasing attention in recent years. LINC00365 is a novel lncRNA that has rarely been reported before. We previously reported that LINC00365 expression in colorectal cancer is closely associated with poor patient outcomes. Additionally, LINC00365 was confirmed to be positively correlated with miR-221-5p, and miR-221-5p is negatively correlated with gasdermin-D (GSDMD) in colorectal cancer tissues. Bioinformatics analysis and luciferase reporter gene experiments revealed that GSDMD is the target gene of miR-221-5p. Cell function experiments and nude mouse tumor transplantation assays confirmed that LINC00365 could regulate the expressions of pyroptosis-related proteins such as Caspase-1, Caspase-11, NLRP3 and GSDMD. RNA pulldown and RNA immunoprecipitation experiments further elucidated the mechanism by which LINC00365 regulates miR-221-5p. In the present study, we observe that LINC00365 promotes the expression of miR-221-5p by binding to the Dicer enzyme to inhibit GSDMD and plays an antipyroptotic role. Our findings suggest that LINC00365 may serve as a molecular biomarker for estimating the prognosis of patients with colorectal cancer and as a potential therapeutic target for colorectal cancer.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21225
BACKGROUND: The crescent sign is a significant radiological feature in the progression of steroid-induced osteonecrosis of the femoral head (SIONFH), indicating the separation and defect of articular cartilage and subchondral bone. The appearance of the crescent sign is associated with the mid-to-late stages of the disease and poor prognosis. However, studies on the specific pathological characteristics and progression patterns of articular cartilage in SIONFH remain unclear. OBJECTIVE: To observe the pathological features of articular cartilage in specimens from different stages of SIONFH, explore the progression and pathological mechanisms, and elucidate the formation mechanism of the crescent sign, providing a theoretical basis for optimizing hip-preserving strategies. METHODS: Femoral head specimens were collected from patients with SIONFH who underwent total hip arthroplasty at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2021 to 2024. According to the ARCO staging, they were divided into mild, moderate, and severe collapse groups, with fresh femoral neck fracture specimens as controls. All specimens were cut coronally, and the folded cartilage surface in the necrotic area was taken; control group took corresponding area. Hematoxylin-eosin staining and Safranin O-fast green staining were used for morphological observation, immunohistochemistry and western blot for biomarker expression, and apoptosis kit for apoptosis level. RESULTS AND CONCLUSION: (1) Gross observation: The control group showed smooth cartilage surface without folds or hyperplasia, no separation or defect between articular cartilage and subchondral bone, and tough texture. In SIONFH specimens, obvious folds were visible on the cartilage surface, with separation and defects between articular cartilage and subchondral bone, and a loose sensation on pressing. (2) Pathological observation: In the control group, chondrocytes in each layer were arranged neatly, cartilage matrix stained uniformly, tidemark was intact and continuous, calcified cartilage layer and subchondral bone connection was clear and complete, and bone trabeculae were arranged neatly. In SIONFH specimens, chondrocytes were disorganized, empty lacunae increased, matrix staining loss of varying degrees, tidemark duplication and loss, calcified cartilage layer showed numerous cavities and sclerosis, with granulation tissue invasion into cavities, separation and defects between calcified cartilage and subchondral bone, and abundant proliferative granulation tissue in subchondral bone trabecular spaces. (3) Immunohistochemistry: In SIONFH specimens, positive staining of Runt-related transcription factor 2, matrix metalloproteinase 13, matrix metalloproteinase 3, and collagen type I alpha 2 chain increased in calcified cartilage layer and deep cartilage; vascular endothelial growth factor A, hypoxia-inducible factor 1 alpha, interleukin-1 beta, and tumor necrosis factor alpha positive staining increased in subchondral bone trabecular spaces and deep cartilage granulation and scar tissue. (4) Western blot results showed decreased expression of collagen type II alpha 1 chain and SOX9, and increased expression of Runt-related transcription factor 2, matrix metalloproteinase 13, hypoxia-inducible factor 1 alpha, and vascular endothelial growth factor A in SIONFH specimens. (5) Caspase3/7 activity in SIONFH samples was significantly higher than that in the control group, positively correlated with the degree of collapse. (6) These results indicate that articular cartilage lesions in SIONFH mainly concentrate in the deep cartilage and calcified cartilage around the necrotic area. Necrosis of subchondral bone leads to changes in local microenvironment and elastic modulus, causing sclerosis of calcified cartilage. With continued weight-bearing, stress concentration at the necrosis-sclerosis junction leads to brittle fracture, which is the starting point of fracture. Bone and cartilage fracture leads to destruction of the subchondral cortical bone barrier, and invasion of granulation tissue from subchondral bone trabecular spaces directly stimulates calcified cartilage and deep cartilage, resulting in terminal differentiation, apoptosis, matrix degradation, and cavity formation of chondrocytes, leading to decreased repair capacity of articular cartilage. The diseased cartilage cannot properly interlock with subchondral bone, and with disease progression, extensive separation and defects eventually appear between bone and cartilage, manifesting as the crescent sign on imaging.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21269
BACKGROUND: Current research in rheumatoid arthritis focuses on iron metabolism-related proteins and the effects of ferroptosis on immune cells. This study proposes new approaches to target ferroptosis in the treatment of rheumatoid arthritis from the perspective of traditional Chinese medicine. These approaches include developing new traditional Chinese medicine therapies, creating individualized treatment plans based on patients’ genes and biomarkers, optimizing therapeutic strategies, and improving symptoms. These strategies aim to facilitate early treatment and improve prognosis. OBJECTIVE: Bioinformatics was applied to investigate the molecular mechanism of treating rheumatoid arthritis from the perspective of ferroptosis, and to screen potential traditional Chinese medicines and active ingredients, opening up a new way for the treatment of rheumatoid arthritis. METHODS: The Gene Expression Omnibus database, maintained by the National Center for Biotechnology Information, is primarily used to store and share high-throughput gene expression, microarray, and sequencing data. The Gene Expression Omnibus database enables researchers to search and analyze genomic data related to various diseases. This study is based on publicly available summary statistics databases and does not require ethical approval. The Gene Expression Omnibus database was searched for datasets related to rheumatoid arthritis that met the screening criteria. The Sanger sequencing platform was then used to obtain the transcriptome data of rheumatoid arthritis. Finally, the limma algorithm was applied to screen the differentially expressed genes. Meanwhile, the ferroptosis-related gene set was extracted from the FerrDb database. Through integration analysis, we obtained the intersection of the differentially expressed genes and the ferroptosis-related genes. We constructed a protein interaction network and performed network topology analysis. Then, using DAVID Bioinformatics Resources 6.8, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to explore biological functions and signaling pathways. Finally, the SymMap platform was used to identify natural medicines, and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to find small molecule compounds and corresponding targets for molecular docking analysis. RESULTS AND CONCLUSION: Two datasets, GSE55457 and GSE55235, were identified from the GEO database, and 340 common differentially expressed targets were obtained via limma analysis. A total of 487 ferroptosis-related targets were collected from the FerrDb platform, and 17 common targets related to ferroptosis and rheumatoid arthritis were obtained after intersection. A protein interaction network was constructed using the 17 common targets, containing 16 target proteins and 33 interactions. Core targets such as EGFR, AR, MAPK8, CDKN1A, JUN, ATM, and EGR1 occupied important positions in the network. Five core targets (EGFR, AR, MAPK8, CDKN1A, and JUN) were identified as key ferroptosis-related targets in rheumatoid arthritis. GO and KEGG enrichment analyses showed that treating rheumatoid arthritis via the ferroptosis pathway may be related to DNA binding processes and SMAD2/3 signaling pathways. Molecular docking results showed that natural small molecule compounds such as progesterone, estradiol, and quercetin could form good binding with core targets, providing new directions for drug development and research in rheumatoid arthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21366
BACKGROUND: In recent years, the research on stroke rehabilitation robots has developed rapidly both domestically and internationally. It involves the intersection of multiple disciplines such as rehabilitation medicine, artificial intelligence, virtual reality, and sensor technology, and has become a research hotspot in the field of stroke rehabilitation. OBJECTIVE: To grasp the current status and hotspots of research in this field through a comparative analysis of domestic and international studies, and to predict future development trends. METHODS: The Web of Science Core Collection and CNKI databases were selected as data sources to collect relevant literature on stroke rehabilitation robots from 2005 to 2025. CiteSpace 6.2.R3 visualization software and bibliometric methods were used to compare the annual publication volume, countries, and keywords of included studies, analyze differences between domestic and international research, and summarize and prospect frontier technologies. RESULTS AND CONCLUSION: A total of 3,522 English and 717 Chinese articles were included. From 2005 to 2025, 81 countries participated in research, forming a cross-continental cooperation network centered on the United States, China, and Italy. Publication trends showed a yearly increase both domestically and internationally, with an average annual growth rate of 13.06% internationally and 20.17% domestically, the latter being about 1.5 times faster. Research trends indicated that international research has gone through stages of mechanism exploration, clinical translation, and intelligent integration, currently focusing on multidisciplinary intersection and technology integration such as robot perception systems and machine learning. Domestic research started with technology introduction and clinical validation, gradually developing into intelligent integration and precise rehabilitation, with significant progress in multimodal fusion such as brain-computer interfaces and virtual reality in recent years. Research hotspots: international research mainly focuses on design optimization of robot technology and multimodal technology integration, while domestic research emphasizes the impact on functional outcomes after stroke. Additionally, international research is more advanced in neurophysiological signal fusion, advanced algorithms, and model construction, whereas domestic research shows unique advantages in combining rehabilitation technology with traditional Chinese medicine therapies. The results indicate that the field of stroke rehabilitation robots is in a rapid development stage, with technology integration and clinical translation being the core trends for future development. Although domestic and international research have different emphases, both are committed to improving the intelligence, lightweight design, and clinical practicality of rehabilitation robots. Domestic research started later but is developing rapidly, gradually building a multimodal technology system characterized by intelligent integration and precise rehabilitation. In the future, domestic and international research can complement each other, with China contributing clinical big data and application scenarios, and foreign countries providing core technologies and innovative methods, jointly advancing breakthroughs and applications in stroke rehabilitation robot technology.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21390
BACKGROUND: Lunge exercises are often used in strengthening programs for patellofemoral pain syndrome and have been shown to help strengthen the quadriceps. However, limited data exist to evaluate the effects of lunge exercises with medial or lateral resistance on patellofemoral joint stress and lower limb muscle activation. OBJECTIVE: To compare the effect of three lunge exercises (traditional lunge, lunge with hip adduction resistance, and lunge with hip abduction resistance) on lower limb muscle activation and patellofemoral joint stress in subjects with patellofemoral pain syndrome and health control group. METHODS: Totally 29 subjects with patellofemoral pain syndrome and 29 healthy subjects completed three different lunge exercises. Lower limb dynamics and electromyography data were simultaneously acquired using an infrared motion capture system, a three-dimensional force table, and a surface electromyography analyzer. A mixed-design analysis of variance was used to determine the effects of group and exercise on patellofemoral joint stress and lower limb muscle activation characteristics during different lunge exercises. RESULTS AND CONCLUSION: (1) During the squatting phase, the vastus lateralis muscle activation was significantly lower in both groups during the lunge exercises with hip adduction (P < 0.05), while the vastus medialis/vastus lateralis activation ratio was significantly increased in the healthy group (P < 0.05). In the patellofemoral pain syndrome group, the gluteus medius activation was significantly increased (P < 0.05) and the peak patellofemoral joint stress was significantly reduced (P < 0.05) during the lunge with hip abduction. (2) During the pushing phase, the vastus lateralis activation was significantly lower in both groups during the lunge with hip abduction (P < 0.05), and the patellofemoral pain syndrome group showed significantly reduced peak patellofemoral joint stress (P < 0.05) and enhanced gluteus medius activation (P < 0.05). In the healthy group, the vastus medialis/vastus lateralis activation ratio was significantly increased during the lunge with hip adduction (P < 0.05), and the patellofemoral pain syndrome group had significantly lower peak patellofemoral joint stress than the healthy group (P < 0.05). (3) These findings suggest that traditional lunge can be one of the preferred training methods for strengthening the quadriceps in the early rehabilitation of patellofemoral pain syndrome. Lunge exercises with lateral adduction/abduction resistance have advantages in improving vastus medialis/vastus lateralis activation imbalance, strengthening gluteus medius activation, and reducing patellofemoral joint stress during squatting, which may help rebuild neuromuscular control of the lower limb kinetic chain in the later rehabilitation stage. For patients with patellofemoral pain syndrome, lunge with lateral abduction resistance is more recommended to alleviate pain and improve function.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.06.013
AIM: To investigate the role of Enterococcus faecalis (E. faecalis) in colorectal cancer (CRC) chemoresistance and elucidate the underlying molecular mechanisms. METHODS: Conditioned media (CM) were collected from cultures of E. faecalis treated with oxaliplatin or 5-fluorouracil (5-FU). The effects of these media on CRC chemoresistance were evaluated using in vitro functional assays and in vivo xenograft models in nude mice. Bioinformatics analysis was conducted to identify candidate genes associated with E. faecalis-induced chemoresistance. Gain- and loss-of-function experiments were performed to assess the role of MOB3B in regulating CRC cell proliferation and drug sensitivity. RT-qPCR, Western blot, and immunohistochemistry were used to validate the molecular mechanisms involved. Metabolomic profiling identified key metabolites in E. faecalis-oxaliplatin CM, and their roles in drug resistance were also confirmed. RESULTS: Compared with oxaliplatin treatment alone, E. faecalis-oxaliplatin CM significantly promoted CRC cell growth and chemoresistance in vitro (P<0.01). Tumors treated with E. faecalis-oxaliplatin CM exhibited significantly larger volumes and faster growth in vivo (P<0.01). Mechanistically, down-regulation of MOB3B mediated the chemoresistance-promoting effects of E. faecalis-oxaliplatin CM (P<0.01). Overexpression of MOB3B inhibited CRC cell proliferation and enhanced chemosensitivity, whereas MOB3B knockdown produced the opposite effect (P<0.01). Metabolomic analysis revealed elevated lactate levels in the E. faecalis-oxaliplatin CM (P<0.01). Lactate inhibition significantly reduced CRC cell proliferation, reversed chemoresistance, and restored MOB3B expression (P<0.01). CONCLUSION: E. faecalis promotes chemoresistance in CRC through lactate-mediated down-regulation of MOB3B, highlighting MOB3B as a potential therapeutic target for overcoming CRC chemoresistance.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.06.009
AIM: To investigate the contribution of Enterococcus faecalis (E. faecalis) to chemoresistance in colorectal cancer (CRC) and uncover the underlying mechanisms. METHODS: Bioinformatics analyses were performed to evaluate the expression of MOB3B, an Mps-one binder coactivator (MOB) protein family member, and its clinical implications in CRC patients. E. faecalis was co-cultured with CRC cells to assess its effect on MOB3B expression. MOB3B was overexpressed or silenced in CRC cells to determine its effects on cell viability and chemosensitivity. The LRRC19-dependent mechanism was investigated through additional bioinformatics analyses. Immunohistochemical staining of clinical CRC tissues was performed to correlate MOB3B expression with Tumour Regression Grade. RESULTS: MOB3B down-regulation was associated with adverse clinicopathological characteristics and poor prognosis in CRC patients. Co-culture with E. faecalis down-regulated MOB3B expression in CRC cells. MOB3B overexpression decreased cell viability, while its silencing increased viability. MOB3B overexpression also reversed chemoresistance in CRC cells. Bioinformatics analyses revealed that MOB3B modulated resistance to oxaliplatin and 5-fluorouracil in an LRRC19-dependent manner. Low MOB3B expression correlated with high Tumour Regression Grade in clinical tissues. CONCLUSION: These findings indicate that Enterococcus faecalis promotes chemotherapy resistance by down-regulating MOB3B in colorectal cancer, and that MOB3B may serve as a potential marker for evaluating chemosensitivity and prognosis in CRC patients. The role of E. faecalis abundance as a clinical biomarker requires further validation in prospective cohorts.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025171
Obesity-induced metabolic inflammation drives chronic kidney disease (CKD), with lymphocyte dysregulation contributing to early pathology. We established high-fat diet-induced obese (DIO) models in wild-type and Apoa4-knockout (KO) mice to investigate apolipoprotein A4 (Apoa4) in immune-metabolic regulation. KO mice exhibited exacerbated insulin resistance and renal lipid accumulation. Single-cell RNA sequencing (scRNA-seq) of renal immune cells revealed that Apoa4 deletion remodeled the immune-metabolic landscape, compromising T, NK, and B cell functions while expanding cytotoxic Gzma+ NK cells and Derl3+ plasma cells. Mechanistically, Apoa4 deletion aggravated metabolic dysregulation and oxidative stress, downregulating effector genes including Ifng and Il1b. Transcription factor regulatory networks were perturbed: Lef1 and Runx3 in Cd8+ T cells; Irf8, T-bet, and Eomes in NK cells; and Tcf4, Lmo2, and Xbp1 in B cells. CellChat predicted disrupted pro-inflammatory (IFN-II, IL-1), immunoregulatory (FASLG), and metabolic (ENHO, ANGPTL) signaling, with enhanced IL-2-mediated suppression. Flow cytometry, immunofluorescence, and qPCR validated these findings. Sequencing depth averaged 278,276 reads/cell (WT) and 197,768 reads/cell (KO), ensuring robust detection of low-abundance transcripts despite modest cell capture. Apoa4 is a critical regulator of lymphocyte metabolic and immune homeostasis in early obesity-associated CKD.