Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03660-0
Background Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. Methods 10× Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. Results We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. Conclusion Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025107
The cGAS-STING pathway is a critical regulator of innate immunity. When cyclic GMP-AMP synthase (cGAS) detects aberrant cytosolic DNA, it synthesizes the second messenger 2′3′-cGAMP, which binds and activates stimulator of interferon genes (STING) on the endoplasmic reticulum (ER). Activated STING then translocates to the Golgi apparatus, where it recruits and mutually phosphorylates TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). Phosphorylated IRF3 dimerizes and translocates to the nucleus, where it drives the production of type 1 interferons (IFN-1). In addition to being activated by IFN-1, STING also engages the nuclear factor kappa-B (NF-κB) pathway to induce the production of proinflammatory cytokines and chemokines. Moreover, IFN-1 signaling upregulates the expressions of interferon-stimulated genes (ISGs) through the IFN-α receptor (IFNAR). STING-associated vasculopathy with onset in infancy (SAVI) is a severe pediatric autoimmune disease caused by heterozygous gain-of-function mutations in STING, such as the N154S variant in humans and N153S in mice. Initially, classified as an interferonopathy due to constitutive activation of the STING pathway, SAVI is characterized by systemic inflammation, vasculopathy, interstitial lung disease, T-cell cytopenia, skin ulcerations, and premature death. However, recent studies challenge this paradigm, demonstrating that SAVI pathology develops independently of IFNAR-1 and IRFs (IRF3 and IRF7) [1,2], suggesting that alternative mechanisms drive disease progression. Emerging evidence indicates that STING restricts microbial infection through noncanonical autophagy and cell death pathways [3,4]. These functions may depend on its recently identified role as a proton channel in the Golgi apparatus [4,5]. Xun et al. [4] demonstrated that ligand-bound STING forms an ion channel in its transmembrane domain, facilitating proton efflux from post-Golgi vesicles and inducing Golgi deacidification. This raises a critical question: could STING-mediated Golgi deacidification be a potential mechanism underlying SAVI pathogenesis? A recent study by Poddar et al. [6] identified ADP ribosylation factor GTPase-activating protein 2 (ArfGAP2), which is involved in coatomer protein-1 (COP-1) coating in Golgi vesicles, as a key regulator of both STING signaling and proton channel activity, offering novel therapeutic insights for SAVI. First, to elucidate the role of STING in SAVI pathogenesis, they conducted a genome-wide CRISPR-Cas9 screen in T cells resistant to chronic STING activation and identified ArfGAP2 as a critical STING modulator among multiple Golgi-related proteins. Further investigation revealed that genetic ablation of ArfGAP2 in Jurkat T cells significantly attenuated STING-mediated ISG induction. Compelling evidence indicates that STING activation is associated with its subcellular location [7]. While ArfGAP family proteins typically regulate Golgi membrane trafficking, vesicle transport, and cargo sorting [8], Poddar et al. [6] surprisingly reported that ArfGAP2 enhances STING-mediated ISG induction and promotes LC3 lipidation without altering STING palmitoylation or its Golgi localization. Further experiments revealed that ArfGAP2 enhances STING signaling and IFN-β secretion in mouse bone marrow-derived macrophages (BMDMs). In addition to promoting IFN-1 induction, ArfGAP2 promotes the secretion of NF-κB-dependent proinflammatory cytokines activated by STING in THP-1 monocytes [6]. In addition to inducing ISGs and NF-κB signaling, activated STING acts as a proton channel triggering Golgi deacidification [4]. Given the well-established importance of the Golgi pH in regulating enzyme activity, protein modification, and membrane trafficking [9], researchers have further explored how STING and ArfGAP2 modulate cargo transport and secretion. They reported that the loss of ArfGAP2 impairs STING-mediated proton channel activity in the Golgi, leading to a lower luminal pH. Moreover, ArfGAP2-deficient cells presented significant alterations in the cell surface proteome upon STING activation, accompanied by altered sorting, secretion and trafficking rates of specific protein cargos in the Golgi [6].
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025230
The diverse antibodies of adaptive immunity comprise an antibody repertoire that combats various pathogens. This repertoire is shaped by both intrinsic antibody gene diversification and extrinsic cellular selection. Conversely, an antibody repertoire contains multiple layers of immunological information, including the history of pathogen exposure. High-throughput sequencing-based antibody repertoire cloning approaches have revealed unexpected features of adaptive immunity. However, our understanding of antibody repertoire data is still in its infancy. In this review, we introduce the emerging concepts and discuss the application of deep learning approaches to understanding antibody repertoires. First, we introduce the definition and functional features of antibody clonotype. Next, we review the evolution of antibody clonotypes and discuss potential antibody repertoire-directed vaccination approaches. Lastly, we summarize the application of deep learning in predicting antibody binding, generating specific antibodies, and making immunologic diagnoses. Recently, artificial intelligence (AI) has made revolutionary progress in biology. Leveraging high-dimensional antibody repertoire information, deep learning models have the potential to transform our understanding of antibody repertoire.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025114
Bladder cancer (BCa) is one of the most common malignant tumors of the urinary system, but its pathogenesis is still unclear. T1G3 BCa is particularly invasive and relapses readily after treatment, with progression to invasive cancer or distant metastasis. Therefore, identification of the molecular mechanism by which it invades and metastasizes to guide treatment and predict patient prognosis is needed. Cofilin1 plays an important role in regulating gene expression and the invasiveness of tumors. In this study, we show that Cofilin1 is highly expressed in BCa and lymph nodes with metastasis, which is positively related to the grade of BCa, and is significantly related to clinicopathological parameters and cancer-specific survival. Phenotypic analysis reveals that Cofilin1 knockout inhibits the proliferation and migration of BCa cells, whereas Cofilin1 overexpression promotes the opposite phenotype. Cofilin1 binds to cortactin, thereby reducing the expression of F-actin and promoting the formation of invadopodia in BCa cells. Further experiments reveal that TCF7L2 can bind to the promoter of Cofilin1 and transactivate it, promoting a malignant phenotype. TCF7L2 may also reverse the inhibitory effect of miR-206 on the binding of Cofilin1 and cortactin and promote the metastasis of BCa by inhibiting the transcription maturation of miR-206. This study confirms that Cofilin1 is an oncogene in T1G3 BCa, and the TCF7L2/miR-206/Cofilin1 signaling pathway plays an important role in the formation of invadopodia in BCa.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024078
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like (Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p (Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025139
Sepsis-associated acute liver injury (SALI) is a frequent and clinically severe complication of sepsis, in which inflammatory responses and oxidative stress are involved. Angelicin (ANG), one of the main active components in the traditional Chinese medicine Psoralea corylifolia Linn., has anti-inflammatory and antioxidant bioactivities. In this study, the protective effect of ANG on SALI and its specific mechanism are investigated by establishing a mouse model of caecal ligation and puncture (CLP)-induced SALI and an in vitro sepsis model in LPS-stimulated AML12 cells. These results show that ANG can alleviate liver injury and improve liver function in SALI mice. ANG decreases the mRNA expression levels of the pro-inflammatory factors Il-1β, Il-6, and Tnf-α and increases the mRNA expression level of the anti-inflammatory factor Il-10, which suggests its anti-inflammatory effects. The results of the biochemical kit assay and DHE staining show that ANG can decrease the levels of MDA and ROS and increase the level of GSH and the activities of CAT and SOD, which suggests that ANG has antioxidant effects. Mechanistically, ANG exerts anti-inflammatory effects by inhibiting the NF-κB and p38 MAPK pathways and exerting antioxidant effects by activating the Nrf2/Keap1 pathway. Additionally, cell transfection experiments indicate that activation of the Nrf2/Keap1 pathway by ANG may depend on the inhibition of the NF-κB pathway. In conclusion, ANG attenuates SALI by inhibiting the NF-κB and p38 MAPK pathways, thereby activating the Nrf2/Keap1 pathway and making it a promising therapeutic intervention for SALI.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025149
Lung squamous cell carcinoma (LUSC) is a common subtype of non-small cell lung cancer, with limited treatment options and poor patient prognosis. Currently, common driver mutations in lung adenocarcinoma rarely occur in LUSC; the mutated genes found in LUSCs lack corresponding targeted drugs. Therefore, it is necessary to discover new therapeutic targets for LUSC and provide patients with more treatment options. By analyzing different databases and tissue microarray immunohistochemistry staining, we firstly find that the expression of SRC/TOPK is elevated and positively correlated in LUSC and that patients with high SRC/TOPK expression have shorter survival time. Changing the expression levels of SRC/TOPK in LUSC cells can affect cell growth and colony formation, as there is a positive feedback loop between SRC and TOPK that regulates the transcription factor RB1, thereby altering the expressions of key factors in some growth-related signaling pathways. These inhibitors can synergistically promote apoptosis and have been validated in vivo. Therefore, the positive feedback loop between SRC and TOPK promotes tumorigenicity by inhibiting RB1 function, and has the potential to become a precise therapeutic target for LUSC, providing new possibilities for targeted therapy.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024188
DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the HPRT gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1’s regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024191
Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and in vivo experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261630
High altitude disease (HAD) arises from rapid ascent to elevations exceeding 2,500 m, where hypobaric hypoxia, cold, dryness, and intense ultraviolet radiation converge to produce a complex syndrome frequently manifesting as headache, dizziness, emesis, fatigue, and dyspnea; severe cases progress to high altitude pulmonary edema (HAPE) or high altitude cerebral edema. Epidemiological data indicate a combined HAD incidence of 37% in China, with acute high altitude disease (AHAD) alone reaching 40%, imposing a substantial public health burden. Conventional management relies on staged ascent, oxygen supplementation, and symptomatic pharmacotherapy, yet adverse effects and restricted applicability limit these interventions. Rhodiolae Crenulatae Radix et Rhizoma, the dried root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used since the Eastern Han Dynasty and is classified in the Tibetan medical canon as one of the 'Three Auspicious Treasures.' Its phytochemical profile encompasses phenylethanoid glycosides, flavonoids, phenylpropanoids, volatile oils, and organic acids. Modern pharmacology confirms anti-inflammatory, anti-oxidative stress, anti-fatigue, programmed cell death-regulatory, glucose-lipid metabolic, and gut microbiota-modulatory activities. This review synthesizes recent mechanistic and clinical evidence, providing a reference for clinical translation of Rhodiola crenulata in HAD management.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21272
BACKGROUND: Patients with cervical spondylosis often exhibit varying kinematic abnormalities due to degenerative structural changes and biomechanical imbalances in the cervical spine. Although previous studies have compared specific kinematic parameters between healthy individuals and cervical spondylosis patients, research on coupled motions and their associated ratios remains limited. OBJECTIVE: To investigate changes in kinematic parameters in cervical spondylosis patients before and after Feng's spinal manipulation therapy. METHODS: Thirty patients with cervical spondylosis and 30 healthy controls were enrolled. Participants completed three standardized motion tasks: lateral flexion, flexion-extension, and axial rotation. Three-dimensional cervical spine kinematics were quantified using stereophotogrammetry upon admission and discharge. The following kinematic parameters were analyzed: primary range of motion, coupled motion range, coupled motion patterns, motion symmetry, motion smoothness, and motion velocity. RESULTS AND CONCLUSION: Compared with healthy controls, patients with cervical spondylosis showed significantly reduced maximal angles in lateral flexion, flexion-extension, and axial rotation (P < 0.05), and significantly increased ratios of coupled flexion-extension during lateral flexion, coupled rotation during lateral flexion, coupled lateral flexion during extension, and coupled lateral flexion during rotation (P < 0.05). After treatment, patients showed significant improvements in visual analog scale score and cervical dysfunction index (P < 0.05). Significant differences were found in maximal lateral flexion angle, lateral flexion symmetry, maximum and average lateral flexion velocity, maximal flexion-extension angle, maximum and average flexion-extension velocity, maximal rotation angle, rotation symmetry, maximum rotation velocity, and average left rotation velocity before and after treatment (P < 0.05). No significant differences were observed in coupled motion patterns before and after treatment (P > 0.05). Significant differences were found in the ratios of coupled flexion-extension during right lateral flexion, coupled rotation during lateral flexion, coupled flexion-extension during right rotation, and coupled lateral flexion during rotation before and after treatment (P < 0.05). In conclusion, patients with cervical spondylosis exhibit increased ratios of some coupled motions relative to primary motions. Feng's spinal manipulation can significantly improve clinical symptoms and effectively restore cervical motor function.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21309
BACKGROUND: Upper limb rehabilitation robots have emerged as an indispensable component in global healthcare systems. Despite the extensive body of research in this field, which primarily focuses on areas such as development and application, there remains a significant need for comprehensive, systematic literature analysis to thoroughly examine the current research landscape, identify emerging hotspots, and predict future trends in this domain. OBJECTIVE: To conduct a visual analysis of research status, hotspots, and trends in the field of upper limb rehabilitation robots over the past decade using CiteSpace software, with the aim of identifying key research directions and providing intuitive references for researchers. METHODS: This study systematically retrieved literature related to upper-limb rehabilitation robotics from CNKI and the Web of Science Core Collection published between January 1, 2015, and March 13, 2025. CiteSpace 6.1.R1 software was employed for visualized analysis of included literature, covering key dimensions such as publication volume, authors, institutions, keywords, clusters, and bursts. RESULTS AND CONCLUSION: (1) A total of 1 054 articles were included, involving 659 authors. The United States held the highest overall ranking in terms of both research publication volume and centrality in this field. Among the contributing institutions, Northeast University and Univ Shanghai Sci&Technol ranked the highest in publication volume. Visualization analysis indicated an overall upward trend in upper limb rehabilitation robotics research, yet revealed limited collaboration among researchers and institutions. Main research directions included core technical methods, robot design and optimization, control strategies and algorithms, clinical application and evaluation, and emerging technologies and interdisciplinary integration. (2) Future research could focus on technological integration and intelligent upgrading, interdisciplinary collaborative innovation, and improvement of clinical applications to promote the continuous development and refinement of the upper limb rehabilitation robot field.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21310
BACKGROUND: Existing research on plantar fasciitis predominantly focuses on single techniques, short-term efficacy, pathogenesis, and diagnostic/evaluation studies. Systematic integration of global research trends and core hotspots is lacking. OBJECTIVE: To analyze the current status, hotspots, and trends in research on plantar fasciitis. METHODS: Search terms and free-text keywords related to plantar fasciitis were retrieved from PubMed to construct a search strategy. Relevant literature published between 1996 and 2025 was retrieved from the Web of Science Core Collection database. CiteSpace software, Excel, and Sci Explorer were used to perform co-occurrence analysis, salience analysis, and clustering analysis on countries, authors, institutions, disciplines, journals, keywords, and cited literature within this field. RESULTS AND CONCLUSION: A total of 1 606 articles were included in this visual analysis. The number of publications in plantar fasciitis research showed a fluctuating upward trend from 1996 to 2025. The United States was the most prolific country, contributing 423 articles (27.10% of the total). The institution with the highest output was Harvard University (USA) with 36 publications. The most prolific author was Landorf KB from La Trobe University with 33 publications. The most influential journal was Foot & Ankle International, with 112 articles and 950 total citations. The most influential paper was 'Shock Wave Therapy for Chronic Proximal Plantar Fasciitis'. In the field of plantar fasciitis, major treatment hotspots include extracorporeal shock wave therapy, platelet-rich plasma, and corticosteroid injections, but the long-term effectiveness, safety, cost, and standardized treatment protocols remain controversial and are current clinical research hotspots. In diagnosis, shear wave elastography is a hotspot for diagnostic evaluation, and more objective and quantitative diagnostic criteria are current research focuses. In mechanism exploration, research includes the biomechanical chain of vertical pressure transmission from hip-knee-ankle-foot and its influence on the occurrence of plantar fasciitis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21413
BACKGROUND: Recently, percutaneous minimally invasive pedicle screw fixation systems have become a popular treatment option for thoracolumbar fractures due to ongoing innovation in orthopedic internal fixation devices. Currently, while many studies compare the effectiveness of open pedicle screw fixation through or across the fractured vertebra, fewer studies compare these two methods when using navigation-assisted percutaneous minimally invasive techniques. OBJECTIVE: To compare the clinical efficacy of percutaneous minimally invasive pedicle screw fixation in the treatment of thoracolumbar fracture through and across the injured vertebra. METHODS: A retrospective analysis was performed on 67 patients with single level thoracolumbar fracture without spinal cord nerve injury who were treated in the Department of Spine Surgery, Affiliated Hospital of Yan'an University from October 2021 to June 2023. All of them were treated with percutaneous pedicle screw fixation with the assistance of computer navigation, and were followed up to 6 months after surgery. The injured vertebrae were divided into transinjured vertebrae group (n=35) and cross-injured vertebrae group (n=32). RESULTS AND CONCLUSION: ① There were no significant differences in preoperative general data between the two groups (P > 0.05), indicating comparability. ② Intragroup comparison: In both groups, the anterior vertebral height ratio, Cobb angle, visual analog scale score, and Oswestry disability index at 7 days and 6 months after surgery were significantly improved compared with preoperative values (P < 0.05). ③ Intergroup comparison: The operation time, intraoperative blood loss, incision length, and intraoperative fluoroscopy times in the cross-injured vertebrae group were significantly less than those in the trans-injured vertebrae group (P < 0.05), while there was no significant difference in hospital stay between the two groups (P > 0.05). At 7 days and 6 months after surgery, there were no significant differences in anterior vertebral height ratio, Cobb angle, visual analog scale score, and Oswestry disability index between the two groups (P > 0.05). ④ It is suggested that for patients with single-level thoracolumbar fractures without spinal cord nerve injury, compared with trans-injured vertebra fixation, percutaneous minimally invasive pedicle screw fixation across the injured vertebra has advantages of shorter operation time, less bleeding, smaller surgical incision, and fewer fluoroscopy times. In the medium-term follow-up period, both trans-injured and cross-injured percutaneous minimally invasive fixation can effectively restore and maintain the height of the injured vertebra, correct kyphotic deformity, rebuild spinal stability, and relieve pain, achieving excellent clinical results. For patients with AO type A thoracolumbar fractures with normal body mass index, without spinal cord nerve injury and posterior ligamentous complex injury, the less traumatic cross-injured vertebra percutaneous pedicle screw fixation is recommended.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21330
BACKGROUND: Studies showed that multiple myeloma microenvironment has the function of inducing mesenchymal stem cells to become senescent phenotype, while the effect of senescent bone marrow mesenchymal stem cells on multiple myeloma cells is rarely reported. OBJECTIVE: To investigate the effect of senescent bone marrow mesenchymal stem cells on the proliferation of multiple myeloma cells through paracrine galectin-3. METHODS: Bone marrow blood was collected from healthy donors, and bone marrow mesenchymal stem cells were extracted by Ficoll density gradient centrifugation and adherent purification. The third-generation bone marrow mesenchymal stem cells were taken and induced with 200 µmol/L hydrogen peroxide solution for 2 h, then cultured with L-DMEM complete medium for 24 h to construct a senescent bone marrow mesenchymal stem cell model. The model was identified by β-galactosidase staining and senescence gene P21 expression. RT-qPCR was used to detect the expression of galectin-3 in senescent bone marrow mesenchymal stem cells. The supernatant of senescent bone marrow mesenchymal stem cells was collected and concentrated by centrifugation to prepare conditioned medium, which was used to culture multiple myeloma cell line U266 for 24 h. CCK-8 was used to detect U266 cell proliferation, flow cytometry was used to detect U266 cell apoptosis, and RT-qPCR and western blot were used to detect BCL-2 protein and mRNA expression in U266 cells. Bone marrow from multiple myeloma patients and healthy individuals was collected, and galectin-3 levels were detected by ELISA. RESULTS AND CONCLUSION: After hydrogen peroxide induction, the number of β-galactosidase positive cells significantly increased, and the mRNA expression of P21 and galectin-3 was upregulated (P < 0.01). Compared with the control group, after culturing U266 cells with senescent bone marrow mesenchymal stem cell conditioned medium for 24 h, cell proliferation increased (P < 0.05), apoptosis rate decreased (P < 0.05), and BCL-2 protein and mRNA expression levels increased (P < 0.05). The level of galectin-3 in bone marrow of multiple myeloma patients was significantly higher than that of healthy individuals (P < 0.05). The results indicate that senescent bone marrow mesenchymal stem cells may promote the proliferation of multiple myeloma cells by upregulating BCL-2 expression through paracrine galectin-3.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21503
OBJECTIVE: To systematically evaluate and quantify the effects of different doses of aquatic exercise on muscle strength in healthy older adults using a Bayesian model-based dose-response meta-analysis, thereby determining the optimal exercise regimen and providing evidence-based recommendations for precise exercise prescription. METHODS: A systematic search was conducted in both English and Chinese databases, including PubMed, Embase, Web of Science, CNKI, and WanFang, to identify randomized controlled trials published up to March 2025 that investigated the effects of aquatic exercise on muscle strength in older adults. Data analysis was performed using R 4.5.0. A conventional meta-analysis was first conducted to estimate the overall effect, followed by a Bayesian model-based dose-response meta-analysis to quantify the nonlinear relationships between different exercise dose dimensions (frequency, session duration, weekly total duration, period, and intensity) and muscle strength improvement. The standardized mean difference (SMD) with 95% confidence interval (CI) was used as the effect size. RESULTS: A total of 13 randomized controlled trials involving 531 participants were included. The overall meta-analysis showed that aquatic exercise significantly improved muscle strength in older adults compared with control (SMD=0.56, 95%CI 0.39-0.74, P < 0.0001). Dose-response analysis revealed cumulative trends for training period, frequency, and weekly total duration: the effect peaked at 24 weeks (SMD=0.65, 95%CI 0.40-0.66); significant gains were achieved at a frequency of twice per week (SMD=0.56, 95%CI 0.22-0.58), with a slight increase at three times (SMD=0.62, 95%CI 0.24-0.62); weekly cumulative duration showed significant effects at 100 minutes (SMD=0.58, 95%CI 0.34-0.60) and plateaued after 200 minutes. In contrast, session duration and intensity exhibited an inverted U-shaped relationship: the effect peaked at 40 minutes per session (SMD=0.62, 95%CI 0.32-0.82), with an optimal range of 30-45 minutes; the optimal intensity was Borg RPE 10-12 (SMD=0.45, 95%CI 0.18-0.46), with diminishing returns beyond this range. CONCLUSION: Aquatic exercise is an effective strategy for improving muscle strength in healthy older adults. It is recommended that older adults engage in aquatic exercise two to three times per week, with each session lasting approximately 40 minutes, at a moderate-to-vigorous intensity (Borg RPE 10-12), and as a long-term strategy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21499
BACKGROUND: Increasing evidence has demonstrated the crucial role of synovial cell-chondrocyte signaling crosstalk mediated by synovial fluid exosomes in knee osteoarthritis. The signaling interaction between synovial cells and chondrocytes reveals, at the molecular level, the bidirectional regulatory role of synovial fluid exosomes in the progression of knee osteoarthritis. OBJECTIVE: To comprehensively interpret the interactions between synoviocytes and chondrocytes mediated by synovial fluid exosomes from multiple perspectives and levels to provide new insights and directions for research and clinical applications in the related field. METHODS: A literature search was conducted in PubMed for publications from January 2001 to June 2025 using the keywords “osteoarthritis*, exosomes, synovial cells, chondrocytes.” All relevant original studies, reviews, and clinical trials published from January 2001 to June 2025 were included, while irrelevant mechanisms and low-relevance studies were excluded. Finally, 93 articles were selected for comprehensive analysis. RESULTS AND CONCLUSION: During the development and progression of knee osteoarthritis, synovial cells and chondrocytes establish close signal communication via synovial fluid exosomes. This signaling interaction significantly affects the progression of knee osteoarthritis, potentially exacerbating cartilage degeneration and synovial inflammation, while also exerting protective regulatory effects under specific conditions. Therefore, the dual nature of this mechanism highlights the necessity for precise intervention, and targeting key molecules in exosome-mediated intercellular signaling pathways may offer new therapeutic strategies and targets for knee osteoarthritis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21501
BACKGROUND: Piezo-type mechanosensitive ion channel components (PIEZO) play a crucial role in cartilage degeneration, inflammation, and pain in osteoarthritis by sensing mechanical stimulation and regulating calcium signaling, potentially serving as an important therapeutic target for osteoarthritis. OBJECTIVE: To systematically review the role of PIEZO ion channels in the pathological mechanisms of osteoarthritis and evaluate their potential as a novel therapeutic target. METHODS: The first author searched CNKI and PubMed databases using Chinese and English search terms including "mechanical stress, Piezo, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial cell, immune cell" and "Piezo1, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial membrane, immune cell, GsMTx4" respectively. Literature published from 2000 to 2025 was selected, and 102 articles were finally included for review. RESULTS AND CONCLUSION: Mechanical stress plays a central role in the degeneration of articular cartilage and surrounding tissues. Chronic excessive mechanical stress or unbalanced loading causes chondrocyte damage, apoptosis, and inflammatory responses, thereby accelerating osteoarthritis progression. Known mechanosensors include transient receptor potential channel family, two-pore domain potassium channel family, degenerin/epithelial sodium channel family, and integrin family. PIEZO family is the first group of mechanosensitive cation channel pore proteins discovered in mammalian cells, widely present in human cells, sensing changes in ambient pressure to control Ca2+ influx and thus affect cellular functions. PIEZO ion channels regulate Ca2+ influx by sensing mechanical stimulation of the cell membrane, thereby influencing chondrocytes, osteogenesis, synovial cells, immune cells, and pain perception. Inhibiting PIEZO ion channels may become an effective method for treating arthritis.