Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03855-5
Background Hematopoietic stem and progenitor cells (HSPCs) mobilize from bone marrow to peripheral blood in response to stress. The impact of alloresponse-induced stress on HSPCs mobilization in human liver transplantation (LTx) recipients remains under-investigated.
Methods Peripheral blood mononuclear cell (PBMC) samples were longitudinally collected from pre- to post-LTx for one year from 36 recipients with acute rejection (AR), 74 recipients without rejection (NR), and 5 recipients with graft-versus-host disease (GVHD). 28 PBMC samples from age-matched healthy donors were collected as healthy control (HC). Multi-color flow cytometry (MCFC) was used to immunophenotype HSPCs and their subpopulations. Donor recipient-distinguishable major histocompatibility complex (MHC) antibodies determined cell origin.
Results Before LTx, patients who developed AR after transplant contained more HSPCs in PBMC samples than HC, while the NR group patients contained fewer HSPCs than HC. After LTx, the HSPC ratio in the AR group sharply decreased and became less than HC within six months, and dropped to a comparable NR level afterward. During the one-year follow-up period, myeloid progenitors (MPs) biased differentiation was observed in all LTx recipients who were under tacrolimus-based immunosuppressive treatment. During both AR and GVHD episodes, the recipient-derived and donor-derived HSPCs mobilized into the recipient’s blood-circulation and migrated to the target tissue, respectively. The HSPCs percentage in blood reduced after the disease was cured.
Conclusions A preoperative high HSPC ratio in blood characterizes recipients who developed AR after LTx. Recipients exhibited a decline in blood-circulating HSPCs after transplant, the cells mobilized into the blood and migrated to target tissue during alloresponse.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
YY1 is a crucial transcription factor and plays significant roles in biological processes. However, the mechanisms of YY1 action in ischemia-reperfusion injury and its regulatory role in ferroptosis have not been extensively studied. This study aims to elucidate the molecular mechanism by which NEDD4L-mediated degradation of YY1 through ubiquitination suppresses SLC7A11 transcription, leading to the promotion of cellular ferroptosis and exacerbation of hepatic ischemia-reperfusion injury (IRI), via the integration of multiple omics sequencing datasets. An IRI-I/R mouse model is established, followed by proteomic sequencing to identify proteins that are differentially expressed during IRI. The altered expression of YY1 is validated, and in vivo and in vitro experiments are used to assess its impact on IRI damage. The E3 ligase NEDD4L, which regulates YY1 ubiquitination, is identified and validated via the UbiBrowser 2.0 database. The ubiquitination types of YY1 and its sites are screened and confirmed through in vitro experiments. Transcriptional sequencing of YY1-overexpressing cell lines is conducted to analyze the involvement of the downstream transcription factor SLC7A11 in IRI, followed by validation of its regulatory role. The results show that YY1 is downregulated in liver tissues during IRI and is expressed primarily in liver cells. YY1 overexpression alleviates liver tissue and liver cell IRI both in vitro and in vivo. Upregulation of E3 ligase expression during IRI promotes the K63-linked ubiquitination of YY1 at the K339 site, leading to proteasomal degradation of YY1. RNA-seq analysis and experimental validation demonstrate that YY1 suppresses IRI-induced ferroptosis via the transcriptional regulation of downstream target genes. YY1 positively regulates SLC7A11 transcription, inhibits IRI-induced ferroptosis and ameliorates liver injury. In summary, the E3 ubiquitin ligase NEDD4L facilitates YY1 protein degradation through ubiquitination, suppressing the transcription of the ferroptosis inhibitor SLC7A11, thus promoting IRI-related ferroptosis and exacerbating liver injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025098
Pathological myocardial hypertrophy, often caused by hypertension, is a well-established independent risk factor for heart failure. SBK3, a gene selectively expressed at relatively high levels in cardiac tissues, has an unclear functional role in the heart. This study is designed to examine the role of SBK3 in transverse aortic constriction (TAC)-induced heart failure, aiming to identify a novel mitochondrion-targeted therapeutic strategy for heart failure. The subcellular localization of SBK3 in adult rat cardiomyocytes is investigated by western blot analysis and immunofluorescence staining, which reveal that SBK3 is located in the mitochondria. Subsequent western blot analysis shows that SBK3 protein expression is downregulated under pathological hypertrophy. To assess the functional relevance of this observation, SBK3 is overexpressed both in vivo (via cardiac-specific AAV9-cTNT) and in vitro (via adenoviral transduction). In vitro, adenovirus-mediated overexpression of SBK3 significantly inhibits ANP and BNP expression and increases the Ca2+ transient amplitude in angiotensin II (Ang II)-induced hypertrophic cardiomyocytes. In vivo, cardiac-specific SBK3 overexpression using cTNT promoter-containing adeno-associated virus 9 inhibits TAC-induced cardiac hypertrophy and heart failure. Mechanistically, SBK3 exerts its cardioprotective effects by preserving the mitochondrial ultrastructure and regulating the balance of respiratory chain complexes. In addition, SBK3 modulates key regulators of mitochondrial dynamics, including fission and fusion proteins, thereby contributing to mitochondrial integrity and protection against pathological cardiac remodeling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025117
Hepatocellular carcinoma (HCC) represents a significant global health challenge due to its aggressive malignancy. Abnormal glycosylation is a frequent phenomenon in tumor cells and manifests as alterations in key cancer biomarkers. This phenomenon is driven primarily by changes in the expressions of glycosyltransferases. Our study focuses on GALNT7, a member of the GALNT glycosyltransferase family, which catalyzes the initiation of O-linked glycan synthesis by transferring N-acetylgalactosamine (GalNAc) to serine or threonine residues on target proteins. We observe that GALNT7 expression is notably increased in HCC tissues and is correlated with increased tumor cell invasion, migration, and proliferation, alongside with reduced apoptosis, both in vivo and in vitro. Further molecular analyses indicate that GALNT7 specifically modifies the O-glycosylation pattern of MUC13, thereby influencing the activation of the PI3K/AKT signaling pathway. Additionally, elevated GALNT7 level enhances resistance to lenvatinib-based chemotherapy regimens. Thus, GALNT7 is a critical regulator of oncogenic processes in HCC. Targeting the GALNT7-MUC13-PI3K/AKT axis represents a novel therapeutic strategy for combating HCC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024175
Myocardial hypertrophy (MH) is an important factor contributing to severe cardiovascular disease. Previous studies have demonstrated that specific deletion of the protein arginine methyltransferase 1 (PRMT1) leads to MH, but the exact mechanism remains unclear. Serine/arginine-rich splicing factor 1 (SRSF1) affects the development and progression of cardiovascular disease by selectively splicing downstream signaling proteins. The present study is designed to determine whether PRMT1 is involved in MH by regulating SRSF1 and, if so, to explore the underlying mechanisms. Adult male mice and H9C2 cardiomyocytes are treated with isoprenaline (ISO) to establish MH models. The expression levels of PRMT1 are significantly decreased in the ISO-induced MH models, and inhibiting PRMT1 worsens MH, whereas overexpression of PRMT1 ameliorates MH. SRSF1 serves as the downstream target of PRMT1, and its expression is markedly elevated in MH. Moreover, SRSF1 increases the mRNA expressions of CaMKIIδ A and CaMKIIδ B, decreases the mRNA expression of CaMKIIδ C by altering the selective splicing of CaMKIIδ, and further participates in MH. In addition, there is an interaction between PRMT1 and SRSF1, whereby PRMT1 reduces the phosphorylation level of SRSF1 via methylation, thus further altering its functional activity and eventually improving MH. Our present study demonstrates that PRMT1 relieves MH by methylating SRSF1, which is expected to provide a new theoretical basis for the pathogenic mechanism of MH and potential drug targets for reducing MH and associated cardiovascular disease.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024163
Human rhomboid family-1 (RHBDF1) gene is recognized as an oncogene involved in breast cancer development. Previous studies have indicated that RHBDF1 contributes significantly to endoplasmic reticulum (ER) protein homeostasis by stabilizing the binding immunoglobulin protein (BiP) and promoting the unfolded protein response (UPR). Here, we report a relationship between RHBDF1 and the ER stress sensors PERK, IRE1, and ATF6. We show that RHBDF1 deficiency in breast cancer cells results in decreased levels of PERK, pPERK, and peIF2α. These protein levels can be restored in RHBDF1-deficient breast cancer cells by artificial overexpression of RHBDF1 but not IRE1 or ATF6. Additionally, we show that the transcription factor FoxO3 is essential for the RHBDF1-mediated production of PERK. Subsequent analysis reveals that RHBDF1 activates JNK, which causes FoxO3 to translocate into the cell nucleus. These findings demonstrate that RHBDF1 supports the UPR by upregulating the PERK/peIF2α pathway via the JNK/FoxO3 axis and that the functions of RHBDF1 are essential for preserving the homeostasis of ER proteins.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21416
BACKGROUND: Non-infectious poor wound healing following lumbar surgery is a significant clinical complication that prolongs hospitalization and increases the risk of reoperation. However, its predictive indicators remain unclear. Based on the hypothesis that paraspinal muscle degeneration may impede tissue repair by altering the local microenvironment, this study aimed to investigate the predictive value of preoperative paraspinal muscle fatty infiltration for non-infectious poor wound healing and its association with osteoporosis. OBJECTIVE: To quantify the degree of paraspinal muscle fatty infiltration using preoperative MRI and evaluate its predictive value for non-infectious poor wound healing after lumbar surgery. METHODS: A retrospective analysis was conducted on medical records of 4,368 patients who underwent traditional open posterior lumbar surgery at Third Affiliated Hospital of Guangzhou University of Chinese Medicine between 2019 and 2024. We screened 190 patients with a postoperative hospital stay of 15 days or longer. Based on postoperative wound healing and infection indicators, 41 patients with non-infectious poor healing were selected as the poor healing group. From the remaining 4,178 patients, 40 patients with good healing were selected as the good healing group. The poor healing group was further subdivided into osteoporosis and non-osteoporosis subgroups. Preoperative lumbar MRI images were collected, and Image J software was used to measure the cross-sectional area of the psoas major muscle and the percentage of fat infiltration in the erector spinae and multifidus muscles. RESULTS AND CONCLUSION: (1) There were no significant differences in gender, age, or diabetes between the poor healing and good healing groups (P > 0.05). (2) The functional cross-sectional area and fat infiltration percentage of the psoas major, erector spinae, and multifidus muscles were significantly different between the two groups (P < 0.05). (3) Logistic regression analysis showed that fat infiltration percentage was an independent risk factor for poor wound healing. (4) Receiver operating characteristic curve analysis showed that fat infiltration percentage had high predictive value for poor wound healing (area under the curve > 0.7). (5) One-way ANOVA indicated that osteoporosis was a risk factor for fat infiltration in the L4 multifidus muscle (P < 0.05). (6) The results indicate that paraspinal muscle fat infiltration percentage is an important predictor of non-infectious poor wound healing after traditional open posterior lumbar surgery, providing clinical reference. Osteoporosis was also confirmed as a risk factor for L4 multifidus fat infiltration, but due to the small subgroup sample size, whether osteoporosis affects non-infectious poor healing after lumbar surgery requires further clinical trials.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21370
BACKGROUND: In recent years, metabolic disorders have been confirmed to be closely related to the onset of osteoarthritis, but the causal relationship between plasma metabolites and osteoarthritis has not been systematically elucidated. OBJECTIVE: To explore the causal relationship between 1,400 plasma metabolites and 9 types of osteoarthritis using two-sample Mendelian randomization. METHODS: A genome-wide association study of 1,400 metabolites was used as the exposure. Nine types of arthritis, namely any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, hip osteoarthritis, spinal osteoarthritis, finger osteoarthritis, hand osteoarthritis, and thumb osteoarthritis, were set as the outcomes. Single nucleotide polymorphisms were used as instrumental variables, and sensitive single nucleotide polymorphisms were selected for Mendelian randomization analysis. The inverse variance weighted method was used as the main analysis approach. Meanwhile, four methods, namely MR-Egger, weighted median, simple mode, and weighted mode, were employed for cross-validation. MR-PRESSO, Cochran's Q test, and other methods were used for sensitivity and pleiotropy analyses. The false discovery rate method was used for further correction. RESULTS AND CONCLUSION: Mendelian randomization analysis showed that finger osteoarthritis, hand osteoarthritis, hip osteoarthritis, and spinal osteoarthritis had no results meeting FDR < 0.05. Any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, and thumb osteoarthritis were significantly causally associated with multiple metabolites. Metabolites such as glycine, serine, higenamine, and sulfate were closely related to multiple osteoarthritis types. Compared with some non-weight-bearing joint osteoarthritis (e.g., finger and hand osteoarthritis), plasma metabolites showed stronger sensitivity with weight-bearing joint osteoarthritis (e.g., knee and hip osteoarthritis). This study provides a theoretical basis for metabolic intervention strategies for osteoarthritis in the Chinese population and offers a methodological paradigm for mechanistic research on complex diseases in China.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21319
BACKGROUND: Protocatechualdehyde has the potential to delay the progression of atherosclerosis. Nevertheless, its specific mechanisms of action within multi-target regulatory networks remain unclear and require further investigation. OBJECTIVE: To investigate the potential targets of protocatechualdehyde in intervening atherosclerosis based on transcriptomics. METHODS: (1) Thirty ApoE-/- mice were randomly divided into a model group (n=10), a rosuvastatin group (n=10), and a protocatechualdehyde group (n=10). An atherosclerosis model was induced by feeding the mice with a high-fat diet for 12 weeks. Seven C57BL/6J mice were selected as a control group (without modeling). After successful modeling, the control group and model group were given physiological saline by gavage; the rosuvastatin group was given rosuvastatin by gavage, and the protocatechualdehyde group was given protocatechualdehyde by gavage, once a day for 12 consecutive weeks. After the last administration, samples were collected. Serum lipid levels were measured using an automatic biochemical analyzer. Aortic plaque pathology was assessed by gross oil red O staining, hematoxylin-eosin staining, and Masson staining of aortic root paraffin sections. (2) High-throughput sequencing was used to analyze the transcriptome expression profiles of aortic samples from the control, model, and protocatechualdehyde groups. Differential gene screening (FC > 2, q < 0.05), GO and KEGG enrichment analyses, weighted gene co-expression network analysis, and short time-series expression miner analysis were performed based on the Ouyi Cloud platform. A protein-protein interaction network was constructed using the STRING database, and core genes were screened using Cytoscape. (3) RT-PCR was used to detect the mRNA expression of Calm4 (calmodulin pseudogene 4), Kprp (keratinocyte proline-rich protein), Hrnr (filaggrin 2), and Lor (loricrin) in aortic samples from the control, model, and protocatechualdehyde groups to validate candidate targets. RESULTS AND CONCLUSION: (1) Protocatechualdehyde significantly reduced serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels in atherosclerotic mice. Gross oil red O staining and hematoxylin-eosin and Masson staining of aortic root paraffin sections showed that protocatechualdehyde reduced plaque formation, inhibited intimal thickening, increased collagen fiber content in plaques, and stabilized plaques. (2) Transcriptome analysis identified 191 differentially expressed genes, and Cytoscape analysis preliminarily identified Kprp, Calm4, Hrnr, and Lor as key candidate targets. (3) RT-PCR showed that the mRNA expression of Kprp, Calm4, Hrnr, and Lor in the model group was higher than that in the control group (P < 0.05), while the mRNA expression of Kprp, Calm4, and Lor in the protocatechualdehyde group was lower than that in the model group (P < 0.05). These results indicate that protocatechualdehyde intervention can significantly improve atherosclerotic plaques, and Kprp, Calm4, and Lor may be potential targets for protocatechualdehyde in the treatment of atherosclerosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21387
BACKGROUND: The magnetic field mitochondrial regulation technology has been proven to enhance skeletal muscle function. Low-load blood flow restriction training can effectively induce adaptive growth of muscle strength through metabolic emergency mechanisms. Currently, both technologies have become hotspots in the application and research of skeletal muscle function improvement and treatment. However, the differences in their effects on muscle strength enhancement and whether their combined application can produce a synergistic effect remain unclear. OBJECTIVE: To observe the differences in the effects of low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) and low-load blood flow restriction training on muscle strength enhancement and the impact of their combined intervention on lower limb muscle strength. METHODS: Fifty-six healthy subjects were recruited and randomly divided into magnetic stimulation group (high-load squat training + magnetic stimulation), blood flow restriction group (low-load blood flow restriction squat training), combined group (low-load blood flow restriction squat training + magnetic stimulation), and control group (high-load squat training). The trial lasted 4 weeks, with training three times per week, and low-frequency pulsed magnetic stimulation (1.5 mT, 3 300 Hz) was administered every 48 hours. After the trial, changes in maximal strength, explosive power, and strength endurance of the lower limb muscles were observed among groups. RESULTS AND CONCLUSION: Fifty subjects completed the trial and were included in the analysis. ① After 4 weeks of intervention, the maximal strength, explosive power, and strength endurance of the lower limbs in the magnetic stimulation, blood flow restriction, and combined groups significantly increased. ② In terms of maximal strength increase, blood flow restriction was superior to magnetic field mitochondrial regulation technology; low-load blood flow restriction also enhanced distal muscle strength, while magnetic field mitochondrial regulation technology had the advantage of improving maximal strength without fatigue accumulation. ③ In terms of explosive power increase, both technologies had similar effects; magnetic stimulation was more advantageous for explosive power in single-joint movements, while low-load blood flow restriction training was more advantageous for explosive power in multi-joint coordinated movements. ④ In terms of strength endurance increase, magnetic stimulation technology, due to its mitochondrial function regulation, effectively improved muscle fatigue resistance. The results suggest that the combined application of magnetic stimulation and low-load blood flow restriction can produce synergistic effects on maximal strength, explosive power, and strength endurance of the lower limbs. This technical approach may provide a novel and efficient auxiliary training protocol for lower limb muscle strength enhancement in postoperative rehabilitation and sports injury patients who cannot undergo high-intensity resistance training.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21456
BACKGROUND: Existing treatments can effectively reduce fracture risk in patients with osteoporosis, but their effectiveness is limited in patients with concurrent inflammatory diseases (such as rheumatoid arthritis) or severe postmenopausal osteoporosis. Therefore, the development of novel therapeutic strategies with both anti-inflammatory and anti-osteoclast properties is of great clinical significance. OBJECTIVE: To develop an innovative Sr²⁺ and bromodomain inhibitor Birabresib-loaded nanocomposite material (Bir@Sr-MBG) and characterize their cytocompatibility and in vitro immunomodulatory, anti-osteoclast differentiation, and osteoclast differentiation-promoting effects. METHODS: (1) Strontium-bioactive glass (Sr-MBG) was synthesized using a modified microemulsion-assisted sol-gel method. Birabresib was loaded into the mesoporous structure of Sr-MBG using an optimized solution adsorption method. The resulting material, designated Bir@Sr-MBG, was characterized for drug encapsulation efficiency, drug loading rate, and in vitro drug release. (2) Primary mouse bone marrow macrophages were cultured with different concentrations of Birabresib or Bir@Sr-MBG, and cytocompatibility was assessed by CCK-8 assay. (3) For immunomodulation, cells were divided into five groups: control, lipopolysaccharide (LPS), LPS+Sr-MBG, LPS+Birabresib, and LPS+Bir@Sr-MBG. After 24 h incubation, immunofluorescence staining for iNOS (M1 marker) and CD206 (M2 marker) was performed; qPCR and ELISA were used to measure expression of IL-1β, IL-6, TNF-α, and IL-4. (4) For osteoclast differentiation, bone marrow macrophages were induced with RANKL and divided into four groups: control, Sr-MBG, Birabresib, and Bir@Sr-MBG. After 5 days, TRAP staining, cytoskeletal staining, and scanning electron microscopy were performed; qPCR was used to measure osteoclast-related genes (CTSK, c-Fos, TRAP, NFATc1). (5) For osteogenic differentiation, rat bone marrow mesenchymal stem cells were cultured in osteogenic medium and divided into five groups: control, LPS, LPS+Sr-MBG, LPS+Birabresib, and LPS+Bir@Sr-MBG. After 7 days, alkaline phosphatase and alizarin red staining were performed; qPCR was used to measure osteogenic genes (ALP, Runx2, OCN, OPN). RESULTS AND CONCLUSION: (1) The drug encapsulation efficiency of Bir@Sr-MBG was 44.82%, drug loading rate was 7.47%, and sustained release of Birabresib was observed for over 168 h. (2) CCK-8 assay showed good cytocompatibility for Birabresib at 0.1-1 μg/mL and Bir@Sr-MBG at 20-200 μg/mL. (3) Immunofluorescence staining showed that Bir@Sr-MBG improved the inflammatory microenvironment by regulating macrophage polarization, with stronger anti-inflammatory effects than Sr-MBG or Birabresib alone. qPCR and ELISA confirmed that Bir@Sr-MBG downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and upregulated anti-inflammatory cytokine (IL-4) more effectively than Sr-MBG or Birabresib. (4) TRAP staining, cytoskeletal staining, SEM, and qPCR showed that Bir@Sr-MBG had stronger anti-osteoclast differentiation effects than Sr-MBG or Birabresib. (5) ALP staining, alizarin red staining, and qPCR showed that under inflammatory conditions, Bir@Sr-MBG promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells more effectively than Sr-MBG or Birabresib. (6) These results indicate that Bir@Sr-MBG effectively regulates bone metabolism and improves the bone microenvironment through a dual mechanism, showing significant therapeutic potential for osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21477
BACKGROUND: Hernandezine has shown promising therapeutic effects due to its anti-inflammatory bioactivity in diseases such as suppression of tumors, antiplatelet agglutination and diabetes. However, there are no basic studies on the effects and molecular mechanism of Hernandezine on macrophage phenotype and osteoclast activation. OBJECTIVE: To investigate the role of Hernandezine on the regulation of macrophage polarization, osteoclast activation and osteoporosis. METHODS: (1) Cellular experiments: RAW264.7 was used as macrophage model and divided into four groups: Control group, lipopolysaccharide group, lipopolysaccharide + 2.5 μmol/L Hernandezine group, lipopolysaccharide + 5 μmol/L Hernandezine group. Macrophage polarization was induced in the latter three groups using a complete medium supplemented with lipopolysaccharide. The two drug-treated groups received 2.5 and 5 μmol/L Hernandezine, respectively. RAW264.7 cells were induced toward osteoclast differentiation using a complete medium supplemented with nuclear factor κB receptor activator ligand. Macrophage polarization was assessed via qRT-PCR and immunofluorescence for inflammatory cytokine expression. The effects of Hernandezine on osteoclast differentiation were evaluated using qRT-PCR, tartrate-resistant acid phosphatase staining, and F-actin staining. (2) In vivo experiments: Twenty-four female C57BL/6J mice were randomly divided into four groups: sham operation, ovariectomy, ovariectomy + 5 mg/kg Hernandezine, and ovariectomy + 10 mg/kg Hernandezine. The latter three groups underwent bilateral ovariectomy to establish an osteoporosis model. The two drug-treated groups received intraperitoneal injections of Hernandezine at 5 or 10 mg/kg every two days post-surgery. After 8 weeks, femurs were collected for Micro-CT scanning, bone parameter analysis, and hematoxylin-eosin staining to evaluate bone loss. RESULTS AND CONCLUSION: Hernandezine inhibited lipopolysaccharide-induced pro-inflammatory gene expression in macrophages by downregulating the transcription of Toll-like receptor 4/nuclear factor κB signaling pathway-related genes, exhibiting a concentration-dependent effect, with 5 μmol/L showing more significant inhibition. Hernandezine also inhibited the expression of genes related to osteoclast activation and bone resorption, and suppressed osteoclast activation in vitro in a concentration-dependent manner. In vivo, Hernandezine reduced bone loss in estrogen-deficient osteoporotic mice, with the 10 mg/kg group showing better recovery. CONCLUSION: This study confirms that Hernandezine inhibits macrophage pro-inflammatory phenotype transformation and osteoclast activation by downregulating the Toll-like receptor 4/nuclear factor κB signaling pathway, and alleviates excessive bone loss in estrogen-deficient osteoporosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21515
BACKGROUND: Ulnar impaction syndrome is a common wrist disorder, and ulnar shortening osteotomy is one of the definitive surgical interventions for its treatment. Although various ulnar shortening osteotomy techniques exist, numerous clinical comparative studies have focused on pairwise comparisons, while biomechanical simulations comparing the efficacy of different osteotomy methods via finite element analysis remain unreported. OBJECTIVE: To simulate and compare the biomechanical characteristics of ulnar impaction syndrome under different osteotomy treatment modalities employing finite element method so as to provide references and evidence for clinical decision-making. METHODS: CT data of the intact ulna and radius from a healthy adult male volunteer were utilized. Modeling and finite element software platforms — Mimics 19.0, Geomagic Studio 2013, SolidWorks 2019, and Ansys 17.0 — were sequentially applied to construct five ulnar osteotomy models: (1) distal ulnar V-shaped osteotomy; (2) distal ulnar transverse osteotomy; (3) ulnar metaphyseal transverse osteotomy; (4) distal ulnar trapezoidal osteotomy; (5) distal ulnar oblique osteotomy. According to the experimental design and internal fixation principles, plates and screws were assembled. Subsequently, three motion modes of wrist joint axial compression, pronation, and supination were simulated, and corresponding boundary conditions and loads were applied to each group to obtain stress distribution and displacement at the osteotomy site and internal fixation devices. Finally, the results were compared with established experimental data standards to draw relevant conclusions. RESULTS AND CONCLUSION: (1) Under three different motions and loads, the five different ulnar shortening osteotomy methods all maintained stable osteotomy ends without significant relative differences. (2) There were certain differences in the stress and deformation of internal fixation devices among the five methods under three simulated motion states: under simulated pronation, the internal fixation plate of ulnar metaphyseal transverse osteotomy was at risk of fracture; under simulated supination, the plate also exhibited deformation risk. (3) Regarding stress and displacement of internal fixation, the distal ulnar V-shaped osteotomy showed relative advantages in stability under all three simulated states.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21526
BACKGROUND: Magnetic mitochondrial calcium regulation technology, as a non-invasive method for promoting skeletal muscle function, has been effectively demonstrated in improving muscle function and enhancing metabolic sensitivity. Existing studies have shown that this technology has significant physiological promoting effects on adults, the elderly, and postoperative rehabilitation populations, but its intervention effects on skeletal muscle function and body composition in adolescents aged 12-13 years remain unclear. OBJECTIVE: To investigate the sensitivity of skeletal muscle function and body composition to magnetic stimulation in adolescents aged 12-13 years by evaluating these parameters. METHODS: A total of 34 junior high school students from Liaoning Experimental School were recruited and randomly divided into a control group and an experimental group. The control group maintained routine campus activities without a specific physical training program. The experimental group additionally received low-frequency pulsed magnetic field intervention twice a week (stimulation duration 10 min, magnetic field intensity 1.5 mT, frequency 3300 Hz, with an interval of 72 h between interventions) for 4 consecutive weeks. Before (pre-test) and after (post-test) the intervention, changes in maximum strength, explosive power, endurance quality, and body composition indicators of the intervention site were observed. RESULTS AND CONCLUSION: After 4 weeks of 8 sessions of low-frequency pulsed magnetic field stimulation, the participants' explosive power, aerobic endurance, muscle isometric endurance, and body composition indicators were significantly improved, indicating that adolescents aged 12-13 years have good magnetic calcium-regulated stimulation sensitivity for the above skeletal muscle functions and body composition. In terms of maximum strength improvement, the effect was not significant, and their muscle magnetic sensitivity was lower than that of adults, but it had certain advantages in maintaining maximum strength under long-term sedentary conditions. The results indicate that magnetic calcium-regulated mitochondrial technology, as a novel passive, non-invasive skeletal muscle function promotion technique, can be attempted as a new intervention means to improve adolescent physical health.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21595
BACKGROUND: Neuropathic pain is a chronic pain condition caused by direct damage or functional abnormalities in the somatic sensory nervous system. Its clinical manifestations include spontaneous pain and tactile hypersensitivity, which are difficult to control effectively with traditional drug therapies. The pathogenesis of neuropathic pain involves multiple physiological processes, including neuronal hyperexcitability, glial cell activation, neurotransmitter imbalance, immune responses, and oxidative stress. Existing medications and invasive treatments often carry side effects and exhibit significant limitations in efficacy. Therefore, exploring safe and effective non-pharmacological interventions, particularly exercise-based interventions for improving neuropathic pain, has become a critical research focus in the field of neuropathic pain. OBJECTIVE: To review advances in understanding the mechanisms of neuropathic pain, analyze the potential and mechanisms of exercise intervention in alleviating neuropathic pain, demonstrate the clinical application prospects of exercise as a non-pharmacological intervention strategy, and emphasize future research directions. METHODS: PubMed and CNKI databases were searched using Chinese and English keywords including neuropathic pain, nerve injury pain, exercise, physical activity, aerobic exercise, resistance training, yoga, pathogenesis, inflammation, neurotransmitter, neurotrophin, oxidative stress, and rehabilitation. A total of 139 articles were included. The core mechanisms of neuropathic pain were analyzed, focusing on the multi-target and multi-pathway synergistic effects of exercise in alleviating neuropathic pain. RESULTS AND CONCLUSION: The pathogenesis of neuropathic pain involves neuronal hyperexcitability, glial cell activation, neurotransmitter imbalance, immune-inflammatory responses, and oxidative stress-induced nerve damage. Exercise intervention alleviates neuropathic pain by regulating neurotransmitter release, promoting neurotrophic factor expression, inhibiting inflammatory responses, and reducing oxidative stress. Specifically, exercise upregulates the expression of neurotrophic factors such as brain-derived neurotrophic factor and nerve growth factor, inhibits the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha, and further regulates core pathways in neuropathic pain development. Exercise also produces analgesic effects by modulating the endogenous opioid system. The specific mechanisms of different exercise types on neuropathic pain need further investigation, and personalized exercise prescription design and exercise parameter optimization face many challenges. Future research should focus on constructing and validating exercise prescriptions, clarifying the synergistic effects of exercise combined with drug therapy, to support the advancement of clinical treatment for neuropathic pain.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21576
BACKGROUND: Exercise therapy is a non-drug management strategy for diabetic patients and can significantly improve endothelial function. However, its effect on endothelial progenitor cells and its specific biological mechanism are still unclear. OBJECTIVE: To explore the effects of voluntary wheel running on the function of endothelial progenitor cells in type 2 diabetic rats and reveal the possible mechanisms of action. METHODS: (1) Animal experiment: Sixty Wistar rats were randomly divided into four groups. The control group (n=15) underwent neither modeling nor any exercise intervention. In the model group (n=15), a rat model of type 2 diabetes was established using a high-fat diet combined with streptozotocin induction, with no exercise intervention after modeling. In the model exercise group (n=15), model rats underwent voluntary wheel running for 5 days per week over 8 weeks. In the model exercise + gene silencing group (n=15), after establishing the type 2 diabetes model, rats received tail vein injection of insulin-like growth factor 1 receptor-specific small interfering RNA adenovirus recombinant, and 4 hours later underwent voluntary wheel running for 5 days per week over 8 weeks. After exercise intervention, fasting blood glucose, serum insulin-like growth factor 1 and insulin levels, and insulin resistance index were measured. Thoracic aortic endothelial diastolic function was assessed by in vitro vascular ring assay. (2) Cell experiment: After exercise intervention, bone marrow endothelial progenitor cells were isolated and cultured from each group. Cell proliferation, migration, and tube formation abilities were detected by MTT assay, scratch test, and Matrigel tube formation assay. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of insulin-like growth factor 1 receptor in cells. Western blot was used to detect the protein expression of insulin-like growth factor 1, insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B. RESULTS AND CONCLUSION: (1) Animal experiment: Compared with the control group, the model group showed increased fasting blood glucose, insulin levels, and insulin resistance index (P < 0.05), and decreased insulin-like growth factor 1 level (P < 0.05). Compared with the model exercise group, the model group and the model exercise + gene silencing group showed increased fasting blood glucose, insulin levels, and insulin resistance index (P < 0.05), and the model group showed decreased insulin-like growth factor 1 level (P < 0.05). The vascular endothelial diastolic function in the model group, model exercise group, and model exercise + gene silencing group was weaker than that in the control group (P < 0.05), and the model exercise group showed stronger vascular endothelial diastolic function than the model group and the model exercise + gene silencing group (P < 0.05). (2) Cell experiment: The proliferation, migration, and tube formation abilities of bone marrow endothelial progenitor cells and the mRNA expression of insulin-like growth factor 1 receptor in the model group were lower than those in the control group. The proliferation, migration, and tube formation abilities of bone marrow endothelial progenitor cells and the mRNA expression of insulin-like growth factor 1 receptor in the model exercise group were higher than those in the model group and the model exercise + gene silencing group (P < 0.05). The protein expression of insulin-like growth factor 1, insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B in the model group was lower than that in the control group (P < 0.05). The protein expression of insulin-like growth factor 1 receptor, phosphorylated phosphatidylinositol-3 kinase, and phosphorylated protein kinase B in the model exercise group was higher than that in the model group and the model exercise + gene silencing group (P < 0.05), and the protein expression of insulin-like growth factor 1 was higher than that in the model group (P < 0.05). (3) These results indicate that voluntary wheel running can improve the function of endothelial progenitor cells in type 2 diabetic rats, and the mechanism is related to the activation of the insulin-like growth factor 1 receptor-mediated phosphatidylinositol-3 kinase/protein kinase B signaling pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21581
BACKGROUND: In recent years, magnetic stimulation therapy can activate the classical transient receptor potential channel 1, triggering the calcium-mitochondrial axis to enhance myogenesis and mitochondrial biogenesis in vivo, thereby recapitulating physiological adaptations related to exercise-induced metabolic responses. As an emerging technique for promoting muscle function, magnetic stimulation has gained widespread attention and validation in the rehabilitation of muscular diseases due to its advantages of being non-invasive, passive, and safe. However, there is a lack of clinical studies on the therapeutic efficacy of this technique in the treatment of disuse-induced muscle atrophy. OBJECTIVE: To investigate the therapeutic effect of exercise therapy combined with magnetic stimulation on the recovery of muscle strength and locomotor ability in patients with disuse-induced muscle atrophy of the lower limbs. METHODS: Sixteen patients with lower limb disuse muscle atrophy caused by prolonged bed rest after unilateral Achilles tendon rupture surgery were recruited and randomly divided into control group and experimental group, 8 cases in each group. The control group received traditional exercise rehabilitation therapy, including joint range of motion training, muscle strength training, and soft tissue stretching training, 3 times a week. The experimental group additionally received medical magnetic physical factor stimulation (intensity 1.5 mT, frequency 3 300 Hz, 48 h per session, 10 min each time) on this basis, with a total trial duration of 4 weeks. All subjects underwent maximum voluntary contraction (MVC) test of the lower limbs and gait speed measurements including Timed Up and Go test (TUG), 5-times sit-to-stand test (5STS), and 6 m normal walking speed test before and after intervention. RESULTS AND CONCLUSION: After 4 weeks of intervention, all 16 subjects completed the trial. In the experimental group, the maximum voluntary contraction of the affected lower limb (P=0.001) and the difference rate of MVC between affected and healthy sides (P=0.001) significantly decreased, and the improvements were superior to those in the control group. In terms of gait speed indicators, the experimental group showed significant improvements in TUG (P=0.038), 6 m normal walking speed (P=0.025), and 5STS (P=0.050) compared with baseline. Between-group comparison revealed that the experimental group had significantly greater improvements in MVC of the affected leg (P=0.003), difference rate of MVC between affected and healthy sides (P=0.004), TUG (P=0.019), and 6 m normal walking speed (P=0.011) than the control group. These data confirm that after 4 weeks of low-frequency pulsed magnetic field (1.5 mT, 3 300 Hz) combined with exercise therapy, patients with disuse muscle atrophy after Achilles tendon rupture showed significantly better improvements in MVC of the affected and healthy legs, TUG, and 6 m normal walking speed than the control group, demonstrating that magnetic stimulation combined with exercise therapy has an auxiliary synergistic effect on isometric muscle strength and lower limb motor function. Therefore, magnetic stimulation combined with exercise therapy can be used as a new means for rehabilitation of disuse muscle atrophy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21561
BACKGROUND: Nimbolide, a triterpenoid bioactive compound, exhibits multiple biological activities including anti-inflammatory, antioxidant, antitumor, and antibacterial effects. However, its potential to alleviate osteoporosis by regulating osteoclast differentiation and apoptosis remains unreported. OBJECTIVE: To investigate the effects of nimbolide on osteoclast differentiation, osteoclast apoptosis, and osteoporosis. METHODS: (1) Cell experiments: Mouse bone marrow-derived macrophages were divided into four groups: the cells were cultured in α-MEM complete medium containing macrophage colony-stimulating factor in the control group; the cells were cultured in α-MEM complete medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand in the osteoclast induction group; the cells were cultured in osteoclast-inducing differentiation medium supplemented with 100 nmol/L or 200 nmol/L nimbolide, respectively in the low- and high-dose nimbolide groups. The effects of nimbolide on osteoclast differentiation and apoptosis were assessed using tartrate-resistant acid phosphatase staining, Annexin V-FITC/PI staining, and RT-qPCR. (2) In vivo experiments: Twenty-four 8-week-old female C57BL/6J mice were randomly divided into four groups: The mice in the sham group underwent only removal of periovarian fat; the model group underwent bilateral ovariectomy; the low- and high-dose nimbolide groups received intraperitoneal injections of 5 and 10 mg/kg nimbolide solution every 2 days after modeling. After 8 weeks of modeling, serum and femurs were collected for relevant assays. RESULTS AND CONCLUSION: (1) Cell experiments: RT-qPCR and tartrate-resistant acid phosphatase staining results showed that nimbolide inhibited the expression of osteoclast differentiation-related genes and suppressed osteoclast differentiation in vitro; RT-qPCR and Annexin V-FITC/PI staining results showed that nimbolide inhibited the expression of apoptosis-related genes and induced apoptosis of mature osteoclasts; RT-qPCR results showed that nimbolide promoted osteoclast apoptosis via the Fas/FasL signaling pathway, and the regulatory effects of nimbolide on osteoclast differentiation and apoptosis were concentration-dependent. (2) Animal experiments: Micro-CT and hematoxylin-eosin staining results showed that nimbolide reduced bone loss in estrogen deficiency-induced osteoporotic mice, with 10 mg/kg nimbolide showing better effects; nimbolide had no significant effect on serum estradiol levels in ovariectomized mice. These results indicate that in vitro experiments confirmed that nimbolide not only inhibits osteoclast differentiation but also promotes apoptosis of mature osteoclasts; in vivo experiments confirmed that nimbolide alleviates excessive bone loss in estrogen deficiency-induced osteoporotic mice.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025093
Hepatic ischemia-reperfusion injury (IRI) remains a major clinical challenge in liver transplantation and resection, with ferroptosis emerging as a critical cell death modality. This study investigates the mechanistic role of the transcription factor YY1 and its regulation by the E3 ubiquitin ligase NEDD4L in hepatic IRI. Using an established mouse IRI model and proteomic sequencing, YY1 was identified as significantly downregulated in injured liver tissues, predominantly in hepatocytes. In vivo and in vitro overexpression of YY1 attenuated IRI-induced liver damage and ferroptosis. Mechanistically, NEDD4L, an E3 ligase upregulated during IRI, was found to interact with YY1 and catalyze K63-linked ubiquitination at lysine 339, leading to proteasomal degradation of YY1. Transcriptomic analysis and validation revealed that YY1 positively regulates the transcription of SLC7A11, a key ferroptosis inhibitor. Consequently, NEDD4L-mediated degradation of YY1 suppresses SLC7A11 expression, promoting ferroptosis and exacerbating hepatic injury. These findings delineate a novel NEDD4L-YY1-SLC7A11 axis in IRI pathogenesis, offering potential therapeutic targets. The study acknowledges limitations, including the need for validation in human liver samples and further in vivo confirmation of some in vitro findings. This research provides a mechanistic framework for developing targeted interventions against hepatic IRI.