Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzae037
This is a correction to: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang, dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms, Genomics, Proteomics & Bioinformatics, Volume 20, Issue 3, June 2022, Pages 446–454, https://doi.org/10.1016/j.gpb.2022.04.006. The published version of this manuscript contained errors in the author affiliation listings. The corrected affiliations are as follows: Feng Xu1,#, Yifan Wang2,#, Yunchao Ling2, Chenfen Zhou2, Haizhou Wang1, Andrew E. Teschendorff3, Yi Zhao4, Haitao Zhao5, Yungang He6,*, Guoqing Zhang2,*, Zhen Yang1,* 1 Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 2 Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 6 Shanghai Fifth People’s Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China These details have been corrected only in this correction notice to preserve the published version of record.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04202-y
Background Severe hepatic steatosis can exacerbate Ischemia–reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI. Methods This study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs). Additionally, rat fatty Liver transplantation (LT) model, mouse fatty liver IRI model, and Steatotic Hepatocyte Hypoxia-Reoxygenation (SHP-HR) model were constructed. Extracellular vesicles derived from SS-USCs and RS-USCs were isolated and subjected to mass spectrometry analysis. The therapeutic effects of Spindle-shaped USCs Exosomes (SS-USCs-Exo) and Rice-shaped USCs Exosomes (RS-USCs-Exo) were explored, elucidating their potential mechanisms in inhibiting ferroptosis and alleviating IRI. Results Multiple omics analyses confirmed that SS-USCs possess strong tissue repair and antioxidant capabilities, while RS-USCs have the potential to differentiate towards specific directions such as the kidney, nervous system, and skeletal system, particularly showing great application potential in renal system reconstruction. Further experiments demonstrated in vivo and in vitro models confirming that SS-USCs and SS-USCs-Exo significantly inhibit ferroptosis and alleviate severe fatty liver IRI, whereas the effects of RS-USCs/RS-USCs-Exo are less pronounced. Analysis comparing the proteomic differences between SS-USCs-Exo and RS-USCs-Exo revealed that SS-USCs-Exo primarily inhibit ferroptosis and improve cellular viability by secreting exosomes containing Glutathione Peroxidase 4 (GPX4) protein. This highlights the most suitable cell subtype for treating severe fatty liver IRI. Conclusions SS-USCs possess strong tissue repair and antioxidant capabilities, primarily alleviating ferroptosis in the donor liver of fatty liver through the presence of GPX4 protein in their exosomes. This highlights SS-USCs as the most appropriate cell subtype for treating severe fatty liver IRI.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-025-04819-z
Objective To investigate the delivery efficiency of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-EXOs) via intratympanic injection into vestibular end organs, evaluate their protective effects against gentamicin-induced vestibular dysfunction and hearing loss on gentamicin-induced vestibular dysfunction and hearing loss, and explore their regulatory mechanisms on hair cell apoptosis and autophagy. Methods Exosome characteristics were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. PKH26 labeling was used to trace their distribution in the vestibule. SD rats were randomly divided into four groups: control group, gentamicin group (GEN group), gentamicin + exosome group (GEN + EXO group), and gentamicin + dexamethasone group (GEN + DEX group). On day 6 after administration, vestibular function was assessed via open-field test and beam balance test. On day 7, high-frequency hearing (32 kHz) was detected by auditory brainstem response (ABR). The quantity and structural changes of hair cells were analyzed by immunofluorescence staining and scanning electron microscopy. Proteomics was used to analyze differentially expressed proteins in vestibular tissues treated with dexamethasone or hucMSC-EXOs. The regulatory effects on Caspase-3 (apoptosis) and LC3 (autophagy) were validated by immunofluorescence. Results hucMSC-EXOs administered via intratympanic injection were found to target the utricle, saccule, and crista ampullaris. Behavioral studies showed that the GEN + EXO group exhibited significant suppression of gentamicin-induced reduction in total movement distance (p < 0.05) and movement speed (p < 0.05, superior to the GEN + DEX group), with a 60.5% reduction in beam balance test passage time (p < 0.05). ABR results revealed that the auditory threshold at 32 kHz in the GEN + EXO group was 18.3 dB SPL lower than that in the injury group (p < 0.01), with no statistical difference compared to the GEN + DEX group. Hair cell counting showed significant protective effects of exosomes in reducing hair cell loss in the utricular striola (+25%), saccular striola (+44%), and central crista ampullaris
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03745-w
Background Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. Methods The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. Results The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. Conclusions The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024086
Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024166
EGFR protein trafficking is critical for regulating multiple biological processes, including cell growth and survival. However, how EGFR protein homeostasis is maintained remains unclear. In this study, we show that a reduction in plasma membrane-associated EGFR triggers EGFR transcription by promoting pSTAT3 nuclear localization. Nucleus-localized pSTAT3 binds to the EGFR gene promoter to transactivate EGFR. Moreover, erlotinib, an EGFR tyrosine kinase inhibitor (TKI), can also increase pSTAT3 nuclear accumulation, resulting in increased EGFR transcription and erlotinib resistance. Importantly, pharmacological inhibition of pSTAT3 can significantly overcome the resistance of cancer cells to erlotinib. Together, these findings demonstrate that pSTAT3 is pivotal for maintaining EGFR protein homeostasis and suggest that activation of the pSTAT3-EGFR axis contributes to EGFR-TKI resistance.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024075
Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024227
Fibroblast growth factor 21 (FGF21) plays a pivotal role in regulating metabolic processes and energy homeostasis, making it a promising therapeutic avenue for various obesity-related conditions. However, its therapeutic efficacy faces challenges due to its suboptimal pharmacokinetics and bioactivity. To overcome these limitations, we adapt a strategy in which key amino acid residues responsible for enhanced activity are pinpointed through sequence alignment and comparative analysis to develop long-acting FGF21 analogs. The mutant FGF21 analogs are fused with the Fc fragment. Here, we report the design, identification, and characterization of two distinct Fc-fused FGF21 analogs, Fc-FGF21(P119R) and Fc-FGF21(H125R), with significantly augmented potency. These findings hold promise for clinical applications, offering potential interventions for obesity-related metabolic disorders.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024092
Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21344
BACKGROUND: Neural stem cells located in the ventricular zone and subventricular zone are crucial for cortical neurodevelopment and the treatment of neurodegenerative diseases. However, their precise regulatory mechanisms remain incompletely understood. miRNA-9 is one of the most abundantly expressed miRNAs in the vertebrate embryonic and adult brain, playing diverse roles during development. Nevertheless, the role of miR-9 in neural stem cell differentiation remains unclear. OBJECTIVE: To investigate the role of miR-9 in regulating the differentiation of neural stem cells in the ventricular zone and subventricular zone. METHODS: Neural stem cells were isolated from the ventricular zone and subventricular zone of embryonic day 14.5 ICR mice and cultured in proliferation medium for 3-4 days to form neurospheres. Stemness was identified by Pax6/Nestin immunofluorescence double staining. The expression profile of miR-9 was detected by qRT-PCR in telencephalon tissues at embryonic days 12.5, 14.5, 16.5, 18.5 and postnatal days 0, 7, as well as in embryonic day 14.5 neural stem cells cultured in vitro. Neural stem cells were transfected with miR-9 inhibitor or mimic using transfection reagents. After 24 hours, cells were differentiated for 3-4 days (neurons) and 6-8 days (glial cells). The differentiation of each lineage was quantified by immunofluorescence staining for Tuj1 (neuronal marker), myelin basic protein (oligodendrocyte marker), and glial fibrillary acidic protein (astrocyte marker). RESULTS AND CONCLUSION: qRT-PCR results showed that miR-9 was highly expressed in early embryonic telencephalon (E12.5-E14.5) and gradually decreased with development (E16.5 to P7). In E14.5 neural stem cells, miR-9 expression level was close to 90% of the internal reference RNU6B. Functional experiments showed that compared with the control group, the miR-9 inhibition group had decreased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, while the proportion of glial fibrillary acidic protein-positive astrocytes increased. Conversely, the miR-9 overexpression group had increased proportions of Tuj1-positive neurons and myelin basic protein-positive oligodendrocytes, and decreased proportion of glial fibrillary acidic protein-positive astrocytes, with significant differences (P < 0.001). These results indicate that miR-9 plays a bidirectional regulatory role in neural stem cell differentiation: (1) It participates in the temporal regulation of neurogenesis through developmental stage-specific expression patterns (high early, downregulated later); (2) It maintains the balance of trilineage differentiation by promoting neuronal and oligodendrocyte differentiation while inhibiting astrocyte generation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21419
BACKGROUND: Experiments have confirmed that ferroptosis is closely associated with a variety of orthopedic diseases. However, the specific mechanisms by which the regulation of ferroptosis leads to orthopedic diseases remain unclear. Current evidence suggests that signaling pathways may be an important approach for regulating the occurrence of ferroptosis. OBJECTIVE: To summarize the relevant signaling pathways involved in the regulation of ferroptosis in orthopedic diseases (osteoarthritis, spinal cord injury, osteoporosis, intervertebral disc degeneration, rheumatoid arthritis, osteosarcoma, steroid-induced osteonecrosis of the femoral head), to describe the key regulators of the ferroptosis pathway in orthopedic diseases through the modulation of the conduction of signaling pathways, and to conduct an in-depth study on the regulatory mechanisms of ferroptosis in orthopedic diseases and provide a theoretical basis for the prevention and treatment of such diseases. METHODS: Databases including PubMed, Elsevier, Web of Science, and CNKI were searched for relevant literatures on ferroptosis and related orthopedic diseases from the establishment of these databases up to February 2025. The search terms were "ferroptosis, osteoarthritis, osteoporosis, spinal cord injury, intervertebral disc degeneration, osteosarcomas, rheumatoid arthritis, steroid-induced osteonecrosis of the femoral head". A total of 138 articles were included for review. RESULTS AND CONCLUSION: (1) Under the regulation of multiple signaling pathways, the accumulation of intracellular iron ions, reactive oxygen species, and other substances can be induced, causing ferroptosis in osteoblasts, chondrocytes, osteosarcoma cells, etc., leading to changes in the microenvironment, thereby promoting or inhibiting the occurrence of related orthopedic diseases. (2) Studies have confirmed that signaling pathway-regulated ferroptosis is of great significance in the pathogenesis of orthopedic diseases. (3) However, the interaction mechanisms among signaling pathways, ferroptosis, and orthopedic diseases are still in the preliminary stage, and further research is needed to provide more strategies for the treatment of orthopedic diseases.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21482
BACKGROUND: During the repair process following tendon injury, an excessive inflammatory response can cause tendon cell apoptosis, thereby leading to a reduction in the biomechanical properties of the tendon. Meanwhile, a persistent inflammatory response can also trigger tissue fibrosis and adhesion. Studies have confirmed that interleukin-10 exerts an inflammatory regulatory role in connective tissue cells such as fibroblasts and can block inflammatory responses produced in various models. OBJECTIVE: To explore the effect of interleukin-10 against inflammatory responses following acute tendon injury. METHODS: Forty-two Sprague-Dawley rats were randomly divided into a normal group (n=6), model group (n=12), control group (n=12), and intervention group (n=12). Except for the normal group, the other three groups underwent acute Achilles tendon injury modeling via intra-tendinous injection of type I collagenase solution (the model was successfully established after 3 days). On the day of modeling, the control and intervention groups were subjected to daily injections of PBS and interleukin-10 protein solution, respectively, at the 1 cm points on both sides of the hind limb midline and abdominal midline intersection. Injections were given once daily for 4 consecutive days. On day 3 after successful modeling, ultrasound examination of the Achilles tendon was performed. On days 3 and 7 after successful modeling, tissue samples were collected for hematoxylin-eosin staining to observe pathological changes, immunohistochemical staining to detect phosphorylated nuclear factor kappa B (p-NF-κB) and tumor necrosis factor alpha (TNF-α) protein expression, RT-PCR to detect NF-κB, TNF-α, and cyclooxygenase-2 (COX-2) mRNA expression, and western blot to detect p-NF-κB, TNF-α, and COX-2 protein expression. RESULTS AND CONCLUSION: Ultrasound showed that the model group had blurred tendon boundaries and increased thickness, while the intervention group had clearer boundaries and thickness close to normal. Hematoxylin-eosin staining on day 3 showed that the model and control groups had disordered collagen fibers, massive inflammatory cell infiltration, and round nuclei concentrated; the intervention group had reduced fiber disorder, fewer inflammatory cells, and more elongated spindle-shaped tenocytes. On day 7, the model and control groups showed significantly improved collagen fiber arrangement, reduced inflammatory infiltration, and tenocytes transitioning from round to spindle shape with mostly aligned nuclei; the intervention group showed parallel and orderly collagen fibers approaching normal, further reduced inflammatory infiltration, and mostly elongated spindle-shaped tenocytes. Immunohistochemistry showed that on days 3 and 7, the model group had higher p-NF-κB and TNF-α protein expression than the normal and intervention groups (P < 0.05). RT-PCR showed that on days 3 and 7, the model group had higher NF-κB, TNF-α, and COX-2 mRNA expression than the normal and intervention groups (P < 0.05). Western blot showed that on days 3 and 7, the model group had higher p-NF-κB, TNF-α, and COX-2 protein expression than the normal group (P < 0.05); on day 3, the intervention group had lower p-NF-κB, TNF-α, and COX-2 protein expression than the model group (P < 0.05). These findings indicate that interleukin-10 can alleviate inflammatory responses during acute tendon injury repair.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21616
BACKGROUND: The complexity of hip joint anatomy makes it difficult to quantitatively assess by parameter indexes, and real-image rendering technology is important for the accurate display of hip joint microstructure and detection of diseases. OBJECTIVE: To evaluate the anatomical and morphological parameters of the hip joint through three-dimensional digital measurement by CT multi-planar reconstruction and cinematic rendering, compare the differences and analyze the correlation, so as to provide a precise anatomical parameter basis for the diagnosis and evaluation of hip-related diseases and hip replacement. METHODS: A total of 156 subjects (312 hips) aged ≥18 years without hip trauma or disease were included and divided into 6 groups by 10-year age intervals. CT images were processed with cinematic rendering and multi-planar reconstruction. Bilateral hip joint parameters including acetabular abduction angle, femoral head center distance, acetabular coverage, acetabular depth, neck-shaft angle, femoral offset, center-edge angle, acetabular anterior sector angle, acetabular posterior sector angle, and acetabular anteversion angle were measured. SPSS software was used to compare differences between different age groups and analyze correlations among anatomical parameters and with clinical baseline data. RESULTS AND CONCLUSION: (1) Significant differences were found between left and right sides for neck-shaft angle and femoral offset (P < 0.05). (2) By gender, acetabular abduction angle, femoral offset, and acetabular anteversion angle were greater in females than males (P < 0.05). (3) By age group, the young group had smaller acetabular maximum depth, acetabular coverage, acetabular anterior sector angle, acetabular posterior sector angle, and center-edge angle than the elderly group (P < 0.05). (4) No significant differences were found between traditional and innovative methods for acetabular coverage, and between coronal and axial positions for acetabular maximum depth, but significant correlations existed (r=0.76, 0.95, P < 0.01). Acetabular abduction angle was negatively correlated with body mass index, acetabular coverage, acetabular maximum depth, center-edge angle, acetabular anterior sector angle, and acetabular posterior sector angle (P < 0.05), and the latter five indicators were positively correlated with each other (P < 0.01). (5) Cinematic rendering and multi-planar reconstruction are beneficial for precise measurement and evaluation of hip joint anatomical parameters. There are significant differences in parameters among different genders and age groups, showing certain characteristic trends, and significant correlations exist among different anatomical parameters.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.