Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03886-y
Background Understanding the lineage differentiation of human prostate not only is crucial for basic research on human developmental biology but also significantly contributes to the management of prostate-related disorders. Current knowledge mainly relies on studies on rodent models, lacking human-derived alternatives despite clinical samples may provide a snapshot at certain stage. Human embryonic stem cells can generate all the embryonic lineages including the prostate, and indeed a few studies demonstrate such possibility based on co-culture or co-transplantation with urogenital mesenchyme into mouse renal capsule. Methods To establish a stepwise protocol to obtain prostatic organoids in vitro from human embryonic stem cells, we apply chemicals and growth factors by mimicking the regulation network of transcription factors and signal transduction pathways, and construct cell lines carrying an inducible NKX3-1 expressing cassette, together with three-dimensional culture system. Unpaired t test was applied for statistical analyses. Results We first successfully generate the definitive endoderm, hindgut, and urogenital sinus cells. The embryonic stem cell-derived urogenital sinus cells express prostatic key transcription factors AR and FOXA1, but fail to express NKX3-1. Therefore, we construct NKX3-1-inducible cell line by homologous recombination, which is eventually able to yield AR, FOXA1, and NKX3-1 triple-positive urogenital prostatic lineage cells through stepwise differentiation. Finally, combined with 3D culture we successfully derive prostate-like organoids with certain structures and prostatic cell populations. Conclusions This study reveals the crucial role of NKX3-1 in prostatic differentiation and offers the inducible NKX3-1 cell line, as well as provides a stepwise differentiation protocol to generate human prostate-like organoids, which should facilitate the studies on prostate development and disease pathogenesis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a complex pathogenesis that was previously thought to involve primarily adaptive immunity. Emerging evidence underscores the role of neutrophils in shaping immune dysregulation and inducing organ damage in lupus. This study aims to investigate the dynamics of neutrophil senescence and its relationship with lupus, an area that remains poorly understood. Here, we identify a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in the peripheral blood of SLE patients compare to that in the healthy donors. Increased numbers of senescence-like neutrophils are positively correlated with SLE disease activity and autoantibody production in SLE patients. In addition, senescence-like neutrophils derived from SLE patients exhibit an impaired ability to suppress the proinflammatory activity of natural killer (NK) cells and CD4+ T cells. Further mechanistic exploration suggests that these senescence-like neutrophils might exert their immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results demonstrate that senescence-like neutrophils could serve as biomarkers for assessing the disease activity of SLE. The compromised immunosuppressive function of senescence-like neutrophils provides a new perspective on SLE pathophysiology and may pave the way for the development of novel therapies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025183
Hepatocyte phospholipase D1 (PLD1) knockout alleviates metabolic dysfunction-associated steatotic liver disease (MASLD) in mice, but the underlying mechanism is largely unknown. In this study, the mice are divided into four groups: Con (wild-type mice with normal control diet), HFHC (wild-type mice with high-fat diet), Con_KO (hepatocyte PLD1-knockout mice with normal control diet), and HFHC_KO (hepatocyte PLD1-knockout mice with high-fat diet). Intestinal contents of mice are analyzed via metagenomics and metabolomics, and the liver bile acids are assessed by mass spectrometry imaging. The results show that at the phylum level the abundance of Bacillota in the intestines of MASLD model mice is significantly increased, whereas that of Bacteroidota significantly is decreased. However, after the deletion of hepatocyte PLD1, Pseudomonadota and Candidatus Bathyarchaeota are significantly decreased in the MASLD model mice. At the species level, compared with that in the Con group, the abundance of Faecalibaculum rodentium is significantly increased in the HFHC group, whereas hepatocyte PLD1 knockout causes the abundances of Desulfovibrionaceae bacterium LT0009 and Lachnospiraceae bacterium 10-1 to be significantly decreased. In terms of intestinal bile acids, the levels of two bile acids (hyodeoxycholic acid and glycolithocholic acid) differ between the HFHC_KO group and the HFHC group. Association analysis shows that Faecalibaculum co-occurs with DCA, βMCA, ΩMCA and αMCA, while probiotic Bacteroides uniformis is significantly correlated with UDCA, 12-KetoLCA, and 7-KetoLCA. Finally, mass spectrometry imaging reveals that the TCA and TDCA contents in the liver are significantly decreased after PLD1 knockout in hepatocytes. These findings demonstrate that hepatocyte PLD1 knockout alters the gut microbiota and bile acids profiles, suggesting that PLD1 deficiency may modulate MASLD progression by changing intestinal microbiota-bile acid homeostasis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026104
Reperfusion therapy is critical for acute myocardial infarction but is often accompanied by myocardial ischemia/reperfusion injury (MIRI). Phillyrin, a natural lignan from Forsythia suspensa, exerts anti-inflammatory and antioxidant effects; however, its role and mechanism in MIRI remain unclear. In this study, HL-1 cardiomyocytes are subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Cell viability, apoptosis, oxidative stress, and inflammation are measured after phillyrin treatment. Multiomics (mRNA-seq, proteomics, and acetylproteomics) is used to identify key targets and pathways. Molecular docking, co-immunoprecipitation, site-directed mutagenesis, and western blot analysis are used to validate posttranslational regulation. A mouse MIRI model is established to confirm the in vivo cardioprotective effects of phillyrin. Phillyrin preserves cell viability and reduces apoptosis, oxidative stress, and inflammation in OGD/R-injured HL-1 cells. Multiomics integration reveals that phillyrin acts primarily through posttranslational regulation and highlights kinetochore scaffold 1 (KNL1) as the only protein that is both upregulated and hyperacetylated at lysine 605 (K605). Mechanistically, phillyrin may bind to the KNL1 C-terminus and enhance the interaction between KNL1 and acetyltransferase p300/CBP. KNL1 K605R mutation and Knl1 knockdown reduce KNL1 protein expression and reverse the inhibitory effects of phillyrin on p53 pathway-mediated apoptosis, oxidative stress, and inflammation. In mouse MIRI models, phillyrin reduces infarct size, myocardial damage, and cardiomyocyte apoptosis; these effects are abolished by knockdown of Knl1. Therefore, phillyrin promotes KNL1 acetylation at K605 to increase KNL1 protein expression, thereby inhibiting p53 signaling and alleviating apoptosis, oxidative stress, and inflammation in MIRI. This study identifies KNL1 acetylation at K605 as a novel posttranslational modification target for cardioprotection.
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•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•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•2026•DOI: 10.3724/abbs.2025223
The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026104
Reperfusion therapy is critical for acute myocardial infarction but is often accompanied by myocardial ischemia/reperfusion injury (MIRI). Phillyrin, a natural lignan from Forsythia suspensa, exerts anti-inflammatory and antioxidant effects; however, its role and mechanism in MIRI remain unclear. In this study, HL-1 cardiomyocytes are subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Cell viability, apoptosis, oxidative stress, and inflammation are measured after phillyrin treatment. Multiomics (mRNA-seq, proteomics, and acetylproteomics) is used to identify key targets and pathways. Molecular docking, co-immunoprecipitation, site-directed mutagenesis, and western blot analysis are used to validate posttranslational regulation. A mouse MIRI model is established to confirm the in vivo cardioprotective effects of phillyrin. Phillyrin preserves cell viability and reduces apoptosis, oxidative stress, and inflammation in OGD/R-injured HL-1 cells. Multiomics integration reveals that phillyrin acts primarily through posttranslational regulation and highlights kinetochore scaffold 1 (KNL1) as the only protein that is both upregulated and hyperacetylated at lysine 605 (K605). Mechanistically, phillyrin may bind to the KNL1 C-terminus and enhance the interaction between KNL1 and acetyltransferase p300/CBP. KNL1 K605R mutation and Knl1 knockdown reduce KNL1 protein expression and reverse the inhibitory effects of phillyrin on p53 pathway-mediated apoptosis, oxidative stress, and inflammation. In mouse MIRI models, phillyrin reduces infarct size, myocardial damage, and cardiomyocyte apoptosis; these effects are abolished by knockdown of Knl1. Therefore, phillyrin promotes KNL1 acetylation at K605 to increase KNL1 protein expression, thereby inhibiting p53 signaling and alleviating apoptosis, oxidative stress, and inflammation in MIRI. This study identifies KNL1 acetylation at K605 as a novel posttranslational modification target for cardioprotection.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21241
BACKGROUND: Ferroptosis plays a critical role in doxorubicin-induced cardiomyopathy; however, its specific regulatory mechanisms require further elucidation. Piwi-interacting RNA 413 (piRNA413) regulates ferroptosis in doxorubicin-induced cardiomyocytes, designated as cardiac ferroptosis-associated piRNA (CFAPIR). However, the specific regulatory mechanism needs to be further elucidated. OBJECTIVE: To investigate the role and regulatory mechanism of piRNA CFAPIR in doxorubicin-induced cardiomyocyte ferroptosis and cardiomyopathy. METHODS: (1) Intraperitoneal injection of doxorubicin was used to induce cardiomyopathy in mice. The myocardium was in situ injected with CFAPIR knocking down lentivirus. The body mass and survival rate of mice were monitored and recorded; cardiac function, heart volume and mass, inflammation, and cardiac fibrosis were assessed. (2) Doxorubicin was used to induce ferroptosis in AC16 cardiomyocytes, and CFAPIR inhibitor was transfected into cells. Cell damage, ferroptosis (expression levels of ferroptosis markers, iron ion, malondialdehyde, and reduced glutathione content), and mitochondrial dysfunction were detected. The effect of CFAPIR on ABCB8 expression was also examined. RESULTS AND CONCLUSION: (1) CFAPIR levels were significantly upregulated in both doxorubicin-induced cardiomyopathy animal models (P < 0.0001) and cardiomyocyte ferroptosis models (P < 0.01). (2) In vivo, knockdown of CFAPIR significantly alleviated doxorubicin-induced cardiotoxicity, including inhibition of body weight loss (P < 0.05), improved survival rate, improved cardiac function (P < 0.01), reduced cardiac atrophy (P < 0.05), inhibited lactate dehydrogenase activity increase (P < 0.05), and reduced cardiac fibrosis (P < 0.0001). (3) In vitro, knockdown of CFAPIR significantly ameliorated doxorubicin-induced cardiomyocyte ferroptosis, manifested by increased cell viability (P < 0.05), decreased lactate dehydrogenase activity (P < 0.01), upregulated expression of ferroptosis markers xCT (P < 0.01) and glutathione peroxidase 4 (P < 0.001), downregulated mRNA level of prostaglandin-endoperoxide synthase 2 (P < 0.05), reduced iron overload (P < 0.05), decreased malondialdehyde content (P < 0.05), increased reduced glutathione content (P < 0.01), reduced reactive oxygen species accumulation (P < 0.01), and increased mitochondrial membrane potential (P < 0.05). (4) Knockdown of CFAPIR significantly attenuated the doxorubicin-induced decrease in iron transporter ABCB8 expression (P < 0.05). (5) These results indicate that CFAPIR levels are significantly upregulated in both animal models of doxorubicin-induced cardiomyopathy and cellular ferroptosis models, and knockdown of CFAPIR significantly improves doxorubicin-induced cardiotoxicity and cardiomyocyte ferroptosis, possibly by targeting mitochondrial iron transporter ABCB8.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21462
BACKGROUND: In recent years, bioceramic materials have become the preferred materials for retrograde apical filling due to their excellent biocompatibility and sealing properties. The bioceramic materials C-Root BP and iRoot BP Plus both exhibit excellent biocompatibility and sealing properties. OBJECTIVE: To compare the apical sealing performance and resistance strength of C-Root BP and iRoot BP Plus materials in vitro. METHODS: From June 2022 to June 2024, 56 freshly extracted single detached teeth at the Department of Stomatology, Shijiazhuang Second Hospital due to orthodontics or periodontal disease were collected and randomly divided into four groups. The iRoot BP Plus group (n=16) and C-Root BP group (n=16) were respectively treated with iRoot BP Plus and C-Root BP materials for root tip filling. The positive control group (n=16) was treated with distilled water for root tip filling, while the negative control group (n=8) was not treated with root tip filling and only underwent routine root canal preparation and disinfection. Dye penetration method was used to detect apical sealing; bacterial microleakage was evaluated using an in vitro model; push-out test was used to measure the bond strength between filling material and dentin, and fracture patterns were observed under microscope. RESULTS AND CONCLUSION: After 7 days of dye staining, the dye penetration length in the positive control group was greater than that in the iRoot BP Plus and C-Root BP groups (P < 0.05), with no significant difference between the iRoot BP Plus and C-Root BP groups (P > 0.05). After 90 days of culture, the incidence of bacterial microleakage in the positive control group was higher than that in the iRoot BP Plus and C-Root BP groups (P < 0.05), with no significant difference between the iRoot BP Plus and C-Root BP groups (P > 0.05). The bond strength between filling material and dentin in the C-Root BP group was greater than that in the iRoot BP Plus group (P < 0.05), and there was no significant difference in fracture patterns between the two groups (P > 0.05). These results indicate that C-Root BP and iRoot BP Plus materials can produce similar apical sealing effects and fracture patterns, but C-Root BP material has better bond strength.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21449
BACKGROUND: Percutaneous coronary intervention stent implantation is primarily used to treat coronary artery stenosis. However, current multi-objective stent optimization methods are limited by sample size constraints, resulting in insufficient prediction accuracy when balancing key performance indicators such as support and compliance, hindering the effectiveness of stent optimization design. OBJECTIVE: To establish an innovative optimization framework for coronary stents based on a ensemble surrogate model. METHODS: A three-dimensional parametric model of the vascular stent was constructed, and a mechanical response database was established through finite element simulation. A dynamic weight fusion strategy was adopted to integrate the global optimization characteristics of the Kriging model and the local nonlinear representation advantages of the radial basis function model. A ensemble surrogate model was constructed based on 20 groups of initial samples, and the non-dominated sorting genetic algorithm-II was used to optimize the parameter space. RESULTS AND CONCLUSION: Experimental results demonstrated that the ensemble surrogate model exhibited significant advantages in the finite sample setting. The coefficient of determination for the inverse prediction of the radial stiffness of the stent reached 0.974 2, a 4.4% improvement compared to the single model, validating the efficient modeling capability of the ensemble surrogate model in the finite sample setting. The prediction accuracy of the stent's bending stiffness also improved by 4.4% compared to the single radial basis function surrogate model. After optimization, the stent performance achieved dual-objective synergistic optimization. The inverse radial stiffness of the stent in the ensemble surrogate model group was reduced by 13.92% and 9.57% compared to the Kriging model group and the single radial basis function surrogate model group, respectively. The bending stiffness of the stent was optimized by 0.38% and 2.56% compared to the Kriging model group and the single radial basis function surrogate model group, respectively. The proposed ensemble surrogate model breaks through the performance limitations of traditional single models, providing a low-cost, high-precision solution for the 'rigid-flexible' synergistic optimization of coronary stents.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21486
BACKGROUND: Studies have shown that tissue clearing technology enables the three-dimensional (3D) visualization of neurons in the spinal cord injury area, clearly presenting morphological changes of neurons, including soma atrophy, dendrite fragmentation, and axonal degeneration. OBJECTIVE: To systematically evaluate the application potential of tissue clearing technology in a rat model of chronic spinal cord injury. METHODS: Thirty-six female Sprague-Dawley rats were randomly and equally divided into a normal group (n=12), a sham surgery group (n=12), and a surgery group (n=12). The normal group received no treatment. The sham group underwent implantation and immediate removal of a poly(vinyl alcohol)/polyacrylamide interpenetrating network hydrogel into the C5-C7 spinal canal. The surgery group received implantation of the hydrogel to compress the spinal cord at C5-C7 to establish a chronic spinal cord injury model. At postoperative days 1, 3, 7, and 14, motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) score and the modified Rivlin inclined plane test. At day 14, spinal cord tissue was harvested for hematoxylin-eosin staining to observe morphology, and tissue clearing combined with neuron-specific nuclear protein immunofluorescence labeling was used for three-dimensional reconstruction and cross-sectional view analysis. RESULTS AND CONCLUSION: (1) The BBB scores and inclined plane test angles in the surgery group were significantly lower than those in the normal and sham groups at all time points (P < 0.001). (2) Hematoxylin-eosin staining showed significant spinal cord injury in the surgery group, with swelling and destruction of nerve cells in the gray matter, loss of uniformity in white matter structure, disappearance of some nuclei, reduced cell number, massive glial cell proliferation and aggregation in the compression area, disordered white matter structure, and formation of numerous cavities. (3) Three-dimensional reconstruction and cross-sectional analysis of the spinal cord showed that in the normal and sham groups, the spinal cord appeared continuous and full, with uniform distribution of neuron-specific nuclear protein red fluorescence, dense layered arrangement of neurons in the anterior horn of the gray matter, and intact white matter fiber tracts. In the surgery group, the spinal cord appeared depressed or even interrupted, with significantly reduced fluorescence intensity of neuron-specific nuclear protein in the compressed segment, disrupted gray matter neuronal layer structure, and regional fluorescence interruption. These results indicate that tissue clearing technology can effectively display structural changes after spinal cord injury, providing strong support for studying the pathological mechanisms of spinal cord injury.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026005
Chronic hyperglycemia-driven protein glycation in diabetes is a key pathogenic factor in vascular endothelial injury. This study demonstrates the multifaceted protective profile of aminoguanidine (AMG) against diabetes-induced vascular injury. As a carbonyl scavenger, AMG effectively traps methylglyoxal (MGO), inhibiting advanced glycation end products (AGEs) formation while preserving endothelial glycocalyx integrity and permeability. Mechanistically, AMG suppresses NF-κB-mediated inflammation, upregulates the eNOS/NO pathway, and restores CD31 expression, collectively mitigating oxidative stress, apoptosis and impaired proliferation in human umbilical vein endothelial cells (HUVECs). Metabolomic profiling further reveals AMG's capacity to alleviate MGO-induced metabolic dysregulation by modulating critical pathways, including glutathione metabolism and the TCA cycle. In diabetic mice, AMG attenuates site-specific glycation adducts on plasma albumin and demonstrates significant therapeutic efficacy by improving endothelial-dependent vasodilation via the eNOS/NO pathway, reducing vascular fibrosis and basement membrane thickening, and suppressing NF-κB-driven inflammatory responses. These integrated findings establish AMG as a promising therapeutic candidate with multifaceted protective effects against diabetic vascular injury.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025047
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex pathogenesis historically attributed to adaptive immunity. Emerging data implicate neutrophils in immune dysregulation and organ damage. This study investigates neutrophil senescence dynamics in SLE. We identified a significantly elevated proportion of CXCR4hiCD62Llo senescence-like neutrophils in peripheral blood of SLE patients versus healthy donors. Increased senescence-like neutrophil numbers positively correlated with SLE disease activity and autoantibody production. Functionally, senescence-like neutrophils from SLE patients exhibited impaired suppression of proinflammatory activity in natural killer (NK) cells and CD4+ T cells. Mechanistically, these cells may exert immunosuppressive effects via reactive oxygen species (ROS) production under physiological conditions. Our results position senescence-like neutrophils as candidate biomarkers for SLE disease activity. The compromised immunosuppressive function of these cells offers a new perspective on SLE pathophysiology and may inform development of novel therapies. Limitations include small sample size and heterogeneous treatment backgrounds, necessitating further validation. Future studies will address NET release and potential subset markers.