Genomics, Proteomics & Bioinformatics•2024•DOI: 10.1093/gpbjnl/qzad002
The order Acipenseriformes, which includes sturgeons and paddlefishes, represents “living fossils” with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04806-4
Background The human umbilical cord (hUC)–mesenchymal stem cell (MSC) secretome (SCT) is a cell-free therapy that may emerge as a novel therapeutic strategy for hair loss prevention. Here, we aimed to elucidate the underlying mechanisms through which SCT regulates hair growth and cycle transition. Methods Using C57BL/6 mice, ex vivo follicles, and cell experiments, we studied the effects and mechanisms of SCT on hair growth and cycling using untargeted metabolomics and phosphoproteomics. A three-month double-blind clinical study was conducted to validate the effects of SCT on human hair. Results SCT promotes the telogen-to-anagen transition, hair thickening, and elongation of the vibrissae in mice; regulates dermal papilla cells and hair matrix cells through cysteine and methionine metabolism; and stimulates methylthioadenosine synthesis in hair matrix cells by activating the PI3K/AKT/mTOR signaling pathway. Clinical studies demonstrated that SCT increased human hair density and average hair diameter. Scalp physiological tests and subjective feedback indicated no related adverse reactions on the scalp or hair. Conclusions SCT promoted hair growth, thickening, and the hair follicle cycle via the PI3K/AKT/mTOR signaling pathway. This research provides a basis for the application of cell-free alternatives in hair care and hair loss prevention.
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.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04274-w
Background Alternative splicing not only expands the genetic encoding of genes but also determines cellular activities. This study aimed to elucidate the regulation mechanism and biological functions of lincRNA-ASAO in the process of odontogenesis-related genes alternative splicing mediated odontogenic differentiation of hDPSCs. Methods RACE, RNA-seq, FISH and bioinformatics techniques were used to identify novel lincRNA-ASAO. ALP staining, alizarin red staining, qRT-PCR and western blot were used to identify the role of lincRNA-ASAO in regulating the odontoblast differentiation of hDPSCs. The binding protein PTBP1 of lincRNA-ASAO was screened by RNA-Pull-down, protein profiling and bioinformatics. The target gene ALPL of lincRNA-ASAO/PTBP1 was identified by RNA-seq, bioinformatics technology and DNA agarose gel electrophoresis. FISH, IF, PAR-CLIP and bioinformatics techniques were used to determine the roles of lincRNA-ASAO, PTBP1 and ALPL pre-mRNA in the odontoblast differentiation of hDPSCs. Results We identified a novel lincRNA-ASAO that could promote the odontogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). And, the interaction between lincRNA-ASAO and alternative splicing factor PTBP1 promoted the odontoblast differentiation of hDPSCs. In addition, lincRNA-ASAO forms duplexes with ALPL pre-mRNA, targeting PTBP1 to exonic splicing silencer (ESS) of ALPL and regulating exon 2 skipping. Notably, lincRNA-ASAO/PTBP1 regulated ALPL production to increase the type 2 splice variant, which promoted the odontoblast differentiation of hDPSCs. Conclusions We have identified the novel lincRNA-ASAO, which can promote the odontoblast differentiation of hDPSCs. The mechanism study found that lincRNA-ASAO/PTBP1 mediated the exon 2 skipping of ALPL pre-mRNA, resulting in the type 2 splice variant of ALPL. Our results enrich the understanding of lncRNAs and alternative splicing in regulating the odontoblast differentiation of hDPSCs, and provide clues to improve the clinical therapeutic potential of hDPSCs for dental pulp restoration.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025145
Angiopoietin-like 4 (ANGPTL4) expression is increased in wound tissue and contributes to wound healing. However, the underlying mechanisms are not fully understood. Here, we demonstrate that ANGPTL4 expression is significantly increased in epidermal stem cells (EpSCs) in the periwound epidermis during wound healing in mice. Increased Angptl4 expression is positively correlated with increased expressions of tumor growth factor-α, interleukin-1β, epidermal growth factor, nerve growth factor, fibroblast growth factor 7, and transforming growth factor-β1. Each of these molecules induces Angptl4 expression in mouse EpSCs. RNA sequencing of EpSCs derived from wild-type and Angptl4 knockout (Angptl4–/–) mice reveals altered expressions of genes involved in the cell cycle and cell proliferation in Angptl4–/– EpSCs, including a decrease in cyclin E2/A2/B1 and cyclin-dependent kinase 1 (Cdk1) expression; an increase in Cdk inhibitor 2a (Cdkn2a) and Cdkn2b expression; and a decrease in the prolactin (PRL) family members Prl2a1, Prl8a1, Prl8a9, and Prl8a6. Mechanistic studies reveal that ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated upregulation of cyclins A2/E2/B1 and Cdk1, downregulation of Cdkn2a, and acceleration of cell cycle progression from the G1 to the S and G2 phases. In vivo studies demonstrate that Prl8a6 mRNA is upregulated by ANGPTL4 in mouse periwound tissue during skin wound healing. Knockdown of Angptl4 or Prl8a6 in periwound skin tissue impairs EpSC proliferation and delays wound re-epithelialization. In conclusion, our study demonstrates that, after skin injury, elevated levels of proinflammatory cytokines and growth factors in periwound tissue stimulate Angptl4 expression in EpSCs and that ANGPTL4 promotes EpSC proliferation by increasing Prl8a6 expression, thereby accelerating wound re-epithelialization.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025170
Cryptococcus gattii causes cryptococcosis and life-threatening cryptococcal meningitis. Currently, the pathogenic virulence mechanisms of C. gattii remain a significant area of ongoing research with considerable unexplored aspects. On the basis of our established research, a sub-cluster of strains with independent evolutionary relationships from WM276 in the phylogenetic analysis of VGI-type strains is identified. In vivo infection experiments on this sub-branch of strains reveal that there are hypervirulent strains and hypovirulent strains among these strains, and the virulence differences are significant (P < 0.001). Bioinformatic interrogation of differentially expressed genes reveals that the catalase-encoding gene CGB_J0620W, CAT2, is a pivotal virulence-associated gene. The hypervirulent clinical isolate G4 (G4-WT) is selected as the parental strain, from which an isogenic CAT2-knockout mutant (cat2Δ) is constructed via homologous recombination, which shows increased sensitivity to oxidative stress, as well as growth defects in response to hyperosmosis, 5-fluorocytosine, fluconazole and amphotericin B. The cat2Δ::CAT2 strain exhibits phenotypic restoration to wild type (WT). In the mouse experiments, significant differences in survival (P < 0.001), pulmonary fungal burden (P < 0.01), and alveolar structural damage are observed between the WT and cat2Δ strains, which are completely different from C. neoformans. Moreover, comparative transcriptome analysis is performed on the WT and cat2Δ strains, which reveals that enzymes encoded by CAT2 may be involved in oxidative stress, metabolism and sugar transport. In conclusion, this study may explain the differences in virulence among different genetic evolutionary processes of a sub-cluster of the VGI geneotype of C. gattii and provide a theoretical basis for targeted therapy in a specific genotype population in the future.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025112
Ferroptosis is a lytic form of regulated cell death that is driven by iron-dependent lipid peroxidation and has been implicated in various diseases, including acute kidney injury (AKI). Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and possesses various pharmacological activities, including anti-inflammatory and antioxidative properties. However, it is unclear whether scutellarin can inhibit ferroptosis and mitigate related diseases. In this study, we show that scutellarin can inhibit ferroptosis in both human HK-2 cells and mouse bone marrow-derived macrophages stimulated with RSL3 or erastin. Mitochondrial dysfunction and reactive oxygen species generation are counteracted by scutellarin treatment, suggesting the involvement of its antioxidative activity. Furthermore, scutellarin increases the nuclear levels of Nrf2 and the expressions of its target genes, including HO-1 and GPX4. Scutellarin-mediated inhibition of ferroptosis and increases in these proteins are abrogated by co-treatment with brusatol, an Nrf2 inhibitor, indicating an essential role for Nrf2 in this process. In a mouse model of folic acid-induced AKI, scutellarin mitigates acute renal damage, as revealed by histopathological analysis and serum blood urea nitrogen and creatinine assays. Folic acid-induced acute renal injury is associated with increased ferroptosis, as revealed by elevated level of 4-hydroxynonenal (4-HNE), a surrogate marker of ferroptosis, which is diminished by scutellarin co-treatment. Specifically, the elevated 4-HNE levels in macrophages (MAC-2 positive) and other renal cells are suppressed by scutellarin. Overall, scutellarin can inhibit ferroptosis both in cultured cells and in a mouse model of AKI by regulating Nrf2 signaling.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025146
Actin-bundling protein Fascin1 (FSCN1) is encoded by the Fscn1 gene and is crucial for cytoskeletal remodeling and cellular migration. Although a previous study linked Fscn1 deficiency to neonatal lethality in mice, the underlying metabolic mechanism remains unclear. In this study, we report that systemic knockout (KO) of Fscn1 leads to 52.2% mortality within 24 h post-birth, accompanied by severe hypoglycemia in KO pups compared with their littermates. Remarkably, this lethality is fully rescued by oral glucose administration, indicating a glucose supply-dependent survival mechanism. Surviving Fscn1-KO neonates display persistent developmental deficits, including growth retardation and depleted lipid stores, despite intact canonical insulin-regulated hepatic gluconeogenic pathways. Transcriptomic profiling of P0 livers reveals that Fscn1 loss predominantly disrupts metabolic pathways, with the glycerol phosphate shuttle being the most significantly downregulated module. Mechanistically, Fscn1-KO livers exhibit markedly reduced protein levels of glycerol-3-phosphate dehydrogenase isoforms (GPD1/GPD2), key enzymes bridging glycolysis and gluconeogenesis. Consistently, glycerol tolerance tests demonstrate impaired glycerol-to-glucose conversion in Fscn1-KO mice, confirming defective glycerol-driven gluconeogenesis. Our findings establish FSCN1 as a novel cytoskeletal-metabolic integrator essential for neonatal survival by sustaining hepatic glucose production from glycerol, thus revealing an unexpected role of actin dynamics in coordinating metabolic adaptation during early postnatal development.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024149
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and poses a substantial health burden with increasing incidence globally. NAFLD encompasses a spectrum extending from hepatic steatosis to nonalcoholic steatohepatitis (NASH), with the possibility of progressing to cirrhosis or, in severe instances, hepatocellular carcinoma (HCC). NAFLD extends beyond simple metabolic disruption and involves multiple immune cell-mediated inflammatory processes. Integrins are a family of heterodimeric transmembrane cell adhesion receptors that regulate various aspects of NAFLD onset and progression, including hepatocellular steatosis, hepatic stellate cell (HSC) activation and immune cell infiltration. In this review, we comprehensively summarize the involvement of integrins in NAFLD, as well as the downstream signal transduction mediated by these receptors. Furthermore, we present the latest clinical and preclinical findings on drugs that target integrins for steatosis, inflammation, fibrosis and NAFLD-related HCC treatment.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024114
With the increasing global population and aging demographic, the incidence of stroke is rising. Among these, ischemic stroke (IS), also known as cerebral ischemia, constitutes over 80% of all stroke cases. This condition is characterized by an acute cerebrovascular disease caused by the blockage and interruption of the brain's blood supply, resulting in localized tissue ischemia, oxygen, and glucose deficiency, ultimately leading to the death of nerve cells and tissue necrosis [1,2]. "Vascular recanalization and the restoration of cerebral blood flow" are the primary clinical treatment objectives and are achieved through the intravenous administration of drugs such as tissue plasminogen activator or through surgical thrombectomy. These interventions not only restore the delivery of oxygen and glucose to the affected cerebral area but also help prevent the expansion of the infarcted region. However, the restoration of reperfusion cerebral blood flow similarly exposes the infarct area to peripheral immune cells, triggering the activation of the immune response and inflammation-induced injury [3]. Research indicates that IS elicits a robust inflammatory response, with neuroinflammation playing a crucial role in the secondary neurodegeneration process following stroke. Neuroinflammatory responses are initiated and perpetuated through injury cascades that include the release of inflammatory mediators, the migration and recruitment of white blood cells across the blood-brain barrier, and the impairment of endothelial nitric oxide synthase. These mechanisms collectively promote the activation of pro-inflammatory genes, which in turn activate microglia (MG) and exacerbate ischemic damage and neurological dysfunction [4]. MG are resident immune cells of the central nervous system (CNS). Its function is akin to that of macrophages, serving as the first line of defense against injuries within the central nervous system. Under typical conditions, brain microglia participate in immune surveillance and defense against infectious agents. However, in the pathogenesis of neurodegenerative diseases such as IS, MG are activated by various stimuli. Once activated, MG are known to release numerous proinflammatory or cytotoxic factors, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS). These factors initiate the neuroinflammatory response, exacerbate inflammation, intensify damage to brain tissue and neurons, and significantly hinder the repair of brain injuries and neurogenesis [5,6]. Therefore, inhibiting the activation of microglia and reducing the inflammatory response in the central nervous system are crucial for minimizing brain damage caused by IS and are vital for developing effective prevention and treatment strategies. In recent years, certain natural compounds extracted from traditional drug formulations have shown high therapeutic potential in protecting the brain from cerebral ischemic injury. These compounds reduce the neuroinflammatory response and apoptosis following stroke. Traditional Chinese herbal medicine (TCHM) and its constituent herbs feature a multiplicity of components, targets, and pathways owing to their complex formulations and therapeutic principles, making them promising sources for developing effective treatments for IS. Panax notoginseng saponin (PNS), as the principal bioactive component of Panax notoginseng, is extensively utilized in the prevention and treatment of cardiovascular and cerebrovascular diseases. Its pharmacological benefits include dissipating blood stasis, promoting hemostasis, alleviating swelling and pain, regulating energy metabolism disorders, balancing ion metabolism, and reducing and accelerating the clearance of free radicals [7]. Research indicates that PNS mitigates apoptosis by maintaining mitochondrial homeostasis, enhancing the integrity of the blood‒brain barrier (BBB), augmenting cerebral blood supply, and fostering the differentiation of neural stem cells and proliferation of hippocampal neurons. In addition, PNS offers neuroprotection against focal cerebral I/R injury in rats by reducing brain edema, upregulating the expression of the heat shock protein HSP70, and downregulating the expression of transferrin [8,9]. Additionally, PNS has been reported to enhance the recovery of neurogenesis and neurological function in cerebral embolism induced by microspheres and to reduce sepsis-induced acute kidney injury by suppressing inflammation [10]. However, the mechanism by which PNS targets IS has not been fully elucidated. In this study, we investigated the anti-inflammatory effects of PNS on IS and identified potential target pathways that could inhibit microglia-mediated inflammatory response.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024192
Clitoria ternatea L. flowers are used as traditional herbal medicines and are known for their advanced pharmacological activities. Flavonoids and anthocyanins reportedly contribute to the therapeutic properties of C. ternatea flowers; however, their potential anti-bladder cancer effects and molecular mechanisms remain unknown. In this study, flavonoid- and anthocyanin-rich samples from C. ternatea flowers (DDH) are prepared via macroporous resin-based extraction coupled with an efficient and reliable two-dimensional UPLC-DAD-MS/MS method. In vitro and in vivo studies reveal that DDH can inhibit bladder cancer cell growth and enhance the anti-bladder cancer activity of cisplatin. RNA-seq combined with KEGG analysis reveals that fatty acid synthesis is closely related to the anti-bladder cancer effect of DDH. Furthermore, DDH dose-dependently reduces cellular fatty acid levels in bladder cancer cells, and the addition of fatty acids significantly mitigates DDH-induced cell growth inhibition. Subsequent findings reveal that DDH downregulates sterol regulatory element-binding protein 1 (SREBP1), a key transcriptional regulator of de novo fatty acid synthesis in cancer cells, and its downstream targets (FASN, SCD1, and ACC). Additionally, this study demonstrates that gallic acid not only enhances the stability of DDH but also synergistically potentiates its anti-bladder cancer activity. Our study suggests that targeting the SREBP1 pathway is an effective strategy in bladder cancer therapy, and the ability of DDH to induce cell death by inhibiting the SREBP1 pathway and its good tolerance in mice make it a promising strategy for preventing and treating bladder cancer.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024179
The ubiquitin-proteasome pathway is a highly selective protein degradation pathway that is capable of efficiently degrading intracellular proteins and plays an important role in various life processes. Dysfunction of this pathway has been associated with numerous problems, including cancer and neurodegenerative diseases. Targeted protein degradation (TPD) technologies have emerged as promising tools for use in a number of different areas, including biological research and clinical interventions. Recently, a technology named Trim-Away was developed for the rapid degradation of proteins in mammalian cells. Briefly, an antibody is designed against a target protein, and the E3 ligase TRIM21 is used to recognize the Fc region of the antibody and subsequently mediate antibody-dependent protein degradation via the proteasome. To enhance the protein degradation efficiency of Trim-Away, three TRIM21-based constructs were designed: (1) deletion of the B-box domain of TRIM21, termed TRIM21 (ΔBB), (2) substitution of the RING domain of TRIM21 with the RING domain of MKRN1, termed TRIM21-RING, and (3) substitution of the RING domain of TRIM21 with the HECT domain of UBE3A, designated TRIM21-HECT. The antibody was designed as a human IgG Fc region-fused nanobody. To test the protein degradation efficiency of these TRIM21-based constructs, plasmids encoding the d2EGFP, an antibody against d2EGFP, and various Trim21-based constructs were co-transfected into HEK293T cells. The results revealed that TRIM21 (ΔBB) exhibited the most effective degradation performance, followed by TRIM21, whereas TRIM21-RING and TRIM21-HECT performed poorly. A dose-dependent assay confirmed that TRIM21 (ΔBB) showed the best degradation performance even at lower doses. Human papillomavirus (HPV) is a major contributor to the global burden of cancer, and high-risk subtypes are associated with approximately 90% of cervical cancers. Two viral oncoproteins, E6 and E7, play a role in carcinogenesis. Antibodies against E6 and E7 were designed and validated for their ability to degrade these proteins in HEK293T cells and in the cervical cancer cell line CaSki. The results showed that TRIM21 (ΔBB) exhibited the most effective degradation effect, and further investigation revealed that the TRIM21 (ΔBB) construct was able to degrade the E6 and E7 proteins.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024153
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis, and the lack of effective treatment methods accounts for its high mortality. Pancreatic stellate cells (PSCs) in the tumor microenvironment play an important role in the development of PDAC. Previous studies have reported that patients with PDAC are more vulnerable to ferroptosis inducers. To investigate the relationship between PSCs and pancreatic cancer cells, a coculture system is used to further reveal the influence of PSCs on ferroptosis resistance in PDAC using many in vitro and in vivo experiments. Our results show that PSCs promote ferroptosis resistance in pancreatic cancer cells. We further demonstrate that IL15 secretion by PSCs activates the IL15RA-STAT3-GPX4/ACSL3 axis. The simultaneous upregulation of GPX4 and ACSL3 prevents lipid peroxidation and ultimately protects pancreatic cancer cells from ferroptosis both in vitro and in vivo. This study demonstrates that PSCs protect pancreatic cancer cells in a paracrine manner and may indicate a novel strategy for the treatment of PDAC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024126
Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025082
Brain metastases in breast cancer patients are correlated with markedly lower survival rates than extracranial metastases, highlighting the critical necessity for identifying novel therapeutic targets. The functional involvement of differentiation antagonizing nonprotein coding RNA (DANCR) in the pathogenesis of breast cancer brain metastases (BCBMs) has yet to be fully elucidated. Bioinformatics analyses identify DANCR as a potential specific prognostic biomarker of BCBM. CCK-8, transwell, and wound healing assays are performed to examine the effects of DANCR on the proliferation, migration, and invasion of tumors, along with in vivo assays. Mechanistic insights are obtained through quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and dual-luciferase reporter assays. DANCR is markedly upregulated in BCBM and specifically correlates with the prognostic risk of BCBM. DANCR overexpression significantly enhances breast cancer cell proliferation, migration, and invasion. According to low-throughput screening, only the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) consistently varies in parallel with that of DANCR, and PTGS2 silencing reverses DANCR-induced protumor effects in vitro. Additionally, in brain metastatic lesions, PTGS2 expression is also elevated in patients with increased DANCR expression. Mechanistically, DANCR and PTGS2 possess a conserved miR-758-3p response element. DANCR directly binds to and sequesters miR-758-3p, thereby alleviating the suppressive effects of miR-758-3p on both DANCR and PTGS2. When the miR-758-3p binding site on DANCR is mutated, this interaction is completely abolished. DANCR drives BCBM by functioning as a miR-758-3p sponge to upregulate PTGS2. Targeting the DANCR/miR-758-3p/PTGS2 axis represents a promising therapeutic approach.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024170
Doxorubicin (Dox) is widely utilized in the clinical treatment of various cancers. Despite its efficacy, Dox induces numerous adverse effects in humans with significant cardiotoxicity, posing a major limitation to its use. Saussurea involucrata injection (SII), derived from Saussurea involucrata, exhibits notable anti-inflammatory and anti-oxidative stress properties. However, its potential protective effects against Dox-induced cardiotoxicity (DIC) remain unexplored. In this study, we investigate the ability of SII to mitigate DIC and elucidate the underlying mechanisms through experimental research and network pharmacology analysis. Results from both in vitro and in vivo experiments reveal that SII treatment significantly improves Dox-induced cardiac dysfunction, reducing pathological alterations and fibrosis in cardiomyocytes. Moreover, SII has cardioprotective effects by diminishing the inflammation, oxidative stress, and apoptosis triggered by Dox. Network pharmacological analysis further shows that SII downregulates P53 protein expression by activating the AKT/MDM2 signaling pathway, thus attenuating DIC. In conclusion, this study confirms that SII mitigates DIC through downregulation of the AKT/MDM2/P53 signaling pathway, suggesting a promising therapeutic strategy for alleviating DIC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024109
Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant down-regulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261602
The n-butanol fraction of the ethanol extract of Patrinia villosa (Thunb.) Juss. was subjected to systematic phytochemical investigation using silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Fourteen compounds were isolated and structurally elucidated by comprehensive spectroscopic analysis. Two previously undescribed acyclic monoterpenoids, (2E,5R,6R)-5,8-dihydroxy-2,6-dimethyl-2-octenoic acid (1) and (2E,5R,6R)-8-acetoxy-5-hydroxy-2,6-dimethyl-2-octenoic acid (2), were named patrivic acid B and 8-acetylpatrivic acid B, respectively. The remaining twelve known compounds were identified as (2E,6R)-8-hydroxy-2,6-dimethyl-2-octenoic acid (3), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one (4), ethyl chlorogenate (5), ethyl caffeate (6), dihydrosyringenin (7), 7S,8S-threo-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (8), (+)-isolariciresinol (9), (7S,8R)-dihydrodehydrodiconiferyl alcohol (10), ceplignan (11), (+)-syringaresinol (12), salicifoliol (13), and 5-hydroxy-4-(4-hydroxyphenyl)-2(5H)-furanone hydroxybutenolide (14). Compounds 3, 4, 10, 11, and 14 were isolated from P. villosa for the first time. Anti-inflammatory activity was assessed by measuring nitric oxide (NO) inhibition in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. At 50 μmol/L, compounds 1 and 2 exhibited NO inhibition rates of (6.16 ± 1.41)% and (11.11 ± 2.10)%, respectively, indicating no significant anti-inflammatory activity. This study expands the chemical diversity of P. villosa and provides a foundation for further pharmacological exploration of its acyclic monoterpenoid constituents.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261621
This bibliometric investigation systematically maps the research landscape and emerging frontiers of sinomenine, an alkaloid derived from Sinomenium acutum, Diploclisia chinensis, and S. scutum. A comprehensive search of CNKI and Web of Science yielded 710 Chinese and 471 English publications, which were screened via NoteExpress and analyzed using Excel, CiteSpace, and VOSviewer. Publication trends, national distribution, institutional and author networks, and keyword co-occurrence were visualized. China dominates the field, with international attention rising annually. Core research teams have formed, yet collaboration remains largely intra-institutional or regional, with minimal cross-regional integration. Both Chinese and English literature converge on sinomenine's anti-arthritis pharmacological mechanisms, while Chinese studies additionally emphasize extraction, quality standards, and formulation development. The analysis identifies three future breakthrough dimensions: multi-omics-driven integration employing spatial transcriptomics and single-cell sequencing to dissect the drug-host-microbiome network; precision medicine-oriented drug delivery innovations, including microenvironment-responsive nanocarriers and smart hydrogels for targeted controlled release; and clinical expansion into neurodegenerative diseases and organ fibrosis with internationally compliant trials. Establishing a synergistic 'discovery-formulation-clinical validation' framework is recommended to accelerate sinomenine's translation from traditional herbal component to modern precision therapeutic, offering a paradigm for traditional Chinese medicine internationalization.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261615
Ulcerative colitis (UC) remains a clinical challenge due to inadequate mucosal healing and high relapse rates. This study investigates the therapeutic efficacy of schisandrin B (Sch B) in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced rat model of UC, focusing on the interplay between autophagy and pyroptosis. SD rats were randomized into control, model, mesalazine (100 mg/kg), and Sch B low-, medium-, and high-dose (10, 20, 50 mg/kg) groups (n=10 per group). After 14 days of treatment, disease activity index (DAI), colon length, and colon mucosa damage index (CMDI) were assessed. Histopathology, serum cytokine levels (TNF-α, IL-6, IL-1β), and protein expression of autophagy markers (Beclin-1, LC3B, ATG16L1, p62) and pyroptosis pathway components (NLRP3, Caspase-1, GSDMD) were evaluated. Sch B significantly ameliorated weight loss, hematochezia, and colon shortening (P<0.05, 0.01), reduced DAI and CMDI scores, and attenuated mucosal edema, ulceration, and inflammatory infiltration. Serum IL-6, TNF-α, and IL-1β levels were markedly decreased (P<0.05, 0.01). Sch B upregulated Beclin-1 and increased LC3-II/I ratio (P<0.01), while downregulating ATG16L1, p62, NLRP3, Caspase-1, and GSDMD (P<0.05, 0.01). These findings indicate that Sch B restores autophagic flux homeostasis, thereby suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing pro-inflammatory cytokine release. The normalization of autophagic flux is a critical upstream mechanism for Sch B's inhibition of colonic epithelial pyroptosis, offering a multi-target therapeutic strategy for UC.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05095-1
Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are promising for cellular therapy due to their accessibility, low ethical concerns, and immunomodulatory and tissue repair capacities. However, heterogeneity during in vitro expansion poses quality control challenges. Methods: Two fetal umbilical cords were obtained; primary UC-MSCs were isolated and passaged continuously. Cells were harvested for single-cell RNA sequencing; 78,178 cells and 14 subpopulations were analyzed. Validation used in vitro assays and in vivo studies. Results: Mid-passage UC-MSCs showed superior functional performance based on differential gene expression and functional enrichment. An optimal subpopulation (C8) was identified by holistic evaluation of stemness, hematopoietic support, and immunomodulation. NOTCH signaling was enriched in C8, with NOTCH2 as the dominant receptor. MLPH and LPXN were identified as signature markers; MLPHhighLPXNhigh UC-MSCs displayed higher hematopoietic support and immunosuppression than MLPHlowLPXNlow cells. Conclusions: Mid-passage UC-MSCs are favorable for clinical use. The subpopulation with high NOTCH activity exhibits enhanced hematopoietic support and immunosuppression. MLPH and LPXN are ideal markers for isolating this functional subpopulation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21278
BACKGROUND: Previous studies have shown that knockdown of β-catenin can inhibit the osteogenic differentiation of human bone marrow mesenchymal stem cells and reduce the expression of TRIB3. Serum containing Compound Kidney-Invigorating Granules can promote the expression of β-catenin and TRIB3 in human bone marrow mesenchymal stem cells, and induce human bone marrow mesenchymal stem cells to differentiate into osteogenic cells. OBJECTIVE: To further explore the mechanism of Compound Kidney-Invigorating Granules in a mouse model of osteoporosis based on the TRIB3/β-catenin axis. METHODS: 8-week-old female C57BL/6 mice were randomly divided into the following experimental groups: blank control, sham operation, model, and low-, medium-, and high-dose Compound Kidney-Invigorating Granules groups, and positive drug group. Except for the blank control and sham operation groups, bilateral ovariectomy was performed to establish an osteoporosis mouse model. One week after modeling, mice in the low-, medium-, and high-dose groups were intragastrically administered 7.05, 14.1, and 28.2 g/kg Compound Kidney-Invigorating Granules, respectively; the blank control, sham operation, and model groups received an equal volume of normal saline once daily; the positive control group received 1.53 mg/kg alendronate sodium once weekly. After 12 weeks of administration, Micro-CT was used to detect changes in femoral bone microarchitecture; hematoxylin-eosin staining and Masson staining were used to detect pathological changes in the femur; Western blot was used to detect the expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin in bone tissue. RESULTS AND CONCLUSION: Compared with the blank control and sham operation groups, the model group showed sparse bone trabeculae and significantly increased empty lacunae; the protein expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin were significantly decreased (P < 0.05). Compared with the model group, the medium- and high-dose Compound Kidney-Invigorating Granules groups showed more complete and regular bone trabeculae, and the protein expression levels of TRIB3, β-catenin, alkaline phosphatase, and osteopontin were significantly upregulated (P < 0.05). These results indicate that Compound Kidney-Invigorating Granules exert a therapeutic effect on osteoporosis model mice, suggesting that the formula may act through the TRIB3/β-catenin axis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21367
BACKGROUND: Extracorporeal shock wave therapy, as a non-invasive and non-invasive treatment technique, is widely used in various fields. Currently, there is no systematic analysis of the latest research status, hot topics, and development trends in this field. OBJECTIVE: To analyze the research status, hotspots, and trends of extracorporeal shock wave therapy using bibliometric visualization software over the past 10 years. METHODS: Relevant literature in the field of extracorporeal shock wave therapy was retrieved from the Web of Science core database from January 1, 2015 to December 31, 2024. CiteSpace was used for analyzing publication volume, collaborations among countries/regions, institutions, and authors, citation analysis of journals and co-cited literature. Additionally, keyword co-occurrence, clustering, and burst analyses were conducted, and visualized knowledge maps were generated. RESULTS AND CONCLUSION: A total of 1 641 articles were included. The number of publications in the field of extracorporeal shock wave therapy is generally on the rise over the past 10 years. China, the United States, and Italy are the top three countries in terms of publication volume, while Chang Gung University, the University of California, and Harvard University are the top three research institutions. A total of 280 journals published articles related to extracorporeal shock wave therapy, among which Clinical Orthopaedics and Related Research was the most cited journal, and PLoS One had the highest centrality. The author with the highest publication volume was Wang, Ching-Jen from Chang Gung University, and there was little collaboration among high-yield authors and their research groups. The hot keywords in this field were mainly double-blind, pain, erectile dysfunction, plantar fasciitis, lateral epicondylitis, etc. Burst keywords included rabbit, ischemia, myocardial infarction, fasciopathy, muscle spasm, and erectile function, showing diversified research directions. Extracorporeal shock wave therapy is a non-invasive and safe treatment method. Pain management, musculoskeletal system diseases, and urological-related diseases are the research hotspots in the field of extracorporeal shock wave therapy in the past 10 years, and research on related mechanisms is also a focus of interest. Future research directions may focus on standard parameter research and long-term efficacy verification of extracorporeal shock wave therapy.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21362
BACKGROUND: With an increasing understanding of the health benefits of exercise, research on the mechanisms of exercise intervention has become a focal point. Traditional studies rely on in vivo animal models or multi-omics techniques to indirectly infer exercise intervention mechanisms, but the research is not in-depth enough, and many disease models cannot achieve the prescribed exercise intensity. Therefore, in vitro cell-based exercise environment simulation techniques are of particular significance. Existing technologies primarily focus on the replication of single signals, failing to comprehensively simulate the interaction of multi-dimensional signals during exercise, which limits the understanding of exercise adaptation mechanisms. OBJECTIVE: To explore the technological advancements in in vitro cell-based exercise environment simulation, analyze the advantages of existing signal simulation techniques, and propose a new framework integrating multi-dimensional signals to promote the precise replication of exercise mechanisms and application research in related fields. METHODS: This study conducted a search in the PubMed and Web of Science databases using keywords such as Exercise, Physiology, Molecular Signals, Myokines, Exerkines, etc. After initial screening and removal of duplicates, 5,046 relevant articles were identified, and 99 were finally included after further screening. RESULTS AND CONCLUSION: Existing in vitro cell exercise simulation techniques have made some progress in simulating specific attributes of exercise (e.g., mechanical stretching, electrical signals), but they still fail to fully replicate the multi-dimensional signal interactions during exercise. By integrating multiple signals such as mechanical forces, electrophysiological stimuli, and biological factors, future simulation technologies are expected to more realistically reproduce the effects of exercise on cellular metabolism, gene expression, and phenotypic remodeling, providing a more precise experimental platform for studying exercise mechanisms. Furthermore, innovations and optimizations in in vitro exercise simulation technologies will provide important support for sports medicine, drug development, and regenerative medicine.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21341
BACKGROUND: Collagen triple helix repeat-containing protein 1 (CTHRC1) is a positive regulator of bone formation. However, its role and underlying mechanisms in periodontal ligament stem cells (PDLSCs) remain unclear. OBJECTIVE: To investigate the effects of CTHRC1 on the proliferation and osteogenic differentiation of PDLSCs and its mechanism of action. METHODS: Human PDLSCs were isolated and cultured in vitro, and cells were transfected with a lentiviral vector overexpressing CTHRC1. The effect of CTHRC1 overexpression on the proliferation activity of PDLSCs was determined by CCK-8 assay and flow cytometry. The effect of CTHRC1 overexpression on the osteogenic differentiation of PDLSCs was determined by alkaline phosphatase (ALP) activity and Alizarin Red staining. Western blot was used to detect the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) after CTHRC1 overexpression. After blocking the ERK1/2 signaling pathway, the expression of osteogenic differentiation-related factors Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and Osterix was detected by Western blot and qRT-PCR. RESULTS AND CONCLUSION: CCK-8 and flow cytometry results showed that CTHRC1 overexpression promoted the proliferation of PDLSCs. ALP activity and Alizarin Red staining showed that CTHRC1 overexpression promoted the osteogenic differentiation of PDLSCs. Western blot results showed that CTHRC1 overexpression activated the ERK1/2 signaling pathway. Western blot and qRT-PCR results showed that CTHRC1 overexpression promoted the expression of Runx2, OCN, and Osterix at both protein and mRNA levels. When the ERK signaling pathway was inhibited by the specific inhibitor PD98059, the upregulation of osteogenic-related factors was partially suppressed. These results suggest that overexpression of CTHRC1 can promote the proliferation and osteogenic differentiation of PDLSCs, and its osteogenic differentiation effect may be related to the activation of the ERK1/2 signaling pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21343
BACKGROUND: The occurrence of diabetic encephalopathy may be closely related to neuronal aging, but its underlying molecular mechanism is not fully understood. Therefore, exploring the role of neuronal senescence in diabetic encephalopathy is of great significance for further revealing the pathogenesis of diabetic encephalopathy. OBJECTIVE: To investigate the effect and mechanism of emodin on senescence of HT-22 cells under high glucose conditions. METHODS: HT-22 cells were divided into control group (glucose concentration 25 mmol/L), high glucose group (glucose concentration 55 mmol/L), and high glucose + emodin group (glucose concentration 55 mmol/L, emodin concentration 100 µmol/L) and cultured for 48 h. The growth state of cells in each group was observed under microscope; CCK-8 assay was used to detect cell viability; ELISA was used to detect telomerase reverse transcriptase activity; RT-qPCR and western blot were used to detect the expression of senescence-related proteins P53, P21, and P16; immunofluorescence, RT-qPCR and western blot were used to detect the expression of lamin A/C. RESULTS AND CONCLUSION: Compared with the control group, the high glucose group showed obvious growth inhibition under microscope, characterized by decreased cell number, increased cell volume, and flattened morphology; compared with the high glucose group, the high glucose + emodin group showed significantly increased cell number and more regular morphology. Compared with the control group, cell viability was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, cell viability was significantly increased in the high glucose + emodin group (P < 0.0001). Compared with the control group, telomerase reverse transcriptase activity was significantly decreased in the high glucose group (P < 0.001). Compared with the control group, the expression levels of P53, P21, and P16 were significantly increased in the high glucose group (P < 0.05); compared with the high glucose group, the expression levels of P53, P21, and P16 were significantly decreased in the high glucose + emodin group (P < 0.05). Compared with the control group, the expression level of lamin A/C was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, the expression level of lamin A/C was significantly increased in the high glucose + emodin group (P < 0.05). The results indicate that emodin may slow down the senescence of HT-22 cells induced by high glucose by upregulating the expression of lamin A/C.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21338
BACKGROUND: Exosomes derived from mesenchymal stem cells play an important role in regulating apoptosis, promoting cell regeneration, and improving the wound microenvironment, making them a hot research topic in the treatment of diabetic foot ulcers. OBJECTIVE: To explore the clinical application value of exosomes derived from human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers. METHODS: A retrospective analysis was conducted on the data from 72 patients with diabetic foot ulcers treated between May 2022 and April 2025. Thirty-six patients received treatment with exosomes derived from human umbilical cord mesenchymal stem cells (observation group), and 36 patients were managed with vacuum-assisted closure therapy (control group). Ulcer healing rate, incidence of adverse events, serum inflammatory markers, growth factor levels, total wound healing time, and ulcer recurrence rate during follow-up were compared between the two groups after 2 weeks of treatment. RESULTS AND CONCLUSION: (1) After 2 weeks of treatment, the ulcer healing rate in the observation group (48.03±6.12)% was significantly higher than that in the control group (30.13±6.38)%, with a significant difference (P < 0.05). (2) Ulcers healed in both groups, with healing time in the observation group (30.42±2.30) d significantly shorter than that in the control group (43.94±3.46) d (P < 0.05). (3) The incidence of adverse events during treatment was 13.89% in the control group and 19.44% in the observation group, with no significant difference (P > 0.05). (4) Serum levels of interleukin-6, C-reactive protein, and procalcitonin decreased significantly in both groups, with a greater decrease in the observation group (P < 0.01); serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor increased significantly in both groups, with a greater increase in the observation group (P < 0.01). (5) After ulcer healing, the observation group was followed for an average of 9.4 months, with 5 cases of ulcer recurrence; the control group was followed for an average of 9.8 months, with 10 cases of recurrence. The recurrence rate in the observation group was significantly lower than that in the control group (13.9% vs. 27.8%, P < 0.05). These results indicate that compared with vacuum-assisted closure therapy, application of exosomes derived from human umbilical cord mesenchymal stem cells for repairing diabetic foot ulcers can effectively inhibit inflammation, promote ulcer healing, and reduce recurrence rate without increasing the risk of related adverse events, demonstrating both efficacy and safety.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21398
BACKGROUND: Moxibustion has been demonstrated as an effective therapeutic approach for atopic dermatitis, yet its underlying mechanisms remain to be further elucidated. OBJECTIVE: To investigate the mechanisms of moxibustion intervention in atopic dermatitis using proteomics technology. METHODS: Thirty-four Sprague-Dawley rats were randomly divided into three groups: a model group (n=12), a moxibustion group (n=12), and a blank group (n=10). The first two groups were induced to develop an atopic dermatitis model using 2,4-dinitrochlorobenzene. Following successful modeling, the moxibustion group received moxibustion therapy with moxa sticks applied to the Ashi point for 30 minutes per session, maintaining a local temperature of (43±1) °C, administered every other day over a 14-day intervention period. The model group and blank control group underwent restraint and fixation procedures of the same duration and intensity. Skin lesion severity after modeling was evaluated using the Eczema Area and Severity Index. Proteomic analysis of rat skin tissue was performed using a data-independent acquisition approach on a high-performance liquid chromatography-tandem mass spectrometry platform. Mass spectrometry data processing, protein identification, differential protein expression analysis, functional annotation, and bioinformatics analyses were conducted using MaxQuant, Perseus software, DAVID, STRING, and Cytoscape. RESULTS AND CONCLUSION: After moxibustion treatment, the skin lesion score of atopic dermatitis model rats was significantly lower than that of the model group (P < 0.05), indicating successful modeling. Moxibustion reversed the upregulation of 28 differentially expressed proteins and the downregulation of 40 differentially expressed proteins in the model group. Bioinformatics analysis indicated that the main signaling pathways involved in atopic dermatitis pathogenesis include neuroactive ligand-receptor interaction, viral protein interaction with cytokine and cytokine receptor, inflammatory mediator regulation of TRP channels, and neutrophil extracellular trap formation. Among these, the expression regulation of integrin β3 and β-1,4-galactosyltransferase proteins may be most relevant to the pathogenesis of atopic dermatitis. The mechanisms of moxibustion in treating atopic dermatitis mainly involve herpes simplex virus 1 infection, olfactory transduction, influenza A, steroid hormone biosynthesis, and other infection- or immune-related signaling pathways. The most relevant proteins include nuclear factor κB subunit 1, major histocompatibility complex protein, RT1-Bb, Jak1, and Cdk6. These findings suggest that moxibustion exerts a multi-target, multi-pathway, and multi-channel intervention effect on atopic dermatitis, reversing the inflammatory response caused by atopic dermatitis and exerting anti-inflammatory and antioxidant effects.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21459
BACKGROUND: Odanacatib effectively exerts anti-inflammatory effects and promotes alveolar bone repair in periodontitis-affected areas. However, multiple injections are required to ensure efficacy, which is cumbersome. OBJECTIVE: To prepare an odanacatib-loaded microsphere-gel composite sustained-release carrier and characterize its biocompatibility. METHODS: (1) Poly(lactic-co-glycolic acid) microspheres loaded with different masses of odanacatib (denoted as ODN-MS) were prepared by emulsion-solvent evaporation method. Based on drug loading and encapsulation efficiency, microspheres prepared with 5 mg odanacatib and 40 mg PLGA were selected for subsequent experiments. Different masses of ODN-MS were mixed with methacrylated gelatin (GelMA) solution to prepare gel composite sustained-release carriers (denoted as ODN-MS-Gel), with ODN-MS mass concentrations of 250 and 500 μg/mL. The microstructure and in vitro drug release properties of ODN-MS and 250 μg/mL ODN-MS-Gel were characterized. (2) Rabbit bone marrow mesenchymal stem cells (BMSCs) were cultured with extracts of GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 and 500 μg/mL ODN-MS-Gel. CCK-8 assay was used to detect cell proliferation. Rabbit BMSCs were cultured with extracts of GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 μg/mL ODN-MS-Gel. Live/dead staining was used to detect cell viability. Rabbit BMSCs were seeded on GelMA gel, PLGA microsphere-loaded gel composite sustained-release carrier, and 250 μg/mL ODN-MS-Gel. Phalloidin staining and scanning electron microscopy were used to observe cell adhesion. RESULTS AND CONCLUSION: (1) Under optical microscope, ODN-MS were spherical, uniformly distributed, and without agglomeration. Scanning electron microscopy showed that ODN-MS surface had fine porous structure; 250 μg/mL ODN-MS-Gel hydrogel had porous structure, and ODN-MS were distributed in the porous structure. Both ODN-MS and 250 μg/mL ODN-MS-Gel could achieve sustained drug release, and the 250 μg/mL ODN-MS-Gel system released drug more gently, achieving dual sustained-release effect. (2) CCK-8 assay showed that 250 and 500 μg/mL ODN-MS-Gel extracts could promote the proliferation of rabbit BMSCs. Live/dead staining showed that 250 μg/mL ODN-MS-Gel extract did not affect the viability of rabbit BMSCs. Phalloidin staining and scanning electron microscopy showed that compared with the other two materials, 250 μg/mL ODN-MS-Gel promoted the adhesion of rabbit BMSCs. These results indicate that ODN-MS-Gel can achieve sustained release of odanacatib and has good biocompatibility.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21685
BACKGROUND: Single condylar knee arthroplasty is an effective method to treat unilateral compartment knee osteoarthritis. As an advanced biomechanical research tool, finite element analysis provides important support for the prosthesis design and surgical planning of single condylar knee arthroplasty and the biomechanical characteristics of knee joint after unicompartmental knee arthroplasty. OBJECTIVE: To explore the application progress of finite element analysis in unicompartmental knee arthroplasty, including the optimization of unicompartmental knee arthroplasty prosthesis design, surgical planning and biomechanical characteristics of knee joint after unicompartmental knee arthroplasty. METHODS: The first author used PubMed, CNKI, and WanFang for articles published from database inception to August 2025. English search terms were "FEA, UKA, knee osteoarthritis, knee joint, femoral component, tibia component, biomechanics, ligament of knee joint." Chinese search terms were "finite element analysis, unicompartmental knee arthroplasty, knee osteoarth..." (truncated in original). RESULTS AND CONCLUSION: ①Optimization of prosthesis design: Finite element analysis can provide precise data guidance for the optimization of unicompartmental prosthesis design by constructing different unicompartmental prosthesis replacement models and analyzing stress distribution under different prosthesis structures; ②Precise surgical planning: Finite element analysis can precisely predict the effects of different osteotomy schemes on knee biomechanics, including tibial posterior slope, joint line position, and lower limb alignment, providing theoretical guidance for surgeons to choose the best surgical plan, improve surgical accuracy, reduce complication risk, and enhance long-term prosthesis survival; ③Using finite element analysis to predict biomechanical characteristics after unicompartmental replacement can non-invasively and predictively simulate postoperative knee mechanical behavior, including ligament tension, cartilage contact pressure, and bone strain distribution, solving mechanical details that two-dimensional imaging cannot capture.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21603
BACKGROUND: In recent years, the convergence of materials science and biomedical engineering has opened new avenues for diabetic foot wound treatment. Novel biomaterials such as multifunctional hydrogels, tissue engineering scaffolds, and nanoparticle systems have become a research hotspot. OBJECTIVE: To analyze, through bibliometric analysis, the design principles and biological functions of novel materials used in diabetic foot wound treatment, their potential in addressing the complex pathological challenges of diabetic foot, and to forecast future directions and challenges in this field. METHODS: We searched the Web of Science database for literature on novel materials for diabetic foot wounds from database inception to June 2025, and used CiteSpace software for bibliometric visualization analysis. RESULTS AND CONCLUSION: From 1979 to 2025, the number of publications in the field of novel materials for diabetic foot wound treatment showed an overall fluctuating upward trend, with explosive growth from 2022 to 2025. The United States ranked first with 602 publications, followed by China (284 publications) and India (166 publications). By publication count, Sichuan University had the most publications, followed by Tehran University of Medical Sciences; by citation impact, Sichuan University had the highest total citation impact, followed by Nankai University. West China Hospital ranked first in publication count, followed by Beth Israel Deaconess Medical Center and Thomas Jefferson University Hospital; by citation impact, West China Hospital had the highest impact, followed by Shanghai Ninth People's Hospital and Thomas Jefferson University Hospital. Among companies, Success Bio-Tech Co. Ltd, Engineering Software Research and Development Inc, and Foot and Ankle Associates of Central Illinois LLC each had 2 publications, ranking first; by citation impact, Organogenesis Inc had the highest impact, followed by Food Industry Research Co. The journal Wounds had the most publications (96), followed by Foot Ankle Int (40) and Cureus (38). Among authors, Bus, Sicco A had the most publications (12), followed by Lázaro-Martínez, José Luis (8); by citation impact, GBD 2021 US Burden of Disease and Forecasting Collaborators, GBD 2021 Diabetes Collaborators, GBD 2021 US Obesity Forecasting Collaborators, GBD 2021 US Burden of Disease Collaborators, GBD 2021 Adult BMI Collaborators, GBD 2021 Adolescent BMI Collaborators, and GBD 2021 Causes of Death Collaborators had the highest impact. Keywords: diabetic foot; diabetic foot wound; diabetic foot ulcer; biomaterials; dressing; visualization analysis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04898-6
Background: Bionic treatment strategies for spinal cord injury (SCI) seek to emulate natural morphological structures and regeneration processes. Zebrafish, possessing remarkable regenerative capabilities, were employed to investigate the regulatory pattern of spinal vascular regeneration following SCI, aiming to inform bionic SCI therapy development. Methods: Live imaging monitored zebrafish spinal perineural vessel plexus (PNVP) formation, which occurs at approximately 18 days post-fertilization (dpf). SCI modeling was timed at 19 dpf. Radial glia (RGs) in Tg(gfap:NTR-mCherry) reporter fish were chemically ablated using metronidazole (Mtz) or nitrofuropyrinol (Nfp). Vascular repair patterns, injured area vascular coverage, and endothelial cell (EC) counts were assessed. Vegfaa expression profiles and public single-cell sequencing data (GSE202429) were analyzed to postulate downstream pathways, validated with specific inhibitors. Results: RGs were successfully ablated (>90% efficiency) with 10 mM Mtz or 1.25 µM Nfp. In Mtz/Nfp+SCI groups, vascular coverage and EC numbers were significantly reduced versus DMSO+SCI controls. Vegfaa reporter signal declined notably in the injured region post-ablation. Inhibitor experiments supported involvement of Vegfa-PI3K/Akt-mTOR and Notch signaling pathways. Conclusion: RGs play a pivotal role in spinal vascular regeneration after SCI in zebrafish, likely via Vegfa-PI3K/Akt-mTOR and Notch pathways. Mimicking zebrafish RG pro-regenerative functions may achieve pro-vascular repair in mammals after SCI.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025232
Midnolin (MIDN) is a newly recognized master regulator that drives ubiquitin-independent proteasomal degradation, yet the mechanisms governing its own turnover remain enigmatic. Here, we demonstrate that MIDN is ubiquitinated and identify RNF126 as the cognate E3 ligase. RNF126 physically associates with MIDN and catalyzes its ubiquitination, and mass spectrometry mapping reveals that this process occurs primarily at non-canonical cysteine, serine, and threonine residues (C230, C236, S237, T239, and S241) rather than at lysine residues. This non-classical ubiquitination targets MIDN for 26S-proteasomal degradation. In vivo dissection of the RNF126-MIDN axis shows that it governs EGR1 abundance and, consequently, the tumor-suppressor proteins PTEN and p53, thereby restraining the progression of testicular germ-cell tumors (TGCTs). Our findings reveal an unappreciated layer of MIDN regulation and identify the RNF126-MIDN ubiquitination cascade as a potential therapeutic vulnerability in TGCTs and related malignancies.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026066
Fibroblast growth factor 10 (FGF10) plays a critical role in ocular surface homeostasis, yet its function in early meibomian gland (MG) development remains largely unknown. Here, we generated an Fgf10 mutant mouse model with deletion of exon 2, leading to loss of function. Adult Fgf10+/− mice exhibited lacrimal gland agenesis, smaller Harderian glands, increased corneal fluorescein staining, and reduced tear volume. Histological analysis revealed multilayered hyperplastic epithelium in Harderian glands and MG atrophy. Time-series Oil Red O staining showed shorter, thinner, and disordered MGs in Fgf10+/− mice at P14 and P21, with unrecoverable defects at P135. RNA sequencing of MGs at P14 and P21 revealed significant dysregulation of macrophage-related genes and immune-related pathways, including antigen processing and presentation and macrophage chemotaxis. Using Cx3cr1GFP/+ reporter mice, we observed a significant reduction in CX3CR1-positive cells in the inter-acinar stroma of Fgf10+/− MGs. Pharmacological ablation of CSF1R-expressing cells with PLX3397 in wild-type mice recapitulated the MG developmental defects, confirming that FGF10 acts through immune cells to regulate MG development. Collectively, our findings establish that FGF10 haploinsufficiency leads to severe glandular malformations, impaired tear production, and compromised corneal integrity, highlighting the essential role of FGF10 in postnatal MG development and immune cell regulation.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025145
Angiopoietin-like 4 (ANGPTL4) is elevated in wound tissue and contributes to wound healing, but the mechanisms remain unclear. This study demonstrates that ANGPTL4 expression is significantly increased in epidermal stem cells (EpSCs) in the periwound epidermis during murine wound healing. Increased Angptl4 expression positively correlates with elevated levels of tumor growth factor-α, interleukin-1β, epidermal growth factor, nerve growth factor, fibroblast growth factor 7, and transforming growth factor-β1, each of which induces Angptl4 in EpSCs. RNA sequencing of EpSCs from wild-type and Angptl4 knockout (Angptl4–/–) mice reveals altered expression of cell cycle and proliferation genes, including decreased cyclin E2/A2/B1 and cyclin-dependent kinase 1 (Cdk1), increased Cdk inhibitor 2a (Cdkn2a) and Cdkn2b, and reduced prolactin (PRL) family members Prl2a1, Prl8a1, Prl8a9, and Prl8a6. Mechanistically, ANGPTL4 stimulates EpSC proliferation via PRL8a6-mediated upregulation of cyclins A2/E2/B1 and Cdk1, downregulation of Cdkn2a, and acceleration of G1 to S and G2 phase progression. In vivo, Prl8a6 mRNA is upregulated by ANGPTL4 in mouse periwound tissue during healing. Knockdown of Angptl4 or Prl8a6 impairs EpSC proliferation and delays re-epithelialization. These findings establish that after skin injury, proinflammatory cytokines and growth factors stimulate Angptl4 in EpSCs, and ANGPTL4 promotes EpSC proliferation by increasing Prl8a6, thereby accelerating wound re-epithelialization.
Chinese Journal of Tissue Engineering Research•2025•DOI: 10.12307/2025.20219
BACKGROUND: Adeno-associated virus (AAV) gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years. However, given the complexity of osteoarthritis pathogenesis, single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results. Previous studies have shown that nuclear factor κB could promote the inflammatory pathway in osteoarthritic chondrocytes, and bone morphogenetic protein 4 (BMP4) could promote cartilage regeneration. OBJECTIVE: To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment. METHODS: Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared. Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells. The experiments were divided into five groups: PBS group; osteoarthritis group; AAV-BMP4 group; AAV-p65shRNA group; and BMP4-p65shRNA 1:1 group. Samples were collected at 4, 12, and 24 weeks postoperatively. Tissue staining, including safranin O and Alcian blue, was applied after collecting articular tissue. Then, the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo. RESULTS AND CONCLUSION: The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment. Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis (P < 0.05). In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage (P < 0.05). In the present study, we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions. Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis. This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment. These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025077
Necroptosis, a lytic form of programmed cell death driven by the RIPK1/RIPK3/MLKL axis, is implicated in inflammatory pathologies including systemic inflammatory response syndrome and acute pancreatitis. Andrographolide (Andro), a diterpene lactone from Andrographis paniculata, exhibits anti-inflammatory efficacy, but its effect on necroptosis remains undefined. Here, Andro inhibited necroptosis in cellular models induced by lipopolysaccharide (LPS) plus IDN-6556 or TNF-α, LCL-161 (Smac mimetic), and IDN-6556. Andro suppressed phosphorylation of RIPK1, RIPK3, and MLKL and blocked necrosome formation. Mechanistically, Andro reduced intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS), preserved mitochondrial membrane potential, and activated the antioxidant transcription factor Nrf2. Upon necroptotic stimulation, mitochondrial proteins Bcl-2 and Bak oligomerized and co-localized with RIPK1, RIPK3, and p-MLKL in necrosomes; Andro prevented this process. Derivatives including dehydroandrographolide, neoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and 14-deoxyandrographolide lacked anti-necroptotic activity and failed to upregulate Nrf2. These findings establish Andro as a specific inhibitor of the RIPK1/RIPK3/MLKL signaling axis, highlighting its therapeutic potential against necroptosis-related disorders.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025102
Influenza A viruses (IAVs) remain a global health burden, with seasonal epidemics causing 290,000–650,000 deaths annually. Licensed antivirals—M2 ion-channel inhibitors, neuraminidase (NA) inhibitors, RNA polymerase inhibitors, and cap-dependent endonuclease inhibitors—are compromised by adaptive mutations, particularly in M2 and NA. We screened approximately 5,500 compounds and identified nanchangmycin as a potent IAV inhibitor with robust in vitro and in vivo antiviral activity. Nanchangmycin exhibits broad-spectrum efficacy against pseudorabies virus, herpes virus, porcine epidemic diarrhea virus, and porcine reproductive and respiratory syndrome virus. Notably, it inhibits oseltamivir-resistant IAV strains in sub-μM ranges and promotes survival of MDCK cells infected with an oseltamivir-resistant strain. Mechanistic studies reveal that nanchangmycin blocks nuclear migration of viral nucleoproteins (NPs), causing NP accumulation in the cytoplasm, particularly within perinuclear endosomes. It acts by blocking endosomal acidification, a step essential for viral uncoating. These findings position nanchangmycin as a promising lead for anti-influenza therapeutics, particularly against oseltamivir-resistant strains.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025062
p62/SQSTM1 is the archetypal selective autophagy receptor, bridging ubiquitinated cargo to LC3 on phagophores. Its abundance is a critical determinant of autophagic flux, yet the E3 ligase governing its turnover remained incompletely defined. Using Flag-p62 Co-IP coupled to mass spectrometry in HEK293T cells, we identified the E3 ligases TRIM25 and ITCH as highest-confidence interactors. Endogenous and ectopic p62 formed complexes with both ligases; GST pull-down confirmed direct binding, and mCherry-TRIM25 co-localized with GFP-p62 in HeLa cytoplasm. In vitro ubiquitination demonstrated that TRIM25, but not ITCH, efficiently ubiquitinates p62. A reconstituted E. coli system mapped fifteen lysine residues, with K7 and K189 validated as the dominant TRIM25-mediated ubiquitination sites. Functionally, TRIM25 destabilized wild-type p62 but not the K7/189R mutant; TRIM25 knockdown stabilized p62 in HeLa and Caski cells. Degradation proceeded primarily via the lysosomal pathway, as bafilomycin (20 nM) but not bortezomib (1 μM) blocked p62 loss. TRIM25 knockdown enhanced GFP-LC3 puncta formation (P < 0.01) and elevated autophagic markers, whereas TRIM25 overexpression suppressed p62-mediated GFP-LC3 puncta (P < 0.05) and autophagy. These data establish TRIM25 as the principal E3 ligase targeting p62 for lysosomal degradation, defining a negative feedback node in selective autophagy with therapeutic implications for cancers and neurodegenerative disorders characterized by p62 accumulation.