Chinese Journal of New Drugs•2025•DOI: 10.1007/s12274-025-1234-5
Dihydromyricetin (DHM) is a flavonoid compound with various pharmacological activities. In this study, the extraction process of DHM from vine tea (Ampelopsis grossedentata) was optimized using response surface methodology (RSM) based on single-factor experiments. The optimal extraction conditions were determined as follows: extraction temperature 70 °C, extraction time 60 min, liquid-to-solid ratio 30:1 mL/g, and ethanol concentration 60%. Under these conditions, the extraction yield of DHM reached 12.35 mg/g, which was close to the predicted value. Furthermore, network pharmacology was employed to explore the potential molecular mechanism of DHM against liver fibrosis. The results indicated that DHM may exert its therapeutic effect by regulating multiple signaling pathways, including PI3K-Akt, MAPK, and TNF signaling pathways. This study provides a scientific basis for the efficient extraction of DHM and its potential application in the treatment of liver fibrosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Background Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Methods Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Results Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04954-1
Neuroinflammation is a key pathogenic factor for neurodegenerative diseases. Mesenchymal stem cell (MSC) transplantation, as a potential strategy for regulating neuroinflammation, has received extensive attention. Our previous research revealed that compared with ordinary MSC, MSC pretreated with tanshinone IIA (TIIA), referred to as TIIA-MSC, exhibited superior anti-neuroinflammatory activity, but the mechanism of action remains unclear. To clarify the underlying mechanism, this study integrated in vitro and in vivo experiments and evaluated the therapeutic effect of TIIA-MSC in a triple-transgenic Alzheimer’s disease mouse model (3×Tg-AD mice) and explored its mechanism of action in a lipopolysaccharide (LPS)-induced BV2 microglial cell inflammation model. The results showed that TIIA-MSC could significantly improve the cognitive function of 3×Tg-AD mice, increase brain glucose metabolism levels, promote the recovery of synaptic and mitochondrial structures, and effectively alleviate neuroinflammatory responses. In vitro experiments further verified the superior inhibitory effect of TIIA-MSC on microglial cell activation and proinflammatory factor release. Mechanistic studies have indicated that the triggering receptor expressed on myeloid cells 2 (TREM2) is the key molecule that mediates this process. The knockdown of TREM2 expression significantly weakened the anti-inflammatory effect of TIIA-MSC, suggesting that TREM2 plays a central role in this process. Further analysis revealed that by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway downstream of TREM2, TIIA-MSC may promote the transformation of the functional state of microglia from mainly proinflammatory to having neuroprotective and repair properties. This study systematically revealed the molecular mechanism by which TIIA-MSC regulate microglial cell phenotypic transformation through the TREM2/PI3K/Akt pathway and exert anti-neuroinflammatory effects, providing new ideas and an experimental basis for expanding the application of MSC in the treatment of neurodegenerative diseases.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04173-0
Background Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication after radical prostatectomy. Conventional treatment approaches have had little success in treating the severe cavernous fibrosis which is a consequence of CNI-ED. Methods Pre-treatment of adipose-derived stem cells with melatonin allows for the extraction of active exosomes (MT-hASC-EVs) from the conditioned medium. The therapeutic effects of MT-hASC-EVs were assessed in a rat model of CNI-ED, and the anti-fibrotic properties were evaluated. MicroRNA sequencing was used to identify specific microRNAs highly expressed in MT-hASC-EVs, and differential microRNAs were screened for regulatory pathways through target gene enrichment analysis. Finally, the conclusions from bioinformatics analysis were validated through in vitro experiments. Results Intracavernous injection of MT-hASC-EVs significantly restored erectile function and reduced the extent of corpus cavernosum fibrosis in the CNI-ED rat model. MT-hASC-EVs promoted the proliferation and anti-apoptotic effects of corpus cavernosum smooth muscle cells (CCSMCs) in vitro. Mechanistically, MT-hASC-EVs inhibit fibrosis by delivering miR-145-5p, which targets TGF-β2/Smad3 axis. Conclusions MT-hASCs-EVs can inhibit cavernous fibrosis and improve erectile function in a rat model of CNI-ED by targeting the miR-145-5p/TGF-β/Smad axis.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04396-1
Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration.
Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group.
Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy.
Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.
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/s13287-024-03741-0
Background Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart. Methods CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.05μM and HRA with 0.1 μM) between day 3-6 of the differentiation process. Engineered heart tissues (EHTs) were generated by assembling hiPSC-CM at high cell density in a low collagen hydrogel. Results In the HRA group, hiPSC-CMs exhibited highest expression of contractile proteins MYH6, MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are marker genes for left ventricular CMs, was also the highest in the HRA group. In terms of EHT, the HRA group displayed the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline, which means it was functionally more similar to the left ventricle. RNAsequencing revealed that the heightened contractility of EHT within the HRA group can be attributed to the promotion of augmented extracellular matrix strength by RA. Conclusion By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHTs with a phenotype similar to that of the left ventricle or right ventricle.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026076
In Arabidopsis, the PPR proteins EMB1006, EMB1270, and EMB976 are all essential for the splicing of plastid clpP1 intron 2 (clpP1.2), although each also targets other distinct RNAs. The precise mechanism underlying their co-ordinated action in clpP1.2 splicing remains unclear. In this study, RNA electrophoretic mobility shift assays, guided by PPR code prediction, confirm that EMB1006 specifically binds to a sequence near the 3′ end of clpP1 exon 2. Additionally, immunoprecipitation coupled with mass spectrometry reveals that EMB1006 forms a complex with EMB1270, EMB976, and CFM2. Direct interactions between EMB1006 and EMB1270 or CFM2 are further supported by yeast two-hybrid (Y2H) and semi-in vivo pull-down assays. However, no direct interactions between EMB976 and EMB1006, CFM2 or EMB1270 are detected by Y2H. Based on these findings and previous evidence that EMB1270 binds to clpP1 intron 2 and interacts with CFM2, we propose a model in which EMB1006 and EMB1270 bind to distinct sites on clpP1 pre-mRNA. Together with CFM2 and possible indirect association with EMB976, they assemble into a protein-RNA complex that facilitates the splicing of clpP1.2 in chloroplasts.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025068
Lysine acetylation has been shown to be an abundant and vital post-translational modification (PTM) that utilizes acetyl phosphate (AcP) as one of the acetyl group donors in bacteria. The pyruvate dehydrogenase (PDH) complex catalyzes the conversion from pyruvate to acetyl coenzyme A (acetyl-CoA). Thus far, the connection between lysine acetylation and pyruvate metabolism has not been thoroughly investigated. In this study, we show that AcP could acetylate Escherichia coli pyruvate dehydrogenase (AceE) in vitro and in vivo, which could be reversed by protein lysine deacetylase (CobB). In vitro treatment of AceE with AcP also causes increased phosphorylation of the protein, whereas deleting ackA does not affect the phosphorylation of the protein. As a result, in vitro treatment of AceE by AcP leads to decreased enzymatic activity. In contrast, deleting ackA leads to increased acetylation and enzymatic activity of AceE, and deleting pta results in the decreased acetylation and enzymatic activity of AceE. As expected, deleting pta in E. coli causes pyruvate accumulation. Although deleting ackA also causes pyruvate accumulation, decreased expression of the two genes involved in pyruvate metabolism (ldhA and poxB) is observed in the mutant, indicating that AcP could affect pyruvate metabolism by other routes in addition to modulating the AceE activity. Thus, our results demonstrate that intracellular AcP could modulate pyruvate metabolism in E. coli. For the first time, a linkage between AcP-mediated protein lysine acetylation, pyruvate dehydrogenase activity, and pyruvate metabolism is established.
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.2025172
Long noncoding RNAs (lncRNAs) are essential in regulating the development and progression of different types of cancer. However, our insights into their impact and mechanisms in papillary thyroid carcinoma (PTC) are still insufficient. In this study, we investigate the effects of the ferroptosis-associated long noncoding RNA LINC02432 on PTC, which recognizes ferroptosis as a critical mechanism in cancer biology and lncRNAs as significant factors in various malignancies. To identify lncRNAs associated with ferroptosis in PTC, we conduct bioinformatics analyses and perform functional assays to evaluate the biological impact of LINC02432 on PTC cells, as well as its relationship with ferroptosis. Mechanistic studies employ methods such as western blot analysis, flow cytometry, and real-time PCR. Our analysis of transcriptome data from TCGA reveals that LINC02432 is the only lncRNA consistently identified by all 10 machine learning methods used, and its expression is significantly downregulated in PTC. Overexpression of LINC02432 in PTC cells inhibits cell proliferation and migration while promoting ferroptosis through inactivation of the NRF2 pathway. LINC02432 knockdown in PTC cells yields the opposite result. These findings highlight the potential of LINC02432 as a tumor suppressor in PTC progression, offering new insights into the mechanisms underlying the development and progression of this malignancy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025075
Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aims to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results reveal that FGF8 promotes LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirm the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. The results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026025
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, represents an extremely aggressive malignancy. The induction of cuproptosis has developed into a favorable therapeutic direction for HCC, considering its strong association with HCC. Sanguinarine (San), a benzophenanthridine alkaloid derived from traditional herbs such as Chelidonium majus L., demonstrates broad-spectrum anticancer activities against various cancer cell types. However, the precise molecular mechanisms underlying its effects in the treatment of HCC remain largely undefined. This investigation seeks to examine the anti-HCC effects of San and to explore the mechanisms underlying these effects through the induction of cuproptosis. In vitro experiments demonstrate that San markedly inhibits the proliferation, movement, and epithelial-mesenchymal transition of HCC cells while enhancing their apoptosis. In vivo, San notably impedes tumor growth and upregulates the cuproptosis signature markers ferredoxin 1 (FDX1), oligomeric dihydrolipoamide S-acetyltransferase (DLAT), and heat shock protein 70 (HSP70) in HCC xenograft tumor models. Mechanistically, San induces proteotoxic stress and cuproptosis in HCC cells by increasing copper concentration, upregulating the expression of FDX1, lipoic acid synthetase (LIAS), HSP70, and lipoylated DLAT aggregation, and simultaneously reducing mitochondrial membrane potential and intracellular glutathione and pyruvate levels. Moreover, the combination of San with copper ionophores (Elesclomol-CuCl2) exhibits synergistic effects in promoting cuproptosis. FDX1 silencing markedly diminishes San-induced suppression of cell proliferation and FDX1 and HSP70 levels in HCC cells. Additionally, molecular docking analysis predicts that San exhibits the highest potential for binding with FDX1. Surface plasmon resonance experiments and cellular thermal shift assay confirm that San strongly interacts with FDX1 and markedly enhances the thermostability of FDX1. In conclusion, our findings indicate that San substantially inhibits the progression of HCC by targeting FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024078
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like (Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p (Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024050
The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024100
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M.tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4+ T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M.tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025017
Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024168
Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis in vivo and in vitro. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024161
Acute lung injury (ALI) is a severe pulmonary disorder of sepsis with high clinical incidence and mortality. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-cysteinyl aspartate specific proteinase 1-gasdermin D (GSDMD)-dependent pyroptosis of alveolar epithelial cells (AECs) has emerged as a crucial contributor to ALI during sepsis. Phillyrin (PHI), a natural lignan isolated from the traditional Chinese herbal medicine Forsythia suspensa, has been shown to have anti-inflammatory, antioxidant and antiviral properties. However, little is known about the protective role and potential mechanism of PHI in sepsis-induced ALI, and it is uncertain whether the protective effect of PHI in sepsis-induced ALI is connected to pyroptosis. This study aims to examine the preventive effects of PHI on sepsis-induced ALI via the inhibition of NLRP3/caspase-1/GSDMD-mediated pyroptosis in AECs. Our findings demonstrate that preadministration of PHI successfully reduces sepsis-induced pulmonary edema, systemic/pulmonary inflammation, and pulmonary histological damage in lung tissues, bronchoalveolar lavage fluid, and the serum of septic mice. Intriguingly, PHI preadministration suppresses sepsis-induced protein expressions of pyroptosis-specific markers, especially their active forms. In vitro assays show that PHI pretreatment also protects type II AECs (MLE-12) from lipopolysaccharide-induced pyroptosis by preventing the activation of the pyroptosis signaling pathway. The results from molecular docking and surface plasmon resonance reveal that PHI has a significant affinity for direct binding to the GSDMD protein, suggesting that GSDMD is a potential pharmacological target for PHI. In conclusion, PHI can prevent sepsis-triggered ALI by effectively suppressing the activation of the canonical pyroptosis signaling pathway and pyroptosis of AECs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024199
The renin-angiotensin system (RAS) is a crucial regulatory mechanism for cardiovascular function. The angiotensin II (Ang II) type 1 receptor (AT1R) is the principal receptor responsible for mediating RAS function. AT1R belongs to the G protein-coupled receptor (GPCR) family and is present in multiple tissues, including vascular smooth muscle, endothelium, heart, brain, kidney, adrenal gland, and adipose tissue. Physiologically, AT1R mediates second messenger signaling through classical G proteins. Ang II binding to AT1R predominantly activates Gq/11, leading to the activation of phospholipase C (PLC), which results in the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG). Then, increased Ca2+ is released from the sarcoplasmic reticulum to mediate the processes of vasoconstriction, enhance cardiac contractility, regulate water‒salt balance, etc. Under pathological conditions, AT1R aberrantly activates G proteins, including mitogen-activated protein kinases (MAPKs: ERK1/2, JNK, and p38MAPK), receptor tyrosine kinases (PDGF, EGFR, and insulin receptor), non-receptor tyrosine kinases [Src, JAK/STAT, and focal adhesion kinase (FAK)], and NADPH oxidase, to influence downstream pathways. This activation exacerbates inflammatory responses, fibrosis, and pathological cardiovascular remodeling. AT1Rs within the nervous system can also induce excessive activity in the sympathetic nervous system, which increases myocardial strain and facilitates the progression of heart failure. Owing to the importance of AT1R in a variety of diseases, greater demands have been placed on the accuracy of AT1R detection. The structural complexity and low immunogenicity of GPCRs pose considerable challenges in the development of specific antibodies. Many commercially available antibodies for GPCRs, such as those against muscarinic and adrenergic receptors, lack specificity. Current studies on AT1R often use these commercial antibodies, but many fail to demonstrate specificity when AT1R-knockdown or AT1R-overexpressing tissues and cells are tested. This study aims to specifically validate six newly available commercial AT1R antibodies (Supplementary Table S1). Using AT1R global knockout SD rats, cardiomyocyte conditional AT1R knockout C57BL/6N mice, AT1R-overexpressing CHO stable-transformed cell lines and AT1R-overexpressing HEK293 cells, we assessed AT1R expression and localization through receptor-ligand binding assays, RT-PCR, western blot analysis, and immunocytochemistry. Materials and methods are available in Supplementary Materials and Methods. To verify the specificity of the antibody, we generated AT1R-global knockout SD rats (AT1R-KO) using CRISPR-Cas9 technology. Agarose gel electrophoresis revealed bands at approximately 470 bp for AT1R-KO rats and 531 bp for wild-type (WT) rats, confirming successful AT1R knockout at the gene level (Figure 1A). RT-PCR analysis of vascular tissue RNA revealed the absence of AT1R in AT1R-KO rats (Figure 1B). Ligand-receptor binding assays revealed significantly less 125I-Ang II binding to vascular tissue proteins in AT1R-KO rats than in WT rats (Figure 1C). Additionally, primary cardiomyocytes extracted from 0–3-day-old WT and AT1R-KO neonatal rats presented a significant increase in beating rate upon Ang II stimulation in WT rats, whereas no response was observed in AT1R-KO rats (Figure 1D). These results confirmed successful AT1R global knockout in AT1R-KO rats. AT1R-KO rats were thus utilized to verify the specificity of AT1R antibodies (A14201, 25343-1-AP, and 66415-1-Ig). Western blot analysis was conducted on protein extracts from the heart, vascular, liver, and kidney tissues of WT and AT1R-KO rats. Under room temperature denaturation conditions, the A14201 antibody detected AT1R bands at the expected molecular weight (42 kDa) in all tissues from WT rats, the 25343-1-AP antibody detected AT1R in heart and kidney tissues, and the 66415-1-Ig antibody detected AT1R only in the heart tissues. Compared with WT control rats, the A14201 antibody revealed a reduction in AT1R protein expression in AT1R-KO rats.
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•2025•DOI: 10.3724/abbs.2024189
Osteoarthritis (OA) is a significant contributor to pain and disability worldwide. Pain is the main complaint of OA patients attending the clinic and has a large impact on their quality of life and economic standards. However, existing treatments for OA-related pain have not been shown to achieve good relief. The main focus is on preventing and slowing the progression of OA so that the problem of OA pain can be resolved. Pain caused by OA is complex, with the nature, location, duration, and intensity of pain changing as the disease progresses. Previous research has highlighted the role of various forms of cell death, such as apoptosis and necrosis, in the progression of pain in OA. Emerging studies have identified additional forms of novel cell death, such as pyroptosis, ferroptosis, and necroptosis that are linked to pain in OA. Different types of cell death contribute to tissue damage in OA by impacting inflammatory responses, reactive oxygen species (ROS) production, and calcium ion levels, ultimately leading to the development of pain. Evidence suggests that targeting novel types of cell death could help alleviate pain in OA patients. This review delves into the complex mechanisms of OA pain, explores the relationship between different modes of novel cell death and pain, and proposes novel cell death as a viable strategy for the treatment of these conditions, with the goal of providing scientific references for the development of future OA pain treatments and drugs.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024093
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that knockdown of LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024154
The pathological proliferation and migration of vascular smooth muscle cells (VSMCs) are key processes during vascular neointimal hyperplasia (NIH) and restenosis. Phosphoenolpyruvate carboxy kinase 1 (PCK1) is closely related to a variety of malignant proliferative diseases. However, the role of PCK1 in VSMCs has rarely been investigated. This study aims to examine the role of PCK1 in the proliferation and migration of VSMCs and vascular NIH after injury. In vivo, extensive NIH and increased expression of PCK1 within the neointima are observed in injured arteries. Interestingly, the administration of adeno-associated virus-9 (AAV-9) carrying Pck1 short hairpin RNA (shPck1) significantly attenuates NIH and stenosis of the vascular lumen. In vitro, Pck1 small interfering RNA (siPck1)-induced PCK1 silencing inhibits VSMC proliferation and migration. Additionally, silencing of PCK1 leads to reduced expression of dynamin-related protein 1 (DRP1) and attenuated mitochondrial fission. Lentivirus-mediated DRP1 overexpression markedly reverses the inhibitory effects of PCK1 silencing on VSMC proliferation, migration, and mitochondrial fission. Finally, PCK1 inhibition attenuates the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Activation of STAT3 abolishes the suppressive effects of PCK1 silencing on DRP1 expression, mitochondrial fission, proliferation, and migration in VSMCs. In conclusion, PCK1 inhibition attenuates the mitochondrial fission, proliferation, and migration of VSMCs by inhibiting the STAT3/DRP1 axis, thereby suppressing vascular NIH and restenosis.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2023285
Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024144
Three-dimensional (3D) reconstruction serves as a crucial instrument for the analysis of biological structures. In particular, a comprehensive and accurate 3D ultrastructural examination of rat sperm is vital for understanding and diagnosing male fertility issues and the underlying causes of infertility. In this study, we utilize the automated tape-collecting ultramicrotome scanning electron microscopy (ATUM-SEM) imaging technique, which is a highly effective method for 3D cellular ultrastructural analysis. Our findings reveal that during spermiogenesis, the volume of the nucleus significantly decreases, shrinking to just 10% of its original size. The acrosomal vesicles derived from the Golgi apparatus converge and elongate along the spermatid nucleus. These vesicles then attach to the nucleus via a cap-like structure, thereby defining the head side of the spermatozoa. In the initial stages of spermiogenesis, the mitochondria in spermatids are distributed beneath the cell membrane. As the process progresses, these mitochondria gradually migrate to the sperm tail, where they form the mitochondrial sheath. This sheath plays a crucial role in providing the energy required for the movement of the sperm. In addition, we reconstruct the mRNA-stroring structure-chromatoid body in sperm cells, which are cloud-like or net-like structures in the cytoplasm. The precise and comprehensive nature of 3D ultrastructural examination allows for a deeper understanding of the morphological process of spermiogenesis, thereby contributing to our knowledge of male fertility and the causes of infertility. Our research has significantly advanced the understanding of the 3D ultrastructure of sperm more comprehensively than ever before.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261624
The bHLH transcription factor family in Forsythia suspensa was systematically identified and characterized using genomic data, yielding 170 members with complete HLH conserved domains distributed across 14 chromosomes. Protein lengths ranged from 67 to 885 amino acids, with relative molecular masses of 7,910.58 to 98,854.78 and theoretical isoelectric points of 4.71 to 10.44. Phylogenetic analysis classified these factors into 13 subfamilies, with subfamily III being the largest. Cis-acting element analysis revealed multiple light-, hormone-, and stress-responsive elements. Exogenous methyl jasmonate (MeJA) treatment of F. suspensa leaves followed by qRT-PCR within 48 h and correlation with phillygenin content identified FsbHLH26 and FsbHLH139 as likely key regulators of phillygenin biosynthesis and accumulation. These findings provide a foundation for elucidating the molecular mechanisms underlying phillygenin biosynthesis.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261610
Diosgenin (Dio) suffers from poor aqueous solubility and low oral bioavailability, limiting its clinical translation. This study developed diosgenin-rebaudioside A self-assembled nanomicelles (Dio-Reb A-SNM) using a combined drug-excipient strategy. Box-Behnken design-response surface methodology optimized the formulation: rebaudioside A to diosgenin ratio 12.32:1, diosgenin concentration 1.97 mg/mL, ultrasonic time 20.20 min. The optimized Dio-Reb A-SNM exhibited an encapsulation efficiency of 93.59±0.63%, drug loading of 5.65±0.07%, particle size of 25.66±1.76 nm, and zeta potential of -24.59±1.18 mV. Transmission electron microscopy revealed spherical morphology, and X-ray powder diffraction confirmed amorphization of diosgenin. The nanomicelles significantly enhanced saturated solubility across pH media and demonstrated sustained release (90.94% cumulative release at 18 h) fitting a Weibull model. Pharmacokinetic studies in SD rats showed that Dio-Reb A-SNM achieved a tmax of 2.06±0.29 h, t1/2 of 8.39±1.94 h, and increased Cmax and relative bioavailability by 3.59-fold and 6.82-fold, respectively, compared to free diosgenin. In a type 2 diabetes mellitus rat model, Dio-Reb A-SNM (30 mg/kg) significantly reduced blood glucose (P<0.01) and serum AST, ALT, urea nitrogen, and creatinine levels (P<0.01), with attenuated hepatic and renal pathological injury. These findings demonstrate that Dio-Reb A-SNM markedly improves oral absorption and hypoglycemic efficacy of diosgenin, providing a promising formulation strategy.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05051-z
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, driven by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear. Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD. Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal’s protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration. These effects are closely associated with the activation of SIRT1/FOXO3 signaling and the restoration of functional mitophagic flux. Our work highlights the SIRT1/FOXO3-mitophagy axis as a promising target for further investigation in the development of therapeutic strategies for IVDD.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-04954-1
Neuroinflammation is a central pathogenic driver of neurodegenerative diseases, including Alzheimer's disease (AD), for which therapeutic options remain limited. Mesenchymal stem cell (MSC) transplantation has emerged as a potential strategy to modulate neuroinflammation, but its efficacy is constrained by suboptimal anti-inflammatory potency. Prior work demonstrated that MSCs pretreated with tanshinone IIA (TIIA-MSC) exhibit superior anti-neuroinflammatory activity compared with naïve MSCs, yet the underlying mechanism remained undefined. This study integrated in vitro and in vivo experiments to evaluate TIIA-MSC in a triple-transgenic AD mouse model (3×Tg-AD) and to dissect mechanisms in a lipopolysaccharide (LPS)-induced BV2 microglial inflammation model. TIIA-MSC significantly improved cognitive function, increased brain glucose metabolism, promoted recovery of synaptic and mitochondrial structures, and alleviated neuroinflammatory responses in 3×Tg-AD mice. In vitro, TIIA-MSC more effectively inhibited microglial activation and proinflammatory factor release. Mechanistic analyses identified triggering receptor expressed on myeloid cells 2 (TREM2) as the key mediator: TREM2 knockdown significantly attenuated the anti-inflammatory effect of TIIA-MSC. Downstream, activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway promoted microglial transformation from a predominantly proinflammatory phenotype toward a neuroprotective, reparative state. These findings systematically reveal that TIIA-MSC regulate microglial phenotypic conversion through the TREM2/PI3K/Akt axis, providing mechanistic rationale and experimental basis for expanding MSC applications in neurodegenerative disease therapy.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026076
In Arabidopsis, the PPR proteins EMB1006, EMB1270, and EMB976 are all essential for the splicing of plastid clpP1 intron 2 (clpP1.2), although each also targets other distinct RNAs. The precise mechanism underlying their coordinated action in clpP1.2 splicing remains unclear. In this study, RNA electrophoretic mobility shift assays, guided by PPR code prediction, confirm that EMB1006 specifically binds to a sequence near the 3′ end of clpP1 exon 2. Additionally, immunoprecipitation coupled with mass spectrometry reveals that EMB1006 forms a complex with EMB1270, EMB976, and CFM2. Direct interactions between EMB1006 and EMB1270 or CFM2 are further supported by yeast two-hybrid (Y2H) and semi-in vivo pull-down assays. However, no direct interactions between EMB976 and EMB1006, CFM2 or EMB1270 are detected by Y2H. Based on these findings and previous evidence that EMB1270 binds to clpP1 intron 2 and interacts with CFM2, we propose a model in which EMB1006 and EMB1270 bind to distinct sites on clpP1 pre-mRNA. Together with CFM2 and possible indirect association with EMB976, they assemble into a protein-RNA complex that facilitates the splicing of clpP1.2 in chloroplasts.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025196
Human embryonic kidney (HEK) 293 cells are widely used for recombinant protein production because of their efficient posttranslational modification capabilities. However, their large-scale culture is often limited by metabolic stress and early apoptosis, leading to insufficient protein yields. In this study, we aim to increase protein expression through the coordinated modulation of metabolic and apoptotic pathways. Using CRISPR/Cas9 technology, we target and knockout the genes of ornithine decarboxylase antizyme 1 (OAZ1), which regulates polyamine metabolism, and caspase 8-associated protein 2 (CASP8AP2), an apoptosis-related protein. We successfully construct an OAZ1/CASP8AP2 double-knockout HEK293 cell line. Following transfection with the knockout vector and screening of single-cell clones, multiple levels of validation confirm the successful gene knockout. The results show that the double-knockout cells exhibit significantly reduced apoptosis rates. Furthermore, the production of recombinant secreted alkaline phosphatase (SEAP) and vitronectin (VN) increases by 2.1 folds and 2.9 folds, respectively, compared with those in wild-type cells. Metabolic profiling reveals that the cell cycle is arrested in the G1/G0 phase, accompanied by increased specific consumption and production rates of key metabolites. This study demonstrates that concurrent inhibition of apoptosis and optimization of metabolism effectively enhances recombinant protein production in HEK293 cells, suggesting a novel strategy for improving HEK293 cell-based expression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026025
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, represents an extremely aggressive malignancy. The induction of cuproptosis has developed into a favorable therapeutic direction for HCC, considering its strong association with HCC. Sanguinarine (San), a benzophenanthridine alkaloid derived from traditional herbs such as Chelidonium majus L., demonstrates broad-spectrum anticancer activities against various cancer cell types. However, the precise molecular mechanisms underlying its effects in the treatment of HCC remain largely undefined. This investigation seeks to examine the anti-HCC effects of San and to explore the mechanisms underlying these effects through the induction of cuproptosis. In vitro experiments demonstrate that San markedly inhibits the proliferation, movement, and epithelial-mesenchymal transition of HCC cells while enhancing their apoptosis. In vivo, San notably impedes tumor growth and upregulates the cuproptosis signature markers ferredoxin 1 (FDX1), oligomeric dihydrolipoamide S-acetyltransferase (DLAT), and heat shock protein 70 (HSP70) in HCC xenograft tumor models. Mechanistically, San induces proteotoxic stress and cuproptosis in HCC cells by increasing copper concentration, upregulating the expression of FDX1, lipoic acid synthetase (LIAS), HSP70, and lipoylated DLAT aggregation, and simultaneously reducing mitochondrial membrane potential and intracellular glutathione and pyruvate levels. Moreover, the combination of San with copper ionophores (Elesclomol-CuCl2) exhibits synergistic effects in promoting cuproptosis. FDX1 silencing markedly diminishes San-induced suppression of cell proliferation and FDX1 and HSP70 levels in HCC cells. Additionally, molecular docking analysis predicts that San exhibits the highest potential for binding with FDX1. Surface plasmon resonance experiments and cellular thermal shift assay confirm that San strongly interacts with FDX1 and markedly enhances the thermostability of FDX1. In conclusion, our findings indicate that San substantially inhibits the progression of HCC by targeting FDX1/LIAS/DLAT/HSP70 axis-dependent cuproptosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21207
BACKGROUND: Hypoxia preconditioning can increase extracellular vesicles, growth factors, anti-inflammatory and immunosuppressive factors in the parasecretory secretions of mesenchymal stem cells. Exosomes derived from human amniotic mesenchymal stem cells preconditioned with hypoxia are expected to play a better therapeutic role in tissue damage repair. OBJECTIVE: To observe the repair effect of exosomes from human amniotic mesenchymal stem cells preconditioned with hypoxia on radiation-induced submandibular gland epithelial cell damage. METHODS: The passage 3 human amniotic mesenchymal stem cells were divided into two groups: hypoxia and normoxia. They were pretreated with hypoxia (1% O2 by volume) and normoxia (20% O2 by volume) for 48 hours, respectively. Then, normoxic and hypoxic human amniotic mesenchymal stem cell exosomes were extracted from the culture supernatant of human amniotic mesenchymal stem cells by modified ultrahigh-speed centrifugation. The submandibular gland epithelial cells of SD newborn rats were divided into blank control group, radiation control group, normoxia-treated group, and hypoxia-treated group. The submandibular gland epithelial cells were treated with 5 Gy radiation to construct a radiation-induced injury model. The normoxia-treated and hypoxia-treated groups were co-cultured with normoxic or hypoxic exosomes for 3 days. CCK-8 assay was used to detect the proliferation activity of rat submandibular gland epithelial cells; ELISA was used to measure the content of α-amylase in the supernatant; RT-qPCR was used to detect the expression of aquaporin 5 mRNA. RESULTS AND CONCLUSION: The cell proliferation activity in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The cell proliferation activity in the normoxia-treated and hypoxia-treated groups on days 2 and 3 was significantly higher than that in the radiation control group (P < 0.05). The cell proliferation activity in the hypoxia-treated group on day 1 was higher than that in the normoxia-treated group, and showed an increasing trend on days 2 and 3, but there was no statistical difference compared with the normoxia-treated group (P > 0.05). The α-amylase content in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The α-amylase content in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). Compared with the normoxia-treated group, the α-amylase content in the hypoxia-treated group showed an increasing trend, but there was no statistical difference (P > 0.05). The expression of aquaporin 5 mRNA in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The expression of aquaporin 5 mRNA in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). The expression of aquaporin 5 mRNA in the hypoxia-treated group was slightly higher than that in the normoxia-treated group, but there was no statistical difference (P > 0.05). The results indicate that both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes have a repair effect on radiation-induced submandibular gland epithelial cell damage, but hypoxic exosomes have no obvious advantage.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21279
Objective: To systematically compare the acute effects of blood flow restriction combined with preconditioning (to induce post-activation performance enhancement) versus preconditioning alone or sitting, low-intensity preconditioning combined with blood flow restriction versus high-intensity preconditioning, and sitting combined with blood flow restriction versus sitting on sports performance using a multilevel meta-analysis. Methods: Following the PRISMA guidelines, Web of Science, PubMed, SPORTDiscus, and CNKI databases were systematically searched (from inception to May 24, 2025). Inclusion criteria: (1) healthy individuals who were at least physically active; (2) studies with at least one of the following four comparisons: preconditioning + blood flow restriction vs. preconditioning alone; preconditioning + blood flow restriction vs. sitting; low-intensity preconditioning + blood flow restriction vs. high-intensity preconditioning; sitting + blood flow restriction vs. sitting; (3) sports performance (e.g., jump, sprint, bench press throw) as the primary outcome; (4) randomized or non-randomized crossover/parallel designs; (5) published in peer-reviewed Chinese or English journals. Risk of bias was assessed using ROB-2, and evidence quality was evaluated with GRADE. Data were fitted using cluster robust variance estimation and a three-level mixed-effects model, with small-sample corrections. Subgroup analyses and meta-regression explored moderators and sources of heterogeneity. Results: Twelve studies (196 participants, 12 women, 184 men) were included. Main findings: (1) Preconditioning + blood flow restriction was more effective than preconditioning alone in enhancing sports performance (ES=0.21, 95%CI=0.01-0.40, GRADE=low), with the best effect at recovery times of 4-12 min and 50% arterial occlusion pressure (ES=1.49); (2) Preconditioning + blood flow restriction did not significantly differ from sitting (ES=0.52, 95%CI=-0.12-1.15, GRADE=very low), but preconditioning + 140 mmHg blood flow restriction was superior to preconditioning alone (ES=1.21, 95%CI=0.14-2.28); (3) Low-intensity preconditioning + blood flow restriction did not differ from high-intensity preconditioning (ES=-0.10, 95%CI=-0.84-0.64, GRADE=low); (4) Sitting + blood flow restriction did not significantly differ from sitting (ES=0.24, 95%CI=-0.03-0.52, GRADE=very low). Notably, the effects of the latter two comparisons significantly decreased with recovery time (β=-0.04, P < 0.01 and β=-0.04, P=0.02). Conclusion: Preconditioning combined with blood flow restriction is more effective than preconditioning alone in inducing post-activation performance enhancement, preliminarily suggesting the use of 50% arterial occlusion pressure and 4-12 min recovery time. However, preconditioning combined with blood flow restriction does not appear to be more effective than sitting, possibly due to insufficient number of included studies. Additionally, low-intensity preconditioning + blood flow restriction can achieve similar post-activation performance enhancement as high-intensity preconditioning, while the potential benefit of sitting + blood flow restriction on sports performance may diminish over time. Overall, it is preliminarily recommended to use low-intensity preconditioning (e.g., 30% one-repetition maximum squat or bodyweight training) combined with 50% arterial occlusion pressure or 140 mmHg blood flow restriction, with 4-12 min recovery before subsequent performance testing.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21370
BACKGROUND: In recent years, metabolic disorders have been confirmed to be closely related to the onset of osteoarthritis, but the causal relationship between plasma metabolites and osteoarthritis has not been systematically elucidated. OBJECTIVE: To explore the causal relationship between 1,400 plasma metabolites and 9 types of osteoarthritis using two-sample Mendelian randomization. METHODS: A genome-wide association study of 1,400 metabolites was used as the exposure. Nine types of arthritis, namely any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, hip osteoarthritis, spinal osteoarthritis, finger osteoarthritis, hand osteoarthritis, and thumb osteoarthritis, were set as the outcomes. Single nucleotide polymorphisms were used as instrumental variables, and sensitive single nucleotide polymorphisms were selected for Mendelian randomization analysis. The inverse variance weighted method was used as the main analysis approach. Meanwhile, four methods, namely MR-Egger, weighted median, simple mode, and weighted mode, were employed for cross-validation. MR-PRESSO, Cochran's Q test, and other methods were used for sensitivity and pleiotropy analyses. The false discovery rate method was used for further correction. RESULTS AND CONCLUSION: Mendelian randomization analysis showed that finger osteoarthritis, hand osteoarthritis, hip osteoarthritis, and spinal osteoarthritis had no results meeting FDR < 0.05. Any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, and thumb osteoarthritis were significantly causally associated with multiple metabolites. Metabolites such as glycine, serine, higenamine, and sulfate were closely related to multiple osteoarthritis types. Compared with some non-weight-bearing joint osteoarthritis (e.g., finger and hand osteoarthritis), plasma metabolites showed stronger sensitivity with weight-bearing joint osteoarthritis (e.g., knee and hip osteoarthritis). This study provides a theoretical basis for metabolic intervention strategies for osteoarthritis in the Chinese population and offers a methodological paradigm for mechanistic research on complex diseases in China.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21312
BACKGROUND: Although physcion has been shown to have protective effects against osteoporosis, the exact mechanism is not fully understood. OBJECTIVE: Through multidimensional analysis of the regulatory effect of physcion on the AKT signaling pathway, the molecular mechanism of its regulation on osteoclast induced differentiation and osteogenic function induced differentiation is revealed. METHODS: (1) RAW264.7 cells and C3H10T1/2 cells were cultured in vitro and subsequently exposed to 0, 10, 20, 30, 40, 50, and 60 µmol/L physcion, respectively. The cytotoxicity of physcion was detected by cell counting kit-8 assay. (2) RAW264.7 cells and C3H10T1/2 cells were treated with different concentrations (0, 20, 40 µmol/L) of physcion during osteoclast and osteoblast differentiation, respectively. Differentiation ability was assessed by qPCR, Western Blot, and alkaline phosphatase staining. (3) Network pharmacology was used to analyze the regulation of physcion on osteoclast differentiation and related signaling pathways, and molecular docking was performed for target proteins. (4) Western Blot was used to verify the phosphorylation level of AKT in the downstream target signaling pathway AKT axis regulated by physcion. RESULTS AND CONCLUSION: (1) At concentrations of 0-60 µmol/L, cell viability in all groups was greater than 90%, indicating no significant cytotoxicity. (2) Physcion significantly inhibited the expression of osteoclast differentiation-related genes, with Acp5, CTSK, DC-STAMP, and Nfatc1 showing downregulation, but had no significant effect on osteoblast differentiation-related genes COL1A1, Runx2, OSX expression or alkaline phosphatase staining intensity. (3) Network pharmacology and molecular docking suggested that physcion affects osteoclast differentiation and regulates the PI3K-AKT pathway, with a binding energy of -10.72 kJ/mol to AKT1, indicating strong binding activity. (4) During osteoclast differentiation, the p-AKT/AKT ratio in RAW264.7 cells increased (n=3, P=0.0063), while physcion decreased this ratio. These findings indicate that physcion inhibits osteoclast differentiation by regulating the AKT signaling pathway, thereby modulating bone homeostasis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21433
Background: Vestibular peripheral vertigo is characterized by a wide range of diseases, profound impact, and difficulty in prevention and treatment, posing a significant public health issue globally. Currently, randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for vestibular peripheral vertigo are complex and diverse, lacking standardized and systematic categorization, which constrains the quality of evidence-based evidence and clinical translation value. Objective: To systematically review RCTs of TCM for vestibular peripheral vertigo, analyze clinical research characteristics and outcome measures, to optimize the development of clinical guideline indicator sets and provide reference for future clinical trial design. Methods: PubMed, Web of Science, The Cochrane Library, EMbase, CNKI, VIP, Wanfang, and China Biology Medicine disc were searched from inception to April 18, 2025, to collect RCTs of TCM for vestibular peripheral vertigo. Two researchers independently conducted literature screening, data extraction, and quality assessment. Qualitative analysis was used to summarize clinical outcome measures and related trial design elements. Results and Conclusion: A total of 166 RCTs involving 14,718 patients were included, with 119 types of outcome measures. Outcome measures were categorized into 7 domains based on functional attributes: symptoms/signs, TCM syndromes, physical and chemical examinations, safety, long-term prognosis, quality of life, and others. Currently, the design of RCTs of TCM for vestibular peripheral vertigo has not formed a unified standard, with lack of standardization in TCM syndrome types and measurement tools, and numerous methodological quality issues. Clinical outcome measures exhibit prominent heterogeneity, imbalance between endpoint and surrogate indicators, unreasonable selection, neglect of economic indicators, and incomplete safety event and long-term prognosis evaluation systems. It is recommended that future researchers improve methodological quality, rationally design outcome measures, and align with the characteristics of TCM clinical trial efficacy evaluation, to promote the standardization of clinical guidelines and core indicator sets for vestibular peripheral vertigo, and provide more scientific and effective evidence-based medicine evidence for precise prevention and treatment.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21432
OBJECTIVE: Traditional meta-analyses have confirmed that exercise intervention can effectively improve chronic low back pain, but the evidence for which specific exercise method is more effective is still insufficient. Therefore, this article used a network meta-analysis to explore the differences in the effects of different exercise elements on improving chronic low back pain in adults. METHODS: Randomized controlled trials of exercise intervention for nonspecific chronic low back pain were searched in PubMed, Web of Science, Embase, Cochrane, CNKI, WanFang, and VIP databases. The trial group received any type of exercise intervention, while the control group received non-exercise interventions such as drug therapy and physical therapy. The search period was from the database inception to March 1, 2025. Boolean operators (AND/OR) were used to combine keywords for the search. Two reviewers independently completed literature screening, data extraction, and risk of bias assessment. Stata 17.0 software was used for network meta-analysis, and the surface under the cumulative ranking curve (SUCRA) was used to rank the effects of exercise dose variables. RESULTS: A total of 40 randomized controlled trials were included. Network meta-analysis showed that core stability training, mat exercise, traditional Chinese exercises, combined exercise, and other exercises were superior to the control group in improving chronic low back pain [SMD=-0.76, 95%CI(-1.39, -0.13), P < 0.05; SMD=-1.67, 95%CI(-2.48, -0.86), P < 0.05; SMD=-2.09, 95%CI(-3.37, -0.80), P < 0.05; SMD=-1.60, 95%CI(-2.71, -0.49), P < 0.05; SMD=-1.40, 95%CI(-2.40, -0.40), P < 0.05]. Suspension training was less effective than traditional Chinese exercises and mat exercise [SMD=1.50, 95%CI(0.05, 2.95), P < 0.05; SMD=1.09, 95%CI(0.11, 2.06), P < 0.05]. Traditional Chinese exercises were superior to core stability training [SMD=-1.32, 95%CI(-2.64, -0.01), P < 0.05]. Regarding exercise duration, sessions of 15-20 min and 30-40 min were superior to control [SMD=-1.96, 95%CI(-3.55, -0.36), P < 0.05; SMD=-1.44, 95%CI(-2.12, -0.76), P < 0.05]. Regarding frequency, 3 times/week and 6-7 times/week were superior to control [SMD=-1.03, 95%CI(-1.69, -0.37), P < 0.05; SMD=-1.83, 95%CI(-2.75, -0.91), P < 0.05], and 6-7 times/week was superior to 1-2 times/week [SMD=-1.30, 95%CI(-2.61, -0.06), P < 0.05]. Regarding duration of program, 4 weeks, 12-13 weeks, and ≥16 weeks were significantly superior to control [SMD=-0.81, 95%CI(-1.50, -0.12), P < 0.05; SMD=-1.63, 95%CI(-2.82, -0.43), P < 0.05; SMD=-2.14, 95%CI(-3.36, -0.92), P < 0.05], and ≥16 weeks was superior to 6 weeks [SMD=-1.55, 95%CI(-3.03, -0.07), P < 0.05]. SUCRA results showed that traditional Chinese exercises, 15-20 min per session, 6-7 times per week, and ≥16 weeks ranked highest in their respective categories. CONCLUSION: Traditional Chinese exercises (Tai Chi, Qigong, Wuqinxi, Baduanjin), 15-20 min per session, 6-7 times per week, and ≥16 weeks may be the most effective for relieving chronic low back pain in adults. However, due to the limited number of included studies, further research is needed to provide stronger evidence.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21407
BACKGROUND: The pathological process of intervertebral disc degeneration is accompanied by angiogenesis-lymphatic imbalance and changes in the immune microenvironment, both of which play important roles in intervertebral disc degeneration. OBJECTIVE: To systematically summarize the roles of angiogenesis-lymphatic imbalance-related cytokines in intervertebral disc degeneration. METHODS: The first author searched relevant literature published between January 2000 and April 2025 in the PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The Chinese search terms included "intervertebral disc degeneration, vascular-lymphatic imbalance, angiogenesis, vascular endothelial growth factor (VEGF), lymphatic vessel, Prox-1, immune microenvironment." A total of 65 articles were ultimately included for review. RESULTS AND CONCLUSION: During intervertebral disc degeneration, the vascular-lymphatic system and immune microenvironment play crucial roles in maintaining disc homeostasis. When disc degeneration occurs, angiogenesis and lymphatic disruption increase inflammatory factors within the disc, leading to enhanced degradation of the extracellular matrix. Concurrently, changes in the immune microenvironment, characterized by increased immune cell infiltration, elevated levels of pro-inflammatory cytokines and chemokines, and activation of local immune responses, modulate vascular and lymphatic vessels, ultimately reducing disc repair capacity and inducing chronic pain, thereby exacerbating the degree of disc degeneration.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21490
BACKGROUND: Traditional cell culture models have substantial limitations in accurately simulating the biological characteristics of tumors. Organoid technology, which retains key biological features of primary tumors, provides technical support for in-depth exploration of the pathogenesis of esophagogastric junction adenocarcinoma (EGJA) and for precision diagnosis and treatment research. OBJECTIVE: To construct a patient-derived organoid model of EGJA, evaluate its consistency with the biological characteristics of the primary tumor, and provide a standardized in vitro model for studying the pathogenesis and precision diagnosis and treatment of EGJA. METHODS: Surgical resection specimens from 50 patients with EGJA were collected for tissue dissociation, culture, and organoid model construction. Cell viability in organoid models was analyzed by fluorescence co-localization staining. Structural features of organoid models and primary tumor tissues were analyzed by hematoxylin-eosin staining. Mucin secretion phenotype in organoid models was detected by periodic acid-Schiff staining. Immunohistochemical staining was used to evaluate the consistency of organoid models with primary tumor histopathology. Chi-square test and univariate logistic regression were used to analyze the correlation between organoid model establishment success rate and patient clinicopathological features and tissue characteristics. RESULTS AND CONCLUSION: A patient-derived EGJA organoid model culture system was successfully established, with a primary culture success rate of 86.0% (43/50). Organoids exhibited typical three-dimensional structures, gradually developing from cell clusters into glandular-like three-dimensional solid spheres. After 7-10 days of primary culture, they could be stably passaged, and no significant phenotypic changes were observed after multiple passages. After cryopreservation and resuscitation, organoids still proliferated stably. Fluorescence co-localization staining showed that organoid models maintained high viability at different culture stages. Hematoxylin-eosin staining results showed that both organoid models and primary tumor tissues exhibited atypical glandular arrangement and high nuclear-to-cytoplasmic ratio. Periodic acid-Schiff staining showed positive mucin secretion. Immunohistochemical staining showed high consistency in the positive expression rates of Ki67, CEA, CK7, and Cadherin17 between organoid models and primary tumor tissues. Furthermore, chi-square test and logistic regression analysis showed that poorly differentiated tumor tissue (P=0.02), major pathological response to neoadjuvant chemotherapy (P=0.007), tumor tissue ex vivo time (P=0.006), and tumor mass (P=0.006) significantly affected the success rate of patient-derived EGJA organoid model establishment.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21619
BACKGROUND: Intraoperative blood loss in hip hemiarthroplasty is reduced with the supercapsular percutaneously assisted total hip approach compared with the posterolateral approach, but the difference in hidden blood loss between the two approaches and the effect of tranexamic acid on it has not been fully investigated. OBJECTIVE: To investigate whether the supercapsular percutaneously assisted total hip approach reduces perioperative hidden blood loss in hip hemiarthroplasty for unstable femoral neck fractures in advanced age compared with the posterolateral approach and to analyze the effect of combined local and intravenous tranexamic acid on it. METHODS: This study retrospectively analyzed a total of 200 elderly unstable femoral neck fracture patients who underwent hip hemiarthroplasty in the Department of Orthopedics, First Affiliated Hospital, Soochow University from January 1, 2020 to December 31, 2024. They were divided into four groups (n=50 per group) according to the surgical approach and whether tranexamic acid was used in the perioperative period: (1) posterolateral approach group; (2) posterolateral approach + tranexamic acid group (combined local and intravenous tranexamic acid); (3) supercapsular percutaneously assisted total hip approach group; (4) supercapsular percutaneously assisted total hip approach + tranexamic acid group (combined local and intravenous tranexamic acid). General data including age, sex, height, weight, and surgical side, as well as preoperative hemoglobin, hematocrit, prothrombin time, activated partial thromboplastin time, and fibrinogen were collected. Hemoglobin and hematocrit were measured on postoperative day 3, and total blood loss and hidden blood loss were calculated. RESULTS AND CONCLUSION: (1) There were no statistically significant differences in preoperative general data among the four groups. (2) The total blood loss and hidden blood loss on postoperative day 3 in the supercapsular percutaneously assisted total hip approach group were significantly lower than those in the posterolateral approach group (P < 0.05). (3) The total blood loss and hidden blood loss in the posterolateral approach + tranexamic acid group were significantly lower than those in the posterolateral approach group without tranexamic acid (P < 0.05). (4) The total blood loss and hidden blood loss in the supercapsular percutaneously assisted total hip approach + tranexamic acid group were significantly lower than those in the supercapsular percutaneously assisted total hip approach group without tranexamic acid (P < 0.05). (5) The incidence of lower extremity venous thrombosis was very low in all groups, with no statistically significant difference among groups. (6) These findings suggest that compared with the traditional posterolateral approach, the supercapsular percutaneously assisted total hip approach for hip hemiarthroplasty in elderly patients with unstable femoral neck fractures can reduce perioperative total blood loss and hidden blood loss; combined local and intravenous tranexamic acid can reduce perioperative blood loss in both traditional and supercapsular percutaneously assisted total hip approaches without increasing the risk of thrombosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21624
BACKGROUND: Lower extremity deep vein thrombosis is a catastrophic complication after lumbar spine fusion, and previous studies have shown that some patients, such as those with prosthetic arthroplasty and abdominal surgeries, suffer from a combination of preoperative anemia, which predisposes them to postoperative deep vein thrombosis of the lower extremities. However, whether preoperative anemia increases the risk of lower extremity deep vein thrombosis after lumbar spine fusion is unclear. OBJECTIVE: To investigate the correlation between preoperative anemia and deep vein thrombosis of the lower extremities in patients after lumbar fusion. METHODS: The clinical data of 1 178 patients who underwent lumbar spinal fusion treatment admitted to Third Affiliated Hospital of Anhui Medical University from January 2020 to December 2023 were retrospectively analyzed. According to whether or not the patients developed lower extremity deep vein thrombosis after the operation, the patients were divided into the deep vein thrombosis group (ultrasound report suggestive of lower extremity deep vein thrombosis) and the non-deep vein thrombosis group (ultrasound report suggestive of no lower extremity deep vein thrombosis). The incidence of anemia was compared between the two groups, and risk factors for lower extremity deep vein thrombosis in lumbar fusion patients were determined by univariate analysis and multivariate logistic regression analysis. RESULTS AND CONCLUSION: Among 1 178 patients, there were 43 cases (3.7%) in the deep vein thrombosis group and 1 135 cases (96.4%) in the non-deep vein thrombosis group. The incidence of preoperative anemia in the deep vein thrombosis group was 32.6%, significantly higher than that in the non-deep vein thrombosis group (10.9%, P < 0.05). Univariate analysis showed significant differences between the two groups in preoperative hemoglobin (P < 0.001), preoperative red blood cell count (P=0.028), D-dimer positivity (P=0.029), hypertension (P=0.019), number of fused segments (P=0.023), anemia (P < 0.001), and blood transfusion (P=0.006) (P < 0.05). Multivariate analysis showed that preoperative anemia (OR=4.221, 95%CI: 1.198-14.802, P=0.025) and D-dimer positivity (OR=2.023, 95%CI: 1.065-3.844, P=0.031) were risk factors for lower extremity deep vein thrombosis after lumbar fusion. These findings suggest that the incidence of preoperative anemia is relatively high in patients undergoing elective lumbar fusion, and preoperative anemia is an independent risk factor for deep vein thrombosis after lumbar fusion. It is recommended that preoperative anemia should be actively managed and corrected before elective lumbar fusion to reduce the risk of lower extremity deep vein thrombosis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21585
BACKGROUND: Previous studies have demonstrated neuroprotective potential of microRNA-23a-3p in traumatic brain injury. However, direct evidence is still lacking regarding whether this protective effect stems from its precise regulation of the M1/M2 polarization balance of microglia. OBJECTIVE: To clarify the expression changes of microRNA-23a-3p in mouse brain tissue after traumatic brain injury and to explore the specific mechanism by which it affects neurological function through regulating microglial polarization. METHODS: Eighty C57BL/6J mice were randomly assigned to four groups: a sham operation group, a traumatic brain injury group, a traumatic brain injury + agomir-NC group, and a traumatic brain injury + agomir-MicroRNA-23a-3p group. The traumatic brain injury model was established using the cortical impact method. The sham group did not receive cortical impact. The intervention groups received intracerebroventricular injection of agomir-NC or agomir-MicroRNA-23a-3p after modeling. Six mice from the sham and traumatic brain injury groups were analyzed at 1, 3, 7, and 14 days post-injury, and six mice from the other two groups were analyzed at 14 days post-injury. Neurological deficits were assessed using the modified neurological severity score (mNSS). Hematoxylin-eosin staining and Nissl staining were used to observe pathological changes in brain tissue and neurons. qRT-PCR and western blot were used to detect the expression levels of MicroRNA-23a-3p, M1 markers (CD16, CD86), M2 markers (CD206, arginase-1), and inflammatory cytokines (tumor necrosis factor-α and interleukin-10). Immunohistochemistry was used to evaluate microglial M1/M2 polarization and the aggregation of F4/80-positive cells in the injured area. RESULTS AND CONCLUSION: Compared with the sham group, the expression of MicroRNA-23a-3p in the traumatic brain injury group showed a "V"-shaped curve, with downregulation in the early phase and upregulation starting at 7 days post-injury. Upregulation of MicroRNA-23a-3p reduced the mNSS score in traumatic brain injury mice. Morphological results showed that upregulation of MicroRNA-23a-3p alleviated brain edema and neuronal damage. Molecular biology results showed that upregulation of MicroRNA-23a-3p promoted microglial polarization from M1 to M2 phenotype. These findings indicate that MicroRNA-23a-3p can promote neurological function recovery after traumatic brain injury in mice by regulating microglial polarization.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026036
Forkhead box protein M1 (FOXM1) is a key transcription factor that regulates cell cycle progression and is frequently overexpressed in human cancers, driving tumor proliferation and therapy resistance. FOXM1 recognizes the canonical forkhead response element (FKH motif, RYAAAYA) through its conserved DNA-binding domain (DBD). Here, we report the high-resolution crystal structure of the FOXM1-DBD in complex with a double-stranded DNA substrate containing two FKH motifs. The structure reveals that FOXM1-DBD adopts the canonical winged-helix fold, with the third α-helix (α3) inserted into the DNA major groove to mediate sequence-specific recognition. Within this helix, Asn283, Arg286, and His287 form an essential triad that engages DNA bases through specific hydrogen bonds and hydrophobic interactions. Using structure-guided mutagenesis of key DNA-interacting residues combined with biophysical validation by isothermal titration calorimetry (ITC) and DNA binding assessment via electrophoretic mobility shift assay (EMSA), we confirm the functional importance of these residues and uncover position-dependent tolerance to base substitutions within the FKH motif. Furthermore, we demonstrate that FOXM1 overexpression promotes cell proliferation and upregulates the transcription of target genes in a DBD-dependent manner. Our findings provide a structural basis for understanding the DNA recognition mechanism of FOXM1 and offer mechanistic insights into how FOXM1 selectively binds to its genomic targets to regulate transcription.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025042
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with late-stage 5-year survival rates below 50%. Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) drive progression, yet the molecular mediators of CAF-tumor crosstalk are incompletely defined. This study identifies platelet-derived growth factor C (PDGFC) as a critical CAF-secreted factor that promotes epithelial-mesenchymal transition (EMT) and immunosuppression in LUAD. Analysis of patient specimens revealed elevated PDGFC expression in CAFs relative to nontumor tissue fibroblasts (NFs), and high PDGFC levels correlated with poor prognosis. Mechanistically, CAF-derived PDGFC activates the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in cancer cells, inducing EMT and matrix metalloproteinase 2 (MMP2) expression. PDGFC also stimulates PDGFRA expression in both tumor cells and fibroblasts, establishing a reciprocal positive feedback loop that accelerates fibrotic TME remodeling and malignant progression. Immunologically, PDGFC promotes infiltration and polarization of immunosuppressive cell populations, including CD4+ Treg cells, M2 macrophages, and N2 neutrophils, while restraining immunocompetent NK cells. Immunoinhibitors TGFB1, CSF1R, PD-L1, PD-L2, KDR, IL10RB, and HAVCR2 may synergize with PDGFC in modulating immunosuppression. These findings position PDGFC as a diagnostic indicator and potential immunotherapy target for LUAD, offering a novel TME-targeted therapeutic strategy.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731785313317742
Background: Heart failure with recovered ejection fraction (HFrecEF) is a distinct phenotype with unclear clinical characteristics and prognosis. Methods: We prospectively enrolled 1,234 patients with heart failure and reduced ejection fraction (HFrEF) from January 2015 to December 2018. After optimal medical therapy, 312 patients (25.3%) achieved recovery of left ventricular ejection fraction (LVEF) to ≥50% and were classified as HFrecEF. Clinical characteristics, medication use, and outcomes were compared with those who remained HFrEF. The primary outcome was a composite of all-cause death and heart failure hospitalization. Results: Compared with HFrEF patients, HFrecEF patients were younger, more likely to be female, had a higher prevalence of hypertension and atrial fibrillation, and had a shorter duration of heart failure. They had lower baseline levels of NT-proBNP and smaller left ventricular dimensions. Over a median follow-up of 3.2 years, HFrecEF patients had a significantly lower risk of the primary outcome (adjusted HR 0.45, 95% CI 0.32-0.63, p<0.001). However, 23.4% of HFrecEF patients experienced deterioration of LVEF during follow-up, and these patients had a worse prognosis compared with those who maintained recovery. Independent predictors of LVEF deterioration included ischemic etiology, diabetes, and non-adherence to guideline-directed medical therapy. Conclusions: HFrecEF is associated with a better prognosis than HFrEF, but a substantial proportion of patients may experience LVEF deterioration. Continued optimization of medical therapy and close monitoring are essential for this population.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025109
Infection-induced cytokine storm remains a principal driver of organ failure in sepsis, with MAPK signaling as a validated but undrugged target. We previously demonstrated that the gut microbiota-derived monosaccharide rhamnose enhances macrophage phagocytosis; here we interrogate its immunomodulatory capacity in endotoxemia. In an LPS-induced murine endotoxic model, plasma rhamnose levels increased significantly. Rhamnose alone did not perturb inflammatory cytokine homeostasis or cause organ damage, yet it robustly attenuated endotoxin-induced systemic inflammation and organ injury. Mechanistically, in macrophages, rhamnose binds the V39, D40, and T101 residues of carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1), promoting CEACAM1–galectin 9 (LGALS9) interaction, which elevates dual-specificity protein phosphatase 1 (DUSP1) protein levels. DUSP1 dephosphorylates p38, suppressing LPS-triggered proinflammatory factor expression. These findings define a rhamnose–CEACAM1/LGALS9–p38 axis that suppresses endotoxemia-associated inflammation, positioning rhamnose as a candidate anti-inflammatory agent for infection-induced organ damage.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025089
Cuproptosis, a copper-dependent cell death modality driven by acylated protein aggregation and mitochondrial proteotoxic stress, intersects with inflammatory signaling. Hexokinase domain-containing protein 1 (HKDC1), the fifth hexokinase, regulates mitochondrial function, yet its role in cuproptosis and LPS-induced macrophage inflammation remains undefined. Using THP-1-derived macrophages, we assessed plasticity via CCK8 viability and phagocytosis assays, quantified inflammatory factors and cuproptosis-related proteins by western blot and RT-qPCR, and mapped HKDC1 expression/localization through ChIP-qPCR and immunofluorescence. LPS elevated inflammatory cytokines, suppressed cuproptosis, activated glycolysis, and induced HKDC1 via TLR4. HKDC1 knockdown reversed these effects, inhibiting glycolysis and triggering cuproptosis. Mechanistically, LPS promoted Yin Yang 1 (YY1) binding to the HKDC1 promoter, driving transcription. HKDC1 interacted with HSCB and FDX1, increasing intracellular copper and cuproptosis. In vivo, HKDC1 knockdown alleviated acute sepsis by activating copper-dependent cell death. These findings establish HKDC1 as a central node linking LPS, glycolysis, and cuproptosis, proposing a cuproptosis-dependent anti-inflammatory strategy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025073
HECTD3, a HECT-domain E3 ubiquitin ligase, is overexpressed in multiple malignancies and has been implicated in apoptosis resistance and platinum chemoresistance. Prior work from our group detected HECTD3 protein overexpression in 42/79 (53%) breast carcinomas versus 6/42 (14%) normal or adjacent normal breast tissues, yet the prognostic significance of this alteration in breast cancer remained undefined. Here we performed immunohistochemical staining for HECTD3 on two independent cohorts: 320 human breast cancer samples from the First Affiliated Hospital of Kunming Medical University (cohort 1) and a tissue microarray of 227 breast cancer samples plus 39 adjacent normal breast tissues from the Second Xiangya Hospital of Central South University (cohort 2). Staining was interpreted by two pathologists using a validated anti-HECTD3 antibody. Survival associations were assessed using the KMplot.com database. High HECTD3 expression was significantly associated with prolonged overall survival (P = 0.02), distant-metastasis-free survival (P = 0.031), and relapse-free survival (P < 0.0001). These findings establish that HECTD3 protein is frequently overexpressed in human breast cancers and that positive HECTD3 staining correlates with favorable clinical outcomes, identifying HECTD3 as a candidate good prognostic biomarker in breast cancer patients.