Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04274-w
Background Alternative splicing not only expands the genetic encoding of genes but also determines cellular activities. This study aimed to elucidate the regulation mechanism and biological functions of lincRNA-ASAO in the process of odontogenesis-related genes alternative splicing mediated odontogenic differentiation of hDPSCs. Methods RACE, RNA-seq, FISH and bioinformatics techniques were used to identify novel lincRNA-ASAO. ALP staining, alizarin red staining, qRT-PCR and western blot were used to identify the role of lincRNA-ASAO in regulating the odontoblast differentiation of hDPSCs. The binding protein PTBP1 of lincRNA-ASAO was screened by RNA-Pull-down, protein profiling and bioinformatics. The target gene ALPL of lincRNA-ASAO/PTBP1 was identified by RNA-seq, bioinformatics technology and DNA agarose gel electrophoresis. FISH, IF, PAR-CLIP and bioinformatics techniques were used to determine the roles of lincRNA-ASAO, PTBP1 and ALPL pre-mRNA in the odontoblast differentiation of hDPSCs. Results We identified a novel lincRNA-ASAO that could promote the odontogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). And, the interaction between lincRNA-ASAO and alternative splicing factor PTBP1 promoted the odontoblast differentiation of hDPSCs. In addition, lincRNA-ASAO forms duplexes with ALPL pre-mRNA, targeting PTBP1 to exonic splicing silencer (ESS) of ALPL and regulating exon 2 skipping. Notably, lincRNA-ASAO/PTBP1 regulated ALPL production to increase the type 2 splice variant, which promoted the odontoblast differentiation of hDPSCs. Conclusions We have identified the novel lincRNA-ASAO, which can promote the odontoblast differentiation of hDPSCs. The mechanism study found that lincRNA-ASAO/PTBP1 mediated the exon 2 skipping of ALPL pre-mRNA, resulting in the type 2 splice variant of ALPL. Our results enrich the understanding of lncRNAs and alternative splicing in regulating the odontoblast differentiation of hDPSCs, and provide clues to improve the clinical therapeutic potential of hDPSCs for dental pulp restoration.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025253
Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive subtype of renal cell carcinoma and is characterized by poor prognosis and high molecular heterogeneity. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer, yet the functional role of SNHG11 in KIRC remains unclear. In this study, we perform integrated multiomics analysis using data from the TCGA and ICGC cohorts and reveal that SNHG11, a methylation-associated lncRNA, is significantly correlated with poor clinical outcomes. In vitro and in vivo assays demonstrate that SNHG11 promotes tumor proliferation and progression. Mechanistically, SNHG11 enhances oxidative phosphorylation, as evidenced by increased ATP production, disrupted mitochondrial membrane potential, and altered NAD+/NADH ratios. Furthermore, SNHG11 expression is associated with somatic mutation patterns, particularly those involving BAP1 and PBRM1, indicating potential crosstalk between epigenetic regulation and genetic alterations. These findings reveal that SNHG11 is a novel biomarker in KIRC and a potential therapeutic target.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025233
This is a corrigendum to the article 'Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness by activating the TGF-β/Smad signaling pathway in breast cancer cells' published in Acta Biochim Biophys Sin 54: 1587–1598. The authors identified inaccuracies in the preparation of several figures (Figure 2D, 4A, and 5A) and have replaced them with corrected versions. The errors are strictly confined to figure presentation and do not impact the underlying data, statistical analysis, or main conclusions. The authors apologize for the oversight.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025121
Carfilzomib (Cfz) is a second-generation proteasome inhibitor approved for the treatment of relapsed/refractory multiple myeloma (RRMM). Previous studies have shown that Cfz is associated with a higher incidence of severe adverse cardiac effects than bortezomib (Btz); however, the underlying mechanisms remain to be elucidated. The aim of this study is to identify key regulators of cardiotoxicity induced by Cfz and to investigate the mechanisms by which these factors exert their effects. We establish a mouse model of cardiac toxicity induced by Cfz and confirm the phenotype through cardiac functional analysis, morphology assessment, myocardial fibrosis, and apoptosis analysis. We subsequently perform RNA sequencing to identify differentially expressed genes (DEGs) and further validate their functions and mechanisms. We find that Cfz induces myocardial hypertrophy and myocardial injury, along with the suppression of SENP1 expression in mouse heart tissues and in vitro cultured neonatal rat cardiomyocytes. Suppression of SENP1 exacerbates Cfz-induced injury and remodeling in cardiomyocytes by directly binding to and deconjugating the SUMO1-mediated SUMOylation of the RNA helicase DDX17. This process leads to a reduction in K-48 ubiquitin-linked polyubiquitination and degradation of DDX17, resulting in increased expressions of anti-apoptotic genes and maintenance of mitochondrial homeostasis. Therefore, the overexpression of SENP1 using AAV vectors alleviates Cfz-induced cardiotoxicity in mice. In summary, our findings reveal a previously unknown role of the SENP1-DDX17 axis in protecting against cardiotoxicity induced by Cfz, providing a potential foundation for developing therapeutic strategies to mitigate cardiac side effects in the clinical management of MM patients.
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•2024•DOI: 10.3724/abbs.2024141
Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024042
Lotus seed skin extract is rich in flavonoids, making it a promising candidate for developing health products. In a previous study, we found that proanthocyanidins from lotus seed skin, particularly proanthocyanidin B1 (PB1), can indirectly activate the Nrf2 signaling pathway, exerting an antioxidant effect. In this study, we isolate proanthocyanidins from lotus seed skin (PLS) using ethanol extraction and RP-HPLC identification, and investigate its effects on glycolipid metabolism both in vivo and in vitro. Our results demonstrate that PLS reduces body weight in high-fat diet (HFD) mice by decreasing feed efficiency. PLS also normalizes serum glucose, insulin secretion, glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance (IPGTT). Furthermore, PLS significantly improves blood lipid parameters and inhibits the expressions of six proinflammatory factors, including IL-1α, IL-1β, IL-3, IL-6, IFN-γ and TNF-α in HFD mice. Additionally, analysis of fresh liver tissues reveals that PLS and PB1 induce the expressions of antioxidant proteins such as HO-1 and NQO1 by activating the p38-Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway. In conclusion, proanthocyanidins from lotus seed skin regulate glycolipid metabolism disorders by targeting the p38/Nrf2/NF-κB signaling pathway. Our study offers a new approach for the high-value comprehensive utilization of lotus seed skin by-products and precise dietary intervention for metabolic syndrome.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025095
Alzheimer’s disease (AD) is the most common neurodegenerative disease that usually begins with short-term memory loss, gradually progresses to cognitive dysfunction and causes loss of body function and eventual death. Mutations in the APP gene encoding the Aβ precursor protein (APP) are known to cause early-onset AD and suggest that Aβ is a major factor in AD development. Enzyme complexes, such as α-, β- and γ-secretases, catalyze various cleavage pathways to produce a variety of Aβ isoforms of different lengths. These Aβ peptides have proven toxic to the brain and accumulate in AD to form cerebral plaques. The main isoform of Aβ present in these plaques is the 42 amino acid variant known as Aβ42. A previous study revealed that changes in the stiffness of the extracellular matrix (ECM) can induce remodeling of the cytoskeleton of neurons in the brain tissues of AD patients, leading to changes in the morphology and function of neurons. ECM stiffness is unique to each specific tissue, and resident cells have developed to function optimally in microenvironments with specific ECMs. Brain tissues are reported to have a Young’s modulus of elasticity between 0.1 and 16 kPa. In patients with AD, a decrease in the elasticity of brain tissues was detected. Interestingly, the ECM is known to play an important role in cytoskeleton remodeling and neuronal function, and a stiff ECM has been reported to promote actin polymerization and stress fiber formation, whereas a soft ECM triggers actin depolymerization. However, it remains uncertain whether alterations in ECM stiffness in the AD brain contribute to Aβ-induced toxicity, particularly considering that Aβ is recognized to cause neuronal toxicity by disrupting the actin cytoskeleton, which leads to subsequent synaptic and dendritic abnormities. As such, the present study aimed to investigate the effects of substrate stiffness on Aβ-induced toxicity to the neuronal network in cultured neurons. Hippocampal neurons cultured on soft and stiff substrates were assessed for cell viability by MTT assay. When the neuronal cultures were exposed to 1 μM Aβ42 for 48 h, there was a significant decrease in the viability of the cells cultured on the stiff substrates, but there was no significant effect on the viability of the neuronal cultured on the soft substrates. In addition, the influence of Aβ42 on the number of synapses within the cultured neuronal network was analyzed using confocal immunofluorescence imaging. This analysis revealed that Aβ42 exposure induced a decrease in synaptic formation in cultured neurons, which was dependent on substrate stiffness. To evaluate the effect of substrate stiffness on Aβ42-induced toxicity to synaptic transmission in the cultured neuronal network, spontaneous Ca2+ oscillations were examined in neurons cultured on substrates with different stiffness treated with Aβ42. The percentage of neurons with spontaneous Ca2+ oscillations was significantly greater in neurons cultured on stiff substrates than in those cultured on soft substrates. After Aβ42 exposure, the percentage of neurons with spontaneous Ca2+ oscillations was significantly decreased in neurons cultured on the stiff substrates. Exposure to Aβ42 only slightly influenced the percentage of spontaneous Ca2+ oscillations in neurons cultured on the soft substrate. The amplitude and frequency of spontaneous Ca2+ oscillations were significantly greater in neurons cultured on the stiff substrates than in those cultured on the soft substrates. After exposure to Aβ42, the amplitude and frequency of spontaneous Ca2+ oscillations were significantly reduced in neurons cultured on stiff substrates. However, exposure to Aβ42 had only a weak influence on the amplitude and frequency of spontaneous Ca2+ oscillations in neurons cultured on soft substrates. To further investigate the effects of substrate stiffness on synapse function following exposure to Aβ42, spontaneous postsynaptic currents were recorded in DIV14-16 neurons cultured on stiff and soft substrates. The percentage of neurons with spontaneous postsynaptic currents was considerably greater in neurons cultured on the stiff substrates than in those cultured on soft substrates.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025067
Adrenocortical carcinoma (ACC) is a rare epithelial tumor originating from adrenal cortical cells, notable for its high degree of malignancy and poor prognosis. Owing to heterogeneity, patient outcomes vary significantly. Current biomarkers for ACC risk stratification have notable limitations. However, with the advancement of multi-omics sequencing technology, we can utilize multi-omics data to explore the heterogeneity of ACC, thereby identifying novel biomarkers. In this study, we establish multicenter transcriptomics and ATAC-seq data from the TCGA and GEO databases to perform weighted gene coexpression network analysis (WGCNA) clustering and conduct comprehensive analyses of various ACC samples. These findings are integrated with univariate Cox regression, receiver operating characteristic (ROC) curve analysis, and survival analysis to identify potential biomarkers. We establish FSCN1 as an independent risk factor associated with poor ACC prognosis. ATAC-seq data demonstrate higher chromatin accessibility of FSCN1 in ACC patients with progressive disease. Immunohistochemical analysis confirms the expression of FSCN1 at the protein level, while functional cell assays reveal its role in promoting tumor invasion and proliferation. Functional enrichment analyses highlight the biological characteristics of FSCN1, and estimation of TME-infiltrating cells suggests that FSCN1 expression contributes to poor prognosis by inhibiting CD8+ T-cell infiltration within the ACC microenvironment. Finally, multi-omics analyses elucidate the role of FSCN1 at the mutation level. Taken together, our findings highlight FSCN1 as a promising novel biomarker and potential therapeutic target, underscoring its value in guiding the strategic management of ACC.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024070
Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 μg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of β-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of β-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing β-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024227
Fibroblast growth factor 21 (FGF21) plays a pivotal role in regulating metabolic processes and energy homeostasis, making it a promising therapeutic avenue for various obesity-related conditions. However, its therapeutic efficacy faces challenges due to its suboptimal pharmacokinetics and bioactivity. To overcome these limitations, we adapt a strategy in which key amino acid residues responsible for enhanced activity are pinpointed through sequence alignment and comparative analysis to develop long-acting FGF21 analogs. The mutant FGF21 analogs are fused with the Fc fragment. Here, we report the design, identification, and characterization of two distinct Fc-fused FGF21 analogs, Fc-FGF21(P119R) and Fc-FGF21(H125R), with significantly augmented potency. These findings hold promise for clinical applications, offering potential interventions for obesity-related metabolic disorders.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261502
Methicillin-resistant Staphylococcus aureus (MRSA) accounts for over 30% of clinical S. aureus isolates globally, with bacteremia mortality reaching 27.3%—approximately threefold that of methicillin-sensitive infections. Existing antibiotics face cross-resistance across β-lactams, macrolides, quinolones, and sulfonamides. This study isolated five compounds from the ethyl acetate fraction of Callicarpa nudiflora dried leaf ethanol extract via silica gel, Sephadex LH-20, and ODS column chromatography. Structures were elucidated by IR, HR-ESI-MS, 1H-NMR, 13C-NMR, HSQC, HMBC, and COSY. Compound 1, a new monoterpene named callinuene A, is (Z)-2-methyl-6-methyleneocta-2,7-dien-1-yl (E)-3-(4-hydroxyphenyl)acrylate. Compounds 2–5 were identified as monasuslunin, (1S,5R,9R)-10,10-dimethyl-2,6-dimethylenebicyclo[7.2.0]undecan-5-ol, 7-epi-eudesm-4(15)-ene-1β,6β-diol, and sclareolide, respectively; compounds 3–5 are first isolates within this species. Minimum inhibitory concentrations (MICs) were determined by nutrient broth dilution. Compound 1 exhibited MICs of 8 μg/mL against S. aureus ATCC29213 and MRSA T144, while MICs against E. coli ATCC25922 and multidrug-resistant E. coli B2 exceeded 128 μg/mL. Compounds 2–5 showed no meaningful activity (MIC ≥ 64 μg/mL). Oxacillin MICs were <0.25, 16, 32, and 32 μg/mL for the same strains; meropenem MICs were <0.25, 2, <0.25, and <0.25 μg/mL. Compound 1 demonstrates selective anti-staphylococcal activity, warranting further development as a lead scaffold against MRSA.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261614
Aging-related sarcopenia remains a clinical challenge due to limited effective interventions. This study systematically evaluated the therapeutic potential of the iridoid fraction from Morinda officinalis and elucidated its mechanism via the PI3K/Akt/mTOR pathway. Using monotropein and deacetylasperulosidic acid as markers, extraction was optimized with 60% ethanol under heated reflux, yielding the highest iridoid content. Purification employed H103 macroporous resin with water as eluent, achieving maximal recovery. In vitro, the fraction significantly ameliorated D-galactose-induced C2C12 myotube atrophy (P < 0.001) and promoted myotube differentiation (P < 0.05, 0.01, 0.001), as evidenced by MYHC expression. In vivo, D-galactose-accelerated aging mice treated with the fraction exhibited increased limb grip strength and hindlimb muscle mass-to-body weight ratio (P < 0.05, 0.01, 0.001), along with expanded cross-sectional area of tibialis anterior and gastrocnemius muscles (P < 0.01, 0.001). Transcriptomic and network pharmacology analyses implicated the PI3K/Akt pathway. Western blotting and qRT-PCR confirmed upregulation of key proteins and genes (PIK3CA, AKT1, mTOR) in the pathway (P < 0.05, 0.01, 0.001), while the PI3K inhibitor LY294002 reversed these effects (P < 0.05). These findings demonstrate that the iridoid fraction from M. officinalis mitigates aging-related sarcopenia through PI3K/Akt/mTOR signaling, providing a promising candidate for clinical translation.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025253
Kidney renal clear cell carcinoma (KIRC) is the most common and aggressive subtype of renal cell carcinoma and is characterized by poor prognosis and high molecular heterogeneity. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer, yet the functional role of SNHG11 in KIRC remains unclear. In this study, we perform integrated multiomics analysis using data from the TCGA and ICGC cohorts and reveal that SNHG11, a methylation-associated lncRNA, is significantly correlated with poor clinical outcomes. In vitro and in vivo assays demonstrate that SNHG11 promotes tumor proliferation and progression. Mechanistically, SNHG11 enhances oxidative phosphorylation, as evidenced by increased ATP production, disrupted mitochondrial membrane potential, and altered NAD+/NADH ratios. Furthermore, SNHG11 expression is associated with somatic mutation patterns, particularly those involving BAP1 and PBRM1, indicating potential crosstalk between epigenetic regulation and genetic alterations. These findings reveal that SNHG11 is a novel biomarker in KIRC and a potential therapeutic target.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21289
BACKGROUND: The pathogenesis of ulcerative colitis is highly complex, necessitating the development of models that more closely mimic human physiological and pathological responses to study the mechanisms underlying its onset and progression. OBJECTIVE: To establish a mouse ulcerative colitis organoid model. METHODS: Colon organoids of C57BL/6J mice were extracted, cultured and passaged in vitro. Colon organoids from mice after three generations of passage were taken and incubated in lipopolysaccharide at varying concentrations [0 (control), 150, 175, 200, 225, 250, 275, 300, 325, and 350 μg/mL] to induce inflammation for 24 hours. The morphology of mouse colon organoids was observed under a microscope, and changes in proliferation viability were assessed using the cell counting kit-8 assay. After 24 hours of incubation with 0, 225, 250, 275 μg/mL lipopolysaccharide, the levels of tumor necrosis factor α, interleukin-6, interleukin-9, and interleukin-10 were measured by ELISA. After 24 hours of incubation with 0 and 275 μg/mL lipopolysaccharide, the expression of occludin and zonula occludens-1 was detected by immunofluorescence staining, and the mRNA expression of tumor necrosis factor α, interleukin-6, interleukin-9, occludin, and zonula occludens-1 was detected by q-PCR. RESULTS AND CONCLUSION: (1) Under the microscope, colon organoids in the 150-275 μg/mL lipopolysaccharide group showed varying degrees of swelling, while those in the 300-350 μg/mL lipopolysaccharide group had inhibited growth and swelling. CCK-8 assay showed that 150-350 μg/mL lipopolysaccharide reduced the proliferation viability of mouse colon organoids, with 225-350 μg/mL having a more pronounced effect. Based on cell morphology and proliferation viability results, 225, 250, and 275 μg/mL lipopolysaccharide were selected for ELISA. (2) Compared with the control group, the levels of interleukin-6 and tumor necrosis factor α were increased in the 225, 250, and 275 μg/mL lipopolysaccharide groups (P < 0.05), and the level of interleukin-9 was increased in the 275 μg/mL lipopolysaccharide group (P < 0.05). (3) Immunofluorescence staining showed that compared with the control group, the expression of occludin and zonula occludens-1 was decreased in the 275 μg/mL lipopolysaccharide group. q-PCR detection showed that compared with the control group, the mRNA expression of interleukin-6 and tumor necrosis factor α was increased (P < 0.05), occludin mRNA expression was decreased (P < 0.05), and there was no significant difference in the expression of interleukin-9 and zonula occludens-1 (P > 0.05). (4) These results indicate that an in vitro mouse ulcerative colitis model based on organoids was successfully constructed, providing a powerful tool for studying the mechanisms of ulcerative colitis and screening effective drugs.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21335
BACKGROUND: The T cell immunosuppressive activity of mesenchymal stromal cells offers new hope for the treatment of autoimmune diseases. Amimatoside injection, a drug of human umbilical cord mesenchymal stromal cells, has been approved for the treatment of acute graft-versus-host disease (GVHD) primarily affecting the digestive tract, after steroid therapy failure, in patients aged 14 years and older. Therefore, further exploration of the T cell immunosuppressive potential of mesenchymal stromal cells can lay a foundation for the treatment of autoimmune diseases.
OBJECTIVE: To investigate the effect of programmed death ligand 1 (PD-L1) gene overexpression on the inhibition of CD4+ T cell proliferation by human umbilical cord mesenchymal stromal cells (hUC-MSCs).
METHODS: (1) hUC-MSCs were cultured in vitro to passages 0, 1, 2, and 3, and the percentage of PD-L1-positive cells was detected by flow cytometry. (2) hUC-MSCs were divided into experimental group and negative control group. The experimental group was transduced with lentivirus-mediated PD-L1 gene, while the negative control group was transduced with lentivirus carrying empty plasmid vector. Transfection efficiency was assessed by flow cytometry, real-time quantitative PCR, and western blot. (3) CD4+ T cells were enriched from healthy human peripheral blood using magnetic beads, labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE), and co-cultured with hUC-MSCs from the experimental and negative control groups at a ratio of 5:1. The proportion of CFSE-dim CD4+ T cells was detected by flow cytometry. (4) RNA sequencing was performed on hUC-MSCs from both groups, and single-cell RNA sequencing was performed on the experimental group. Subgroups were identified based on function, and bioinformatics analysis was used to depict heatmaps of marker genes, enriched signaling pathways, and gene regulatory networks for each subgroup.
RESULTS AND CONCLUSION: (1) The percentage of PD-L1-positive cells in hUC-MSCs gradually decreased with increasing passage number. (2) hUC-MSCs stably overexpressing PD-L1 were successfully constructed, with significantly increased PD-L1 expression in the experimental group. (3) Transcriptome sequencing data suggested that PD-L1-overexpressing hUC-MSCs promoted the upregulation of genes related to immune effector regulatory pathways. (4) Co-culture of CD4+ T cells with hUC-MSCs showed a significant decrease in the proportion of CD4+ T cells in the experimental group. (5) Based on single-cell RNA sequencing results, PD-L1-overexpressing hUC-MSCs could be divided into three functional subgroups with heterogeneity; PD-L1 gene expression was higher in subgroup 1, and the significantly high expression of histone methyltransferase SETDB1 might be closely related to enhanced T cell immunosuppressive function. These findings indicate that PD-L1 gene overexpression can significantly enhance the T cell immunosuppressive capacity of hUC-MSCs. Single-cell RNA sequencing can effectively classify PD-L1 gene-modified hUC-MSCs based on their functional characteristics, providing theoretical support for improving the clinical efficacy of hUC-MSCs.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21419
BACKGROUND: Experiments have confirmed that ferroptosis is closely associated with a variety of orthopedic diseases. However, the specific mechanisms by which the regulation of ferroptosis leads to orthopedic diseases remain unclear. Current evidence suggests that signaling pathways may be an important approach for regulating the occurrence of ferroptosis. OBJECTIVE: To summarize the relevant signaling pathways involved in the regulation of ferroptosis in orthopedic diseases (osteoarthritis, spinal cord injury, osteoporosis, intervertebral disc degeneration, rheumatoid arthritis, osteosarcoma, steroid-induced osteonecrosis of the femoral head), to describe the key regulators of the ferroptosis pathway in orthopedic diseases through the modulation of the conduction of signaling pathways, and to conduct an in-depth study on the regulatory mechanisms of ferroptosis in orthopedic diseases and provide a theoretical basis for the prevention and treatment of such diseases. METHODS: Databases including PubMed, Elsevier, Web of Science, and CNKI were searched for relevant literatures on ferroptosis and related orthopedic diseases from the establishment of these databases up to February 2025. The search terms were "ferroptosis, osteoarthritis, osteoporosis, spinal cord injury, intervertebral disc degeneration, osteosarcomas, rheumatoid arthritis, steroid-induced osteonecrosis of the femoral head". A total of 138 articles were included for review. RESULTS AND CONCLUSION: (1) Under the regulation of multiple signaling pathways, the accumulation of intracellular iron ions, reactive oxygen species, and other substances can be induced, causing ferroptosis in osteoblasts, chondrocytes, osteosarcoma cells, etc., leading to changes in the microenvironment, thereby promoting or inhibiting the occurrence of related orthopedic diseases. (2) Studies have confirmed that signaling pathway-regulated ferroptosis is of great significance in the pathogenesis of orthopedic diseases. (3) However, the interaction mechanisms among signaling pathways, ferroptosis, and orthopedic diseases are still in the preliminary stage, and further research is needed to provide more strategies for the treatment of orthopedic diseases.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21614
BACKGROUND: Meniscus injury, as a significant contributing factor to knee joint degeneration, can accelerate the progression of osteoarthritis through anterior horn tears that alter joint stress distribution. Existing studies primarily focus on biomechanical changes in normal bone conditions, while the regulatory role of different bone conditions on the injury mechanism remains unclear. OBJECTIVE: To investigate the effect of medial meniscus anterior horn transverse tears on the biomechanical differences of knee joints with varying bone conditions. METHODS: Imaging data of the lower limb from a healthy adult were used to construct a normal knee joint model in Mimics 2017. The model was further optimized and assembled using Geomagic Studio 2017 and SolidWorks 2017, and a medial meniscus anterior horn transverse tear model was established. Material properties were assigned in Ansys Workbench 2017, and three finite element models were created to simulate normal bone, reduced bone mass, and osteoporosis conditions. The models were validated using anterior drawer and axial loading tests. With the femur constrained and the distal tibia fixed, a 1000 N axial compressive load was applied to calculate stress peaks and strain distributions. RESULTS AND CONCLUSION: (1) Under static standing conditions, both normal and injured medial meniscus models showed significantly higher joint stress loads in reduced bone mass and osteoporosis groups compared to normal bone mass group. (2) The medial meniscus anterior horn transverse tear model exhibited a progressive increase in stress loads on femoral cartilage and both menisci compared to the normal model, while stress on tibial cartilage surfaces decreased with bone mass reduction. In the meniscus injury model, stress concentrated at the tear edges. (3) Subchondral bone regions showed elevated stress levels under reduced bone mass conditions, especially after medial meniscus injury, with significantly increased strain distribution range and equivalent stress peaks (P < 0.05). (4) These findings suggest that medial meniscus anterior horn transverse tears under reduced bone density exacerbate joint contact area reduction and local stress concentration, potentially leading to increased local strain in tibial subchondral bone, indicating an interactive biomechanical effect between bone degeneration and meniscus injury. This provides a reference for meniscus repair strategies considering bone quality differences.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21530
BACKGROUND: The clinical efficacy of Yanggan Roujin Decoction in delaying intervertebral disc degeneration is significant; however, its underlying mechanism remains unclear. OBJECTIVE: To validate the potential mechanisms by which Yanggan Roujin Decoction delays intervertebral disc degeneration using network pharmacology techniques and animal experiments. METHODS: (1) The effective components of Yanggan Roujin Decoction and their action targets were screened using the Traditional Chinese Medicine Systems Pharmacology Database and High-Throughput Experiment- and Reference-Guided Database of Traditional Chinese Medicine. Gene sets related to intervertebral disc degeneration were obtained from the Genecard, CTD, and DisGeNet databases. A protein-protein interaction network was constructed using the STRING database, and core targets were identified. The drug-component-target-disease network was constructed using Cytoscape 3.9.1 software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the Ouyi Biological Cloud Platform to obtain potential therapeutic mechanisms. (2) A rat model of intervertebral disc degeneration was established by percutaneous puncture of the annulus fibrosus. Different doses of Yanggan Roujin Decoction and diclofenac sodium were administered. Histopathological staining was used to assess structural changes in intervertebral disc tissue before and after intervention. Western blot and quantitative real-time PCR were used to detect the expression of core targets and related pathways. RESULTS AND CONCLUSION: Network pharmacology analysis identified 187 active components of Yanggan Roujin Decoction, mainly including β-sitosterol, sitosterol, stigmasterol, quercetin, and kaempferol. There were 298 potential targets for treating intervertebral disc degeneration, mainly including tumor protein p53, transcription factor c-Jun, interleukin-6, tumor necrosis factor α, protein kinase B, and insulin. These targets were mainly involved in enzyme binding, nitric oxide synthase regulatory activity, and signaling pathways such as mitogen-activated protein kinase, hypoxia-inducible factor 1, tumor necrosis factor, and interleukin-17. Animal experiments showed that Yanggan Roujin Decoction effectively alleviated pathological structural changes in intervertebral disc tissue caused by annulus fibrosus puncture. Compared with the blank control group, the model group showed increased protein and mRNA expression of tumor protein p53, transcription factor c-Jun, interleukin-6, and tumor necrosis factor α (P < 0.01), while protein kinase B and insulin protein and mRNA expression decreased (P < 0.01). Meanwhile, the expression of representative genes in the mitogen-activated protein kinase signaling pathway (P38, extracellular regulated protein kinase) and tumor necrosis factor signaling pathway (interleukin-1β, tumor necrosis factor α) increased, while the expression of representative genes in the hypoxia-inducible factor 1 signaling pathway (hypoxia-inducible factor 1α, vascular endothelial growth factor A) decreased. After intervention with different doses of Yanggan Roujin Decoction, the protein and mRNA expression of tumor protein p53, transcription factor c-Jun, interleukin-6, and tumor necrosis factor α decreased (P < 0.01), while protein kinase B and insulin protein and mRNA expression increased (P < 0.01). Simultaneously, the expression of representative genes in the mitogen-activated protein kinase signaling pathway (P38, extracellular regulated protein kinase) and tumor necrosis factor signaling pathway (interleukin-1β, tumor necrosis factor α) decreased, while the expression of representative genes in the hypoxia-inducible factor 1 signaling pathway (hypoxia-inducible factor 1α, vascular endothelial growth factor A) increased. After diclofenac sodium intervention, the protein and mRNA expression of interleukin-6 and tumor necrosis factor α decreased (P < 0.01), and the protein and mRNA expression of representative genes in the tumor necrosis factor signaling pathway (interleukin-1β, tumor necrosis factor α) decreased, but there were no significant differences in other indicators. These results indicate that Yanggan Roujin Decoction can effectively delay the progression of intervertebral disc degeneration, and the mechanism may be related to the regulation of tumor protein p53, transcription factor c-Jun, interleukin-6, tumor necrosis factor α, protein kinase B, insulin target genes, inhibition of mitogen-activated protein kinase and tumor necrosis factor signaling pathways, and activation of hypoxia-inducible factor 1 signaling pathway.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21571
BACKGROUND: Numerous studies have confirmed that quercetin can inhibit the release of inflammatory factors and reduce local inflammatory responses in wounds, creating favorable conditions for wound healing. However, quercetin has poor water solubility and low bioavailability, which limits its application in wound treatment. OBJECTIVE: To investigate the antibacterial properties of quercetin-silver nanoparticle/methacrylated hyaluronic acid composite hydrogels. METHODS: Quercetin-silver nanoparticles (QuAgNPs) were synthesized by hydrothermal reduction method. QuAgNPs were loaded into methacrylated hyaluronic acid (HAMA) hydrogel precursor solution at different mass concentrations (1, 5, 10, 20, 40, 60, 80 μg/mL) to prepare composite hydrogels, denoted as 1, 5, 10, 20, 40, 60, 80 μg/mL QuAgNPs/HAMA hydrogels, while pure HAMA hydrogels were also prepared. Staphylococcus aureus was co-cultured with 1, 5, 10, 20, 40, 60, 80 μg/mL QuAgNPs/HAMA hydrogels, and antibacterial properties were detected by inhibition zone experiment. In vitro drug release properties of 60 and 80 μg/mL QuAgNPs/HAMA hydrogels were tested. Based on the results of the inhibition zone experiment, appropriate QuAgNPs/HAMA hydrogels were selected for subsequent experiments. The microstructure of HAMA hydrogel and 60 μg/mL QuAgNPs/HAMA hydrogel was observed under scanning electron microscope. Staphylococcus aureus (or Escherichia coli) were co-cultured with QuAgNPs, HAMA hydrogel, and 60 μg/mL QuAgNPs/HAMA hydrogel, with bacteria cultured alone as blank control, and antibacterial rates were detected by spread plate antibacterial experiment. Human umbilical vein endothelial cells were co-cultured with QuAgNPs, HAMA hydrogel extract, and 60 μg/mL QuAgNPs/HAMA hydrogel extract, with cells cultured alone as blank control, and cell viability was detected by live/dead cell staining. RESULTS AND CONCLUSION: The inhibition zone experiment showed that the antibacterial properties of 60 and 80 μg/mL QuAgNPs/HAMA hydrogels were stronger than those of 1, 5, 10, 20, 40 μg/mL QuAgNPs/HAMA hydrogels, and there was no difference between 60 and 80 μg/mL QuAgNPs/HAMA hydrogels. Both 60 and 80 μg/mL QuAgNPs/HAMA hydrogels had good in vitro drug release properties. Therefore, 60 μg/mL QuAgNPs/HAMA hydrogel was selected for subsequent experiments. Scanning electron microscopy showed that HAMA hydrogel had a loose porous structure, and approximately spherical QuAgNPs particles were scattered on the surface of 60 μg/mL QuAgNPs/HAMA hydrogel. Spread plate antibacterial experiment showed that QuAgNPs and 60 μg/mL QuAgNPs/HAMA hydrogel had significant inhibitory effects on Staphylococcus aureus and Escherichia coli. Live/dead cell staining showed that QuAgNPs, HAMA hydrogel, and 60 μg/mL QuAgNPs/HAMA hydrogel did not affect cell viability and had good cytocompatibility. These results indicate that QuAgNPs/HAMA composite hydrogel has good antibacterial properties.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21577
BACKGROUND: Recent studies have shown that Chlorella possesses potential value in treating rheumatoid arthritis. The pathological progression of rheumatoid arthritis is closely associated with an imbalance in oxidative stress, abnormal macrophage polarization, aggressive activation of fibroblast-like synoviocytes, and disturbances in the vascular endothelial system. However, the optimization of extraction processes for peptides derived from Chlorella and their regulatory effects on key pathological links of rheumatoid arthritis remain to be systematically validated. OBJECTIVE: To optimize the extraction process of antioxidant peptides from Chlorella, clarify their antioxidant activity and biosafety, and explore their regulatory effects on pathological phenotypes of rheumatoid arthritis-related cells (RAW 264.7 mouse monocyte macrophage leukemia cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells), providing experimental evidence for the treatment of rheumatoid arthritis with Chlorella peptides. METHODS: (1) Chlorella peptide extract was prepared by bromelain enzymatic hydrolysis combined with phosphomolybdic acid precipitation. Using peptide yield as the evaluation index, the extraction process parameters were optimized by single-factor experiments, including solid-liquid ratio, enzymatic hydrolysis time, and reaction system pH. (2) The peptide content was determined by BCA method, antioxidant capacity was detected by ABTS method, and biosafety of peptides on RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells was evaluated by CCK-8 method. (3) An inflammatory model of RAW 264.7 cells induced by lipopolysaccharide was established. The effects of peptides on intracellular reactive oxygen species levels and M1/M2 polarization phenotypes were detected by DCFH-DA staining, flow cytometry, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (4) An activation model of fibroblast-like synoviocytes induced by tumor necrosis factor-alpha was established. The effects of peptides on migration, proliferation, invasion, and related gene expression of fibroblast-like synoviocytes were detected by wound healing assay, EdU proliferation assay, Transwell invasion assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. (5) An abnormal activation model of human umbilical vein endothelial cells induced by vascular endothelial growth factor A was established. The effects of peptides on migration, tube formation, and expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes were detected by wound healing assay, Transwell assay, tube formation assay, and real-time fluorescence quantitative reverse transcription polymerase chain reaction. RESULTS AND CONCLUSION: (1) The optimal extraction process for Chlorella peptides was solid-liquid ratio of 2:1 (g:100 mL), enzymatic hydrolysis time of 60 minutes, and reaction system pH of 6.5, yielding the highest peptide yield. (2) Chlorella peptides exhibited concentration-dependent antioxidant activity and showed no obvious toxicity to RAW 264.7 cells, fibroblast-like synoviocytes, and human umbilical vein endothelial cells in the concentration range of 1-10 μg/mL, indicating good biocompatibility. (3) Chlorella peptides dose-dependently inhibited lipopolysaccharide-induced reactive oxygen species generation in RAW 264.7 cells, downregulated M1 pro-inflammatory genes such as interleukin-1 beta and tumor necrosis factor-alpha, upregulated M2 anti-inflammatory genes such as interleukin-10 and arginase 1, and promoted macrophage polarization from M1 to M2 phenotype. (4) Chlorella peptides significantly inhibited tumor necrosis factor-alpha-induced migration, proliferation, and invasion of fibroblast-like synoviocytes, and downregulated the expression of interleukin-6, matrix metalloproteinase 13, tumor necrosis factor receptor superfamily member 11A, and C-X-C motif chemokine ligand 12. (5) Chlorella peptides effectively inhibited vascular endothelial growth factor A-induced migration and tube formation of human umbilical vein endothelial cells, and reduced the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A genes. These results indicate that Chlorella peptides regulate multiple pathological links of rheumatoid arthritis through anti-oxidative stress, regulation of macrophage polarization, inhibition of aggressive phenotype of fibroblast-like synoviocytes, and improvement of vascular endothelial disorders, suggesting potential therapeutic value for rheumatoid arthritis.
Chinese Journal of Pathophysiology•2026•DOI: 10.3969/j.issn.1000-4718.2026.04.010
AIM: Acute hypoxia can induce transient contraction of coronary arteries, leading to myocardial ischemia and even cardiac dysfunction. However, the precise regulatory mechanisms remain unclear. In this study, we applied various interventions to isolated porcine coronary arteries by modulating cytoplasmic calcium concentrations mediated by calcium channels on the plasma membrane and sarcoplasmic reticulum, aiming to investigate the relationship between hypoxic contraction and intracellular calcium levels as well as calcium sensitization effects. METHODS: Isolated rings of the porcine left anterior descending coronary artery served as the experimental model. Based on distinct intervention targets, four core experimental groups were established. The specific grouping, sample size (n) for each group, and treatments were as follows: (1) nitric oxide (NO)-soluble guanylyl cyclase (sGC) pathway and energy metabolism intervention groups including control (n=5), nitric oxide synthase inhibitor nitro-L-arginine (NLA, 10^-4 mol/L; n=4 to 5), soluble guanylyl cyclase (sGC) antagonist 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3×10^-5 mol/L; n=5), endothelium-denuded (n=5), normal glucose incubation (n=3), and glucose-free incubation (n=3) groups; (2) calcium source intervention groups including normal calcium control (n=4), calcium-free incubation with 5×10^-3 mol/L ethylene glycol tetraacetic acid (EGTA; n=4), L-type calcium channel antagonist nifedipine (10^-6 mol/L; n=5 to 7), non-selective cation channel inhibitor NiCl2 (5×10^-5 mol/L; n=5 to 7), sarcoplasmic reticulum Ca²⁺-ATPase inhibitor thapsigargin (2×10^-6 mol/L; n=5 to 7), and inositol trisphosphate (IP3) receptor antagonist 2-aminoethoxydiphenyl borate (2-APB, 10^-4 mol/L; n=5 to 7) groups; (3) myosin light chain kinase (MLCK) pathway intervention groups including control (n=4) and MLCK-specific inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7, 10^-5 mol/L; n=6) groups; (4) myosin light chain phosphatase (MLCP) activity and endothelium-dependence intervention groups including endothelium-intact (n=4) and mechanically endothelium-denuded (n=6) groups. All arterial rings were pre-contracted with either U46619 (3×10^-7 mol/L) or KCl (6×10^-2 mol/L) and then subjected to 10 minutes of hypoxia (95% N2+5% CO2). Changes in vascular tension were continuously monitored and recorded using a multi-channel physiological signal acquisition system. Furthermore, combined with Western blotting, the phosphorylation level of myosin light chain (MLC) and the activity of MLCP were determined; the phosphorylation levels of MLC and MLCP were also compared between endothelium-intact and endothelium-denuded coronary arteries under hypoxic conditions. RESULTS: (1) Hypoxic constriction of porcine coronary arteries is dependent on the activation of endothelium-derived nitric oxide (NO) and sGC in vascular smooth muscle cells. (2) Hypoxic contraction in porcine coronary arteries is independent of extracellular Ca²⁺ influx. (3) Hypoxic contraction in porcine coronary arteries does not rely on intracellular Ca²⁺ release from the sarcoplasmic reticulum. (4) Hypoxic contraction in porcine coronary arteries leads to inhibition of myosin light chain phosphatase activity, suggesting increased calcium sensitization in coronary artery smooth muscle. CONCLUSION: The mechanism underlying acute hypoxia-induced vasoconstriction exhibits distinct characteristics: it does not rely on extracellular calcium influx mediated by plasma membrane calcium channels, nor is it associated with intracellular calcium mobilization from sarcoplasmic reticulum stores. Instead, it is mediated by a significant enhancement in calcium sensitivity regulated by myosin light chain phosphatase, a process referred to as calcium sensitization.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025095
Alzheimer's disease (AD) is characterized by progressive cognitive decline, with amyloid-beta (Aβ) peptides, particularly Aβ42, playing a central role in neurotoxicity. The extracellular matrix (ECM) stiffness of brain tissue, typically 0.1–16 kPa, is altered in AD patients, but its contribution to Aβ42-induced toxicity remains unclear. This study investigated the effects of substrate stiffness on Aβ42 toxicity in cultured hippocampal neurons. Neurons were cultured on soft and stiff polyacrylamide (PA) gel substrates and exposed to 1 μM Aβ42 for 48 h. Cell viability, synaptic formation, spontaneous Ca2+ oscillations, and spontaneous excitatory/inhibitory postsynaptic currents (sEPSCs/sIPSCs) were assessed. Results showed that Aβ42 significantly reduced viability on stiff substrates but not on soft substrates. Synaptic formation decreased in a stiffness-dependent manner. The percentage of neurons with spontaneous Ca2+ oscillations was significantly greater on stiff substrates than on soft substrates following Aβ42 exposure. Electrophysiological recordings revealed that Aβ42 altered the percentage of neurons with sEPSCs and sIPSCs, as well as their amplitudes and frequencies, with differential effects based on substrate stiffness. These findings demonstrate that ECM stiffness modulates Aβ42-induced neurotoxicity, with stiff substrates exacerbating toxic effects on neuronal network activity. This suggests that ECM stiffness is a critical factor in AD pathogenesis and may inform therapeutic strategies targeting the mechanical microenvironment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025233
This corrigendum addresses inaccuracies in three figure panels from the original article (Acta Biochim Biophys Sin 54: 1587–1598, doi: 10.3724/abbs.2022150). The authors identified that Figure 2D was mislabeled during preparation, Figure 4A contained an incorrect image due to a processing error, and Figure 5A was mistakenly replaced during final compilation. Corrected versions of these panels are provided. The authors confirm that these errors are confined to figure presentation and do not affect the underlying data, statistical analyses, or the main conclusions of the study. The original research demonstrated that caveolin-1 (CAV-1)-deficient fibroblasts promote migration, invasion, and stemness in breast cancer cells (BCCs) via activation of the TGF-β/Smad signaling pathway. Key experimental methods included Western blot for CAV-1 expression, scratch wound healing assays for migration, Transwell assays for migration and invasion, immunofluorescence and ELISA for TGF-β1 detection, and Western blot for EMT/stemness markers. Statistical significance was set at P < 0.05. This corrigendum ensures the accuracy of the scientific record and maintains the integrity of the reported findings.