Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261607
This study addresses the pharmacodynamic material basis of Houttuynia cordata volatile oil by integrating supramolecular "imprinting template" theory with matching frequency, total statistical moment, and factor rotation methods, coupled to in vitro antitumor activity. Fifty-eight batches (S1–S58) from different origins were fingerprinted by GC-MS. The matching frequency method reduced the imprinting template to 34 structural "material units" (A1–A34). Integration significantly decreased average peak count and information entropy (P < 0.01), while total zero-, first-, and second-order moments and information content remained unchanged. Factor rotation extracted eight common factors; comprehensive scores ranked S16 and S54 highest and S24 and S27 lowest. CCK-8 assays against human lung adenocarcinoma A549 cells yielded IC50 values from 73.6 to 269.9 nL/mL. Comprehensive scores negatively correlated with IC50 (r = −0.739, P < 0.01). High-contribution units A34, A31, and A7 were preliminarily identified as a potential pharmacodynamic component group. The model demonstrates utility for trend-level quality evaluation but does not provide one-to-one prediction of single-batch efficacy. Limitations include restriction to volatile constituents, single-cell-line validation, and lack of independent isolation and enrichment for the flagged units. The protocol offers a transferable statistical framework for linking chromatographic fingerprints to bioactivity in complex botanical oils.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025148
Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21338
BACKGROUND: Exosomes derived from mesenchymal stem cells play an important role in regulating apoptosis, promoting cell regeneration, and improving the wound microenvironment, making them a hot research topic in the treatment of diabetic foot ulcers. OBJECTIVE: To explore the clinical application value of exosomes derived from human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers. METHODS: A retrospective analysis was conducted on the data from 72 patients with diabetic foot ulcers treated between May 2022 and April 2025. Thirty-six patients received treatment with exosomes derived from human umbilical cord mesenchymal stem cells (observation group), and 36 patients were managed with vacuum-assisted closure therapy (control group). Ulcer healing rate, incidence of adverse events, serum inflammatory markers, growth factor levels, total wound healing time, and ulcer recurrence rate during follow-up were compared between the two groups after 2 weeks of treatment. RESULTS AND CONCLUSION: (1) After 2 weeks of treatment, the ulcer healing rate in the observation group (48.03±6.12)% was significantly higher than that in the control group (30.13±6.38)%, with a significant difference (P < 0.05). (2) Ulcers healed in both groups, with healing time in the observation group (30.42±2.30) d significantly shorter than that in the control group (43.94±3.46) d (P < 0.05). (3) The incidence of adverse events during treatment was 13.89% in the control group and 19.44% in the observation group, with no significant difference (P > 0.05). (4) Serum levels of interleukin-6, C-reactive protein, and procalcitonin decreased significantly in both groups, with a greater decrease in the observation group (P < 0.01); serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor increased significantly in both groups, with a greater increase in the observation group (P < 0.01). (5) After ulcer healing, the observation group was followed for an average of 9.4 months, with 5 cases of ulcer recurrence; the control group was followed for an average of 9.8 months, with 10 cases of recurrence. The recurrence rate in the observation group was significantly lower than that in the control group (13.9% vs. 27.8%, P < 0.05). These results indicate that compared with vacuum-assisted closure therapy, application of exosomes derived from human umbilical cord mesenchymal stem cells for repairing diabetic foot ulcers can effectively inhibit inflammation, promote ulcer healing, and reduce recurrence rate without increasing the risk of related adverse events, demonstrating both efficacy and safety.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21520
BACKGROUND: 10-Hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, antioxidant, and immunomodulatory effects, but its role in regulating bone metabolism remains unclear. OBJECTIVE: To investigate the regulatory effects and potential mechanisms of 10-HDA in bone remodeling. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) were cultured with different concentrations of 10-HDA (0, 0.5, 1, 2, 4 mmol/L); cytoskeletal staining, live/dead staining, and CCK-8 assay were used to assess cell morphology, viability, and proliferation. For osteogenic differentiation, BMSCs were cultured with 10-HDA (0, 0.5, 1, 2 mmol/L) and osteogenic induction; alkaline phosphatase (ALP) and alizarin red staining were performed, and osteogenic-related protein expression was analyzed by western blot and immunofluorescence. Mouse bone marrow mononuclear cells were induced to differentiate into macrophages and cultured in osteoclast differentiation medium with different concentrations of 10-HDA (0, 0.5, 1, 2 mmol/L); tartrate-resistant acid phosphatase (TRAP) and F-actin staining were used to detect osteoclast formation. BMSCs were serum-starved for 6 h and then cultured normally, divided into control, 10-HDA, 10-HDA+AS1842856 (FOXO1 inhibitor), and 10-HDA+EX-527 (SIRT1 inhibitor) groups; 10-HDA concentration was 0.5 mmol/L. Western blot and immunofluorescence were used to analyze SIRT1/FOXO1 pathway activation and expression of autophagy- and osteogenesis-related proteins. BMSCs were divided into control, H2O2, and H2O2+10-HDA groups; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; after osteogenic induction, ALP and alizarin red staining were performed. BMSCs were divided into five groups: control, H2O2, H2O2+10-HDA, H2O2+10-HDA+AS1842856, and H2O2+10-HDA+EX-527; 10-HDA concentration was 0.5 mmol/L; after H2O2 treatment for 24 h, corresponding drug interventions were applied; western blot was used to detect SIRT1/FOXO1 signaling pathway and antioxidant-related protein expression; TUNEL and β-galactosidase staining were used to assess apoptosis and senescence. RESULTS AND CONCLUSION: Cytoskeletal staining, live/dead staining, and CCK-8 assay showed that 0.5, 1, 2 mmol/L 10-HDA promoted proliferation of rat BMSCs; these three concentrations were selected for subsequent experiments. ALP, alizarin red staining, western blot, and immunofluorescence analysis showed that 0.5 mmol/L 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs and increased osteogenic-related protein expression. TRAP and F-actin staining showed that 0.5 mmol/L 10-HDA significantly inhibited osteoclast formation. Western blot and immunofluorescence showed that 10-HDA activated the SIRT1/FOXO1 signaling pathway, promoted FOXO1 deacetylation and nuclear translocation, and upregulated autophagy-related proteins and antioxidant enzymes. ALP and alizarin red staining showed that under oxidative stress, 10-HDA promoted osteogenic differentiation and mineralization of rat BMSCs. Western blot showed that under oxidative stress, 10-HDA enhanced the antioxidant capacity of rat BMSCs by activating the SIRT1/FOXO1 signaling pathway. TUNEL and β-galactosidase staining showed that under oxidative stress, 10-HDA reduced apoptosis and senescence of rat BMSCs via activation of the SIRT1/FOXO1 signaling pathway. These findings indicate that 10-HDA enhances autophagy and antioxidant capacity through regulation of the SIRT1/FOXO1 signaling pathway, thereby promoting osteogenic differentiation.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025221
Hypertension is commonly accompanied by endothelial dysfunction, characterized by an imbalance between vasodilatation and constriction, increased levels of the proinflammatory factors interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), and decreased nitric oxide (NO) bioavailability. Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage. GYY4137 restores sirtuin 6 (SIRT6) expression, suppresses inflammation, and improves vasodilatory function. Furthermore, endothelial-specific cystathionine-γ-lyase (CSE)-deficient mice exhibit inflammation and endothelial dysfunction in blood vessels, which is reversed by H₂S supplementation. Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway.