Nan Fang Yi Ke Da Xue Xue Bao = Journal Of Southern Medical University[JOURNAL]
Sun
200 papers
[Astragaloside IV alleviates D-GAL-induced endothelial cell senescence by promoting mitochondrial autophagy inhibiting the PINK1/Parkin pathway].
Yi M, Luo Y, Wu L … +4 more , Wu Z, Jiang C, Chen S, Ke X
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311084 · Full text
OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GA...
OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS: AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
[High YEATS2 expression promotes epithelial-mesenchymal transition in gastric cancer cells by activating the Wnt/β-catenin signaling pathway].
Jiang X, Huang Q, Xu Y … +5 more , Wang S, Zhang X, Wang L, Wang Y, Zuo L
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311083 · Full text
OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed usi...
OBJECTIVES: To investigate YEATS2 expression in gastric cancer (GC), its prognostic value, and its regulatory role in epithelial-mesenchymal transition (EMT) of GC cells. METHODS: YEATS2 expression in GC was analyzed using publicly available databases. Paired GC and adjacent tissues were collected from 100 patients undergoing radical surgery for immunohistochemical detection of YEATS2 expression, and its correlations with the patients' clinicopathological parameters and Ki67 expression were analyzed. The prognostic value of YEATS2 was assessed using Kaplan-Meier analysis, Cox regression and ROC curves, and its regulatory mechanisms were analyzed using KEGG enrichment analysis. In cultured GC cell lines (HGC-27 and AGS), the effect of YEATS2 knockdown and overexpression on migration, invasion and EMT of the cells were examined with scratching assay, Transwell assay and Western blotting. RESULTS: YEATS2 was significantly overexpressed in GC tissues with a positive correlation with Ki67 (<0.05). High YEATS2 expression was associated with elevated CEA (≥5 μg/L), CA19-9 (≥37 kU/L), T3-4 stage, and N2-3 stage (all <0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (<0.001); ROC analysis showed that YEATS2 expression levels had a sensitivity of 80.00% and a specificity of 66.67% for predicting patient survival (<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (: 1.675, 95%: 1.013-2.771; =0.045). KEGG enrichment analysis suggested involvement of YEATS2 in EMT in GC and Wnt/β-catenin signaling. In cultured GC cells, YEATS2 overexpression significantly promoted cell migration and invasion, upregulated the expressions of vimentin, N-cadherin, Wnt and active β-catenin, and downregulated E-cadherin expression, and these changes were obviously suppressed by treatment with XAV-939 (a Wnt/β-catenin inhibitor). CONCLUSIONS: High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.
[Reduced intestinal abundance of increases risk of kidney stones: a Mendelian randomization study and evidence from rat models].
Pan X, Zhang B, Zhang Z … +1 more , Cao Q
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311082 · Full text
OBJECTIVES: To investigate the causal relationship between gut microbiota and kidney stones. METHODS: Mendelian randomization analysis was conducted based on data from the MiBioGen consortium gut microbiota GWAS (exposur...
OBJECTIVES: To investigate the causal relationship between gut microbiota and kidney stones. METHODS: Mendelian randomization analysis was conducted based on data from the MiBioGen consortium gut microbiota GWAS (exposure factors) and the IEU Open GWAS kidney stone dataset ukb-b-8297 (outcome variables) using the inverse variance weighted, MR-Egger regression, weighted median, weighted mode, and simple mode methods. Heterogeneity, pleiotropy, and leave-one-out sensitivity analyses were also performed. In the animal experiment, 12 male SD rats were randomized into control group with saline treatment and kidney stone model group treated with 1% ethylene glycol and 2% ammonium chloride for 28 consecutive days. Urine, blood, and intestinal samples of the rats were collected for testing the changes in renal function and intestinal barrier-related indicators, and kidney and colon pathologies were examined with histological staining and immunohistochemistry. The changes in diversity and abundance of gut microbiota were analyzed using 16S rRNA gene sequencing. RESULTS: Mendelian randomization analysis showed that decreased abundances of NK4A136 group (OR=0.9974, 95% : 0.9948-0.9999, =0.0393) and (OR=0.9987, 95% : 0.9974-0.9999, =0.0403) were associated with an increased risk of kidney stones without significant heterogeneity or horizontal pleiotropy, and sensitivity analyses suggested robustness of the results. The rat models of kidney stones exhibited significant renal function impairment and calcium oxalate crystal deposition, accompanied by decreased expressions of intestinal barrier-related proteins with lowered intestinal α- and β-diversity indices. Intestinal abundance was significantly reduced in the rat models while the NK4A136 group did not differ significantly between the control and model groups. CONCLUSIONS: Decreased abundance in gut microbiota is associated with an increased risk of kidney stones. The protective role of the NK4A136 group against kidney stones as suggested by Mendelian randomization analysis fails to be supported by the experimental evidence and awaits further investigation.
[A heterogeneous graph method integrating multi-layer semantics and topological information for improving drug-target interaction prediction].
Chen Z, Guo Y, Song S … +2 more , Guo Q, Zhou D
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311081 · Full text
OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insuf...
OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insufficient modeling of high-order semantic dependencies, lack of adaptive fusion of semantic paths, and over-smoothing of node features. METHODS: A heterogeneous graph network with multiple types of entities such as drugs, proteins, side effects, and diseases was constructed, and graph embedding techniques were used to obtain low-dimensional feature representations. An adaptive metapath search module was introduced to automatically discover semantic path combinations for guiding the propagation of high-order semantic information. A semantic aggregation mechanism integrating multi-head attention was designed to automatically learn the importance of each semantic path based on contextual information and achieve differentiated aggregation and dynamic fusion among paths. A structure-aware gated graph convolutional module was then incorporated to regulate the feature propagation intensity for suppressing redundant information and redcuing over-smoothing. Finally, the potential interactions between drugs and targets were predicted through an inner product operation. RESULTS: Compared with existing drug-target interaction prediction methods, the proposed method achieved an average improvement of 3.4% and 2.4%, 3.0% and 3.8% in terms of the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC) on public datasets, respectively. CONCLUSIONS: The drug-target interaction prediction method developed in this study can effectively extract complex high-order semantic and topological information from heterogeneous biological networks, thereby improving the accuracy and stability of drug-target interaction prediction. This method provides technical support and theoretical foundation for precise drug target discovery and targeted treatment of complex diseases.
[Elevated TMCO1 expression in gastric cancer is associated poor prognosis and promotes malignant phenotypes of tumor cells by inhibiting apoptosis].
Song B, Zhou R, Xu Y … +8 more , Shi J, Zhang Z, Li J, Geng Z, Song X, Wang L, Wang Y, Zuo L
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311080 · Full text
OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric canc...
OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (<0.05), and its high expression was positively correlated with cancer progression (<0.001) and a lowered postoperative 5-year survival rate of the patients (<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS: TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
[Electroacupuncture improves post-traumatic stress disorder in rats by alleviating hippocampal mitochondrial injury regulating Bcl-2/Bax/caspase-3 signaling].
Ma D, Cheng J, Zhang H … +2 more , Liu G, Song K
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311079 · Full text
OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank contr...
OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining. RESULTS: The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement. CONCLUSIONS: EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
[LncRNA Meg3 expression level is negatively correlated with liver fibrosis severity in patients with Wilson disease].
Hua D, Xuan Q, Sun L … +6 more , Yu Q, Wang Q, Wang T, Ma Q, Yang W, Wang H
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311078 · Full text
OBJECTIVES: To investigate the expression of the long non-coding RNA maternally expressed gene 3 (LncRNA Meg3) in patients with the Wilson disease (WD) and its correlation with the severity of liver fibrosis and autophag...
OBJECTIVES: To investigate the expression of the long non-coding RNA maternally expressed gene 3 (LncRNA Meg3) in patients with the Wilson disease (WD) and its correlation with the severity of liver fibrosis and autophagy-related markers. METHODS: A total of 100 WD patients and 50 healthy individuals were enrolled from the First Affiliated Hospital of Anhui University of Chinese Medicine. Serum biomarkers, including platelet count, hyaluronic acid (HA), laminin (LN), type III procollagen N-terminal peptide (PIIINP), type IV collagen (C‑IV), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were measured, and the non-invasive indices APRI and FIB-4 were calculated. Peripheral blood levels of LncRNA Meg3, Beclin-1 and LC3B were detected using RT-qPCR, and liver stiffness (LSM) and shear wave velocity (SWV) were evaluated using two-dimensional shear wave elastography (2D-SWE). The liver tissues from 10 WD patients and 10 patients with hepatic hemangioma were examined using histochemical staining, transmission electron microscopy, and RT-qPCR. RESULTS: The expression level of LncRNA Meg3 was significantly lower, while the levels of AST, ALT, HA, LN, PIIINP, C‑IV, APRI, FIB-4, LSM and SWV were significantly higher in WD patients than in the healthy individuals (all <0.01). LncRNA Meg3 was negatively correlated with LSM, SWV, APRI, FIB-4, Beclin-1 and LC3B (<0.05). ROC analysis demonstrated that LncRNA Meg3 effectively discriminated >F4 stage fibrosis (AUC=0.902) with a sensitivity of 92.9% and a specificity of 83.7% at the optimal cut-off value, outperforming APRI (AUC=0.746) and FIB-4 (AUC=0.661). The liver tissues from WD patients exhibited characteristic histopathological changes and lowered expression of LncRNA Meg3, which was negatively correlated with Beclin-1 and LC3B expressions (<0.05). Liver fibrosis staging (7 S4 cases and 3 S3 cases) was significantly associated with LSM and SWV levels (<0.05). CONCLUSIONS: The expression level of LncRNA Meg3 is significantly decreased in WD patients, which is negatively correlated with the severity of liver fibrosis and closely related to the level of autophagy.
[Effect of needle-knife release on the median nerve and transverse carpal ligament in rabbits with carpal tunnel syndrome].
Li Y, Zhou Q, Luo S … +3 more , Lin W, Huang X, Cao Y
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311077 · Full text
OBJECTIVES: To investigate the effect of needle knife release on median nerve (MN) and transverse carpal ligament (TCL) morphology and function and expression levels of inflammatory factors in rabbit models of carpal tun...
OBJECTIVES: To investigate the effect of needle knife release on median nerve (MN) and transverse carpal ligament (TCL) morphology and function and expression levels of inflammatory factors in rabbit models of carpal tunnel syndrome (CTS). M Thirty adult New Zealand rabbits were randomized equally into control group, CTS model group, ultrasound-guided needle knife release group, needle knife release group without ultrasound guidance, and sham treatment groups. In all but the control group, the rabbits were subjected to CTS modeling by 10% glucose solution injection into the carpal tunnel once a week for 4 consecutive weeks, followed by interventions with a single treatment session. At 3 days and 30 days after the interventions, 3 rabbits from each group were selected for ultrasound measurement of TCL and MN thickness, electrophysiological testing, ultrasound elastography, and inflammatory cytokine level assessment. RESULTS: In the rabbit models of CTS, ultrasound-guided needle knife release significantly reduced the thickness of TCL and MN and improved sensory nerve conduction velocity at both 3 and 30 days after the intervention. Elastography of the TCL showed markedly softened intra-carpal tissues after ultrasound-guided needle knife release and achieved superior outcomes over those in the other groups. The treatment also significantly reduced IL-17 levels and lowered IL-6 and PGE2 expression at 30 days after the intervention. CONCLUSIONS: Needle knife release of the TCL reduces thickness of the MN and TCL, enhances median nerve function, alleviates intrascatic tissue stiffness, and downregulates inflammatory factors in the carpal tunnel in rabbit models of CTS, and ultrasound guidance further enhances its therapeutic efficacy.
[Association between Tau protein deposition and brain metabolites: N-acetylaspartate and creatine as potential biomarkers for advanced Alzheimer's disease].
Li X, Zhang Y, Gu Y … +5 more , Chen N, Qian X, Zhang P, Hao J, Wang F
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311076 · Full text
OBJECTIVES: To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy (H-MRS) in patients with advanced Alzheimer's disease (AD)....
OBJECTIVES: To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy (H-MRS) in patients with advanced Alzheimer's disease (AD). METHODS: From April, 2022 to December, 2024, 64 Tau-positive AD patients and 29 healthy individuals underwent F-APN-1607 PET/MR and simultaneously acquired multi-voxel H-MRS in the Department of Nuclear Medicine, Nanjing First Hospital. Visual analysis and voxel-based analysis of PET/MR data were performed to investigate the Tau protein deposition patterns in AD patients. Valid voxels within the H-MRS field of view were selected, and their standardized uptake value ratio (SUVr) in PET and metabolite levels of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, and Cho/Cr were recorded. The Tau-positive (Tau) voxels and Tau-negative (Tau) voxels of the AD patients were compared for PET and H-MRS parameters, and the correlations between the metabolites and Tau PET SUVr within Tau voxels were analyzed. RESULTS: Significant Tau protein deposition were observed in the AD patients, involving mainly the bilateral frontal lobes (30.07%), parietal lobes (29.96%), temporal lobes (21.07%), and occipital lobes (15.89%). A total of 1422 valid voxels in AD group (including 994 Tau and 428 Tau voxels) and 814 voxels in the control group were selected. The AD patients showed significantly decreased NAA level and increased SUVr compared with the control group (0.05). Subgroup analyses revealed that Tau voxels had higher SUVr and lower Cr and Cho/Cr than Tau voxels (0.05). Compared with the control group, Tau voxels exhibited higher SUVr and lower Cr (0.05), while Tau voxels showed lower NAA (0.004). No significant differences were found in Cho or NAA/Cr among the subgroups (0.05). Within Tau voxels, NAA, Cho, and Cr were negatively correlated with SUVr (0.001). CONCLUSIONS: The patients with progressive AD have significant Tau protein deposition in the brain, which is correlated with alterations in metabolite levels. Decreased NAA is more prominent in early or pre-tau deposition stages, while Cr changes is more significant in the regions with Tau protein deposition, suggesting the potential of NAA and Cr as biomarkers for Tau protein deposition in AD for disease monitoring and treatment evaluation.
[ polysaccharides alleviates cisplatin-induced granulosa cell injury by downregulating miR-23a].
Liu L, Wang K, Wang X … +1 more , DU B
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311075 · Full text
OBJECTIVES: To evaluate the protective effect of polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. METHODS: Human granulosa-like tumor cell line (KGN)...
OBJECTIVES: To evaluate the protective effect of polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. METHODS: Human granulosa-like tumor cell line (KGN) were treated with 2.5 µg/mL cisplatin for 24 h, followed by treatment with 100, 500, and 1000 mg/L LBP, and the changes in cell viability, apoptosis, level of anti-Müllerian hormone (AMH), and cell ultrastructure were detected with CCK-8 assay, flow cytometry, ELISA and transmission electron microscopy. The cellular expressions of Bax, caspase-3, Bcl-2, and the PI3K/AKT pathway proteins were analyzed using Western blotting, and the expression of miR-23a was detected with RT-qPCR. KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP. RESULTS: Cisplatin treatment significantly inhibited cell viability, induced apoptosis, decreased AMH level, caused ultrastructural abnormalities, increased Bax and caspase-3 expression, and lowered Bcl-2 expression in KGN cells. Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells. LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells, and in particular, LBP treatment at the medium dose for 24 h significantly improved KGN cell viability, reduced apoptosis, enhanced their endocrine function, and ameliorated ultrastructural abnormalities. Mechanistically, medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells, subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2. Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP. CONCLUSIONS: LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway, suggesting a potential therapeutic strategy for ovarian function preservation.
[Molecular mechanism of Pills for improving rheumatoid arthritis in rats: a proteomic analysis].
Li Y, Yang X, Yao X … +1 more , Huang C
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311074 · Full text
OBJECTIVES: To analyze the molecular mechanism of Pills for treatment of rheumatoid arthritis (RA). METHODS: Forty-eight rats were randomized into 6 groups (=8), including a normal control group, a collagen-induced arth...
OBJECTIVES: To analyze the molecular mechanism of Pills for treatment of rheumatoid arthritis (RA). METHODS: Forty-eight rats were randomized into 6 groups (=8), including a normal control group, a collagen-induced arthritis (CIA) model group, 3 Pills treatment (200, 400 and 800 mg/kg) groups, and a Tripterygium glycosides tablet (TGT) treatment group. In the latter 4 groups, the rats were treated with daily gavage of Pills or TGT 2 weeks after CIA modeling for 3 consecutive weeks. The differentially expressed proteins in high-dose Pills group and the model group compared with the normal control group were screened based on the tandem mass spectrometry tag (TMT) technology, and the core targets and signaling pathways were analyzed. The immune cell infiltration and gene expression data were analyzed using ggplot2 and tidyverse packages, and the correlation coefficients between the core targets and the immune cells were calculated. RESULTS: The CIA rats showed significantly increased serum levels of TNF-α and IL-6 and lowered serum IL-10 level. Treatments with high- and medium-dose Pills and TGT all significantly reduced serum TNF‑α and IL-6 and increased IL-10 levels in CIA rats. Proteomic analysis identified 160 differential proteins between the model group and high-dose Pills group, and the core targets included CCL5, STAT1, GZMB and IL7R. The areas under the ROC curve of CCL5 and STAT1 were both greater than 0.9. Immunohistochemical and immunofluorescence staining revealed increased levels of CCL5 and STAT1 in the ankle joints of CIA rats, which were significantly decreased after treatment with Pills. CONCLUSIONS: Treatment with Pills offers protection of the joints in CIA rats possibly by inhibiting joint inflammation via regulating protein expressions of CCL5 and STAT1.
[circ_EPHB4 synergizes with YTHDF3 to promote glioma progression mA-dependent stabilization of Wnt3].
Jin C, Liu J, Liu B … +2 more , Fei X, Liao Y
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311073 · Full text
OBJECTIVES: To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism. METHODS: Microarray analysis was performed to identify the differentially expressed circRNAs in glioma tissu...
OBJECTIVES: To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism. METHODS: Microarray analysis was performed to identify the differentially expressed circRNAs in glioma tissues. The effects of circ_EPHB4 on glioma cell migration, invasion and epithelial-mesenchymal transition (EMT) and tumorigenicity were assessed using scratch wound healing assay, Transwell invasion assay and nude mouse models bearing subcutaneous tumors. RNA immunoprecipitation (RIP), RNA stability assays, and gene overexpression and silencing techniques were employed to validate the synergistic regulatory effect of circ_EPHB4 and the N6-methyladenosine (mA) reader protein YTHDF3 on Wnt3 expression. RESULTS: Circ_EPHB4 was significantly overexpressed by 2.3 folds (|log2FC|=1.2, <0.01) in glioma tissues compared to the adjacent tissues, and by 2.5 folds in glioma cell line U373 compared to normal cells (<0.001). Overexpression of circ_EPHB4 significantly enhanced migration and invasion of glioma cells, and promoted the expressions of EMT markers N-cadherin and vimentin. In the tumor-bearing mouse models, the tumor volume in circ_EPHB4 overexpression group was significantly greater than that in the control group, and the lung metastatic foci increased by 4.2 folds. Overexpression of circ_EPHB4 promoted oncogenesis by upregulating Wnt3 expression, while YTHDF3 extended the half-life of Wnt3 mRNA in an mA-dependent manner. Simultaneous knockdown of circ_EPHB4 and YTHDF3 resulted in an obvious reduction of Wnt3 mRNA expression by up to 47% compared to its level following knocking down either circ_EPHB4 or YTHDF3 alone. CONCLUSIONS: Circ_EPHB4 and YTHDF3 promote glioma progression by jointly targeting the Wnt3 signaling pathway, which may provide a new therapeutic strategy for gliomas.
[ Granules enhances cisplatin sensitivity of ovarian cancer xenografts in rats by regulating adenine nucleotide translocator 3-mediated mitochondrial apoptosis].
Chen Y, Ma M, Su R … +5 more , Zhu Y, Feng Q, Luo J, Feng W, Yan X
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311072 · Full text
OBJECTIVES: To investigate the molecular mechanism by which Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its admi...
OBJECTIVES: To investigate the molecular mechanism by which Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS: LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
[ Granules improves renal damage in MRL/lpr mice by inhibiting B cell differentiation the AIM2/Blimp-1/Bcl-6 axis].
Cheng L, Tang Z, Li M … +4 more , Chen J, Shang S, Liu S, Huang C
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311071 · Full text
OBJECTIVES: To investigate the efficacy of Granules (QJZ) for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism. METHODS: Thirty 8-week-old female MRL/lpr mice were randomly di...
OBJECTIVES: To investigate the efficacy of Granules (QJZ) for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism. METHODS: Thirty 8-week-old female MRL/lpr mice were randomly divided into model group, QJZ group, prednisone (Pred) group, QJZ+Pred group, and AIM2 inhibitor group (=6), with 6 8-week-old female C57BL/6 mice as the normal control group. After treatments with normal saline, QJZ, Pred, or AIM2 inhibitor for 8 weeks, the mice were examined for urinary total protein-to-creatinine ratio (TPCR) and albumin-to-creatinine ratio (ACR), serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal histopathology (with HE, Masson, and PAS staining) and ultrastructural changes (with electron microscopy). ELISA, immunohistochemistry, immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies, cytokines and chemokines, renal deposition of complement components C3 and C4, renal expressions of AIM2, CD19, CD27 and CD138, and changes in splenic B lymphocyte subsets. The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting. RESULTS: QJZ treatment significantly improved Cr, BUN, TPCR and ACR in MRL/lpr mice, ameliorated renal pathologies, reduced the expressions of ds-DNA, BAFF, IL-21, CXCL12, CXCL13, C3 and C4, and increased IL-10 levels. QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1, upregulated Bcl-6 and PAX5 expressions, inhibited B-cell differentiation, and lowered the expressions of AIM2, CD27, CD138 and CD69. Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions, increased Bcl-6 and PAX5 levels, suppressed B-cell differentiation, decreased IgG production, reduced C3 and C4 deposition, and alleviated renal pathology in MRL/lpr mice. CONCLUSIONS: QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.
Rheumatism Plaster ameliorates neuropathic pain in mice by suppressing TLR4/TNF-α signaling.
Fu Y, Tan W, Li X … +3 more , Lin R, Liu S, Ye L
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Nov · PMID 41311070 · Full text
OBJECTIVES: To explore the therapeutic effect of Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with...
OBJECTIVES: To explore the therapeutic effect of Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm, respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of and in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS: LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
[Traditional Chinese medicine for regulating glycolysis to remodel the tumor immune microenvironment: research progress and future prospects].
He S, Liu Y, Qin M … +6 more , He C, Jiang W, Wang Y, Tan S, Sun H, Sun H
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Oct · PMID 41139458 · Full text
Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medi...
Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
[HOTAIR rs920778 single nucleotide polymorphism is associated with breast cancer susceptibility and HER2-targeted therapy resistance in Chinese population].
Zhang M, Sun F, Han Z … +2 more , Gao Y, Luo Y
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Oct · PMID 41139457 · Full text
OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan pro...
OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% : 1.09-2.19; =0.017), an advanced tumor stage (<0.001), lymph node metastasis (<0.001), and the triple-negative subtype (<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% 89.3%, =0.001) and a lower pathological complete response rate after neoadjuvant therapy (=0.018). CONCLUSIONS: The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
[Inhibition of BRD4 promotes migration of esophageal squamous cell carcinoma cells with low ACC1 expression].
Jia W, Huo S, Tang J … +2 more , Liu Y, Zhao B
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Oct · PMID 41139456 · Full text
OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-media...
OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS: BRD4 inhibition promotes autophagy of ESCC cells a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
[ Capsule improves renal vascular endothelial function in rats with diabetic nephropathy by downregulating the Notch1/NICD/MAML1 signaling pathway].
Zhu S, Ma J, Zheng Y … +5 more , Wu C, Zhao J, Li L, Wang L, Zhou X
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Oct · PMID 41139455 · Full text
OBJECTIVES: To investigate the therapeutic mechanism of Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by lef...
OBJECTIVES: To investigate the therapeutic mechanism of Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting. RESULTS: The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC. CONCLUSIONS: DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
[SF3B3 overexpression promotes proliferation of gastric cancer cells and correlates with poor patient prognosis].
Lu H, Song B, Shi J … +5 more , Wang S, Chen X, Yang J, Ge S, Zuo L
Nan Fang Yi Ke Da Xue Xue Bao · 2025 Oct · PMID 41139454 · Full text
OBJECTIVES: To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms. METHODS: SF3B3 expression levels in pan-cancer and GC were analyzed using TIMER2.0, GEPIA, and UA...
OBJECTIVES: To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms. METHODS: SF3B3 expression levels in pan-cancer and GC were analyzed using TIMER2.0, GEPIA, and UALCAN databases and validated using immunohistochemistry in GC tissues. Survival curves of GC patients were established using Kaplan-Meier Plotter and the data of a patient cohort our hospital. The independent risk factors for 5-year postoperative survival were identified using Cox regression, and their predictive values were evaluated using ROC analysis. SF3B3-associated biological processes were predicted by bioinformatics enrichment analyses. In GC HGC-27 cells, the effects of lentivirus-mediated SF3B3 knockdown and overexpression on cell proliferation and migration were investigated, and the changes in the key glycolytic proteins and extracellular acidification rate (ECAR) were detected. The influence of SF3B3 expression level on tumorigenesis and glycolytic protein expression were evaluated in a nude mouse xenograft model. RESULTS: High expression of SF3B3 in GC was associated with poor patient prognosis (<0.05). The factors affecting 5-year survival outcomes following gastric oncological resection included high SF3B3 expression, a CEA level ≥5μg/L, a CA19-9 level ≥37 kU/L, tumor stage T3-4, and lymph node metastasis stage N2-3 (<0.05). Bioinformatics analysis showed significant enrichment of SF3B3 in glycolysis. In HGC-27 cells, SF3B3 knockdown significantly inhibited while SF3B3 overexpression enhanced cell proliferation, migration, and invasion. SF3B3 knockdown obviously decreased the expressions of HK2, PKM2 and LDHA proteins and ECAR in HGC-27 cells, whereas SF3B3 overexpression produced the opposite effect. In nude mouse xenograft models, SF3B3 knockdown significantly reduced tumor mass and downregulated expression of HK2, PKM2 and LDHA proteins, and SF3B3 overexpression induced the opposite changes. CONCLUSIONS: SF3B3 overexpression is associated with poor prognosis of GC patients and promotes GC cell proliferation, migration and invasion possibly by enhancing glycolysis.
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