南方医科大学学报杂志最新文献

Objectives: To investigate the regulatory effect of Serpin Family E Member 1 (SERPINE1) on immune microenvironment and paclitaxel (PTX) resistance of triple-negative breast cancer (TNBC) cells.

Methods: CCK-8 assay was used to determine the half-maximal inhibitory concentration of PTX in TNBC cell line MDA-MB-231. In wild-type MDA-MB-231 cells and a PTX-resistant MDA-MB-231 cell line (MDA-MB-231/PTX) established by stepwise increasing low-dose PTX treatment, the effects of Western blot-verified transfection with SERPINE1 overexpression plasmids or SERPINE1 siRNAs on cell apoptosis were evaluated using Hoechst 33258 staining and by detecting expression levels of cleaved caspase-3 using Western blotting. The changes in proliferation of the transfected cells were assessed using EdU and CCK-8 assays. The breast cancer cells with different treatments were co-cultured with macrophages, and M1 and M2 polarization of the macrophages were analyzed with flow cytometry and Western blotting. In nude mouse models bearing subcutaneous breast cancer cell xenografts, the effects of SERPINE1 overexpression and knockdown in the engrafted cells on tumor growth and PTX resistance were evaluated.

Results: SERPINE1 overexpression significantly inhibited apoptosis and promoted proliferation of MDA-MB-231 cells, and SERPINE1 knockdown obviously promoted apoptosis and inhibited proliferation of MDA-MB-231/PTX cells. The macrophages co-cultured with SERPINE1-overexpressing breast cancer cells showed enhanced M2 polarization and suppressed M1 polarization with a lowered M1/M2 ratio. In the tumor-bearing nude mouse models, SERPINE1 overexpression in the engrafted cells resulted in significantly accelerated tumor growth.

Conclusions: In MDA-MB-231 cells, SERPINE1 overexpression promotes cell proliferation, inhibits apoptosis, and enhances PTX resistance. SERPINE1 plays a regulatory role in macrophage polarization in the immune microenvironment of breast cancer, and its high expression promotes M2 polarization of the macrophages.

Objectives: To evaluate the effect of resveratrol (RES) on barrier function of mouse brain microvascular endothelial cell monolayers exposed to oxygen/glucose deprivation/reoxygenation (OGD/R) and PM_2.5 and explore the role of mitochondrial fission and fusion in protecting endothelial barrier function.

Methods: Cultured mouse brain microvascular endothelial cells were exposed to OGD/R, treated with PM_2.5 (100 μg/mL) before OGD/R, or pretreated with RES (40 mg/mL) prior to OGD/R+PM_2.5 exposures. The changes in cell viability were examined with CCK-8 assay, and cell permeability was assessed by measuring transendothelial electrical resistance (TEER) and FITC-dextran permeation. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured, and intracellular and mitochondrial ROS levels were detected using fluorescent probes. Mitochondrial morphology in the treated cells was observed using Mito-Tracker Red CMXRos. Western blotting was performed to detect the changes in cellular expressions of the tight junction proteins (ZO-1, occludin, and claudin-5) and mitochondrial dynamics-associated proteins (Drp1, Fis1, Mfn2, and OPA1).

Results: Compared with the normal control cells, the cells exposed to OGD/R or both OGD/R and PM_2.5 showed significantly decreased TEER levels, increased permeability, elevated oxidative stress, and increased ROS fluorescence intensities. Obvious mitochondrial fragmentation and morphological changes in the mitochondria were observed in the exposed cells, which also showed decreased expressions of tight junction proteins and mitochondrial fusion proteins with increased expressions of mitochondrial fission proteins. RES pretreatment of the endothelial cells before the exposures significantly reduced membrane permeability, lowered ROS levels, improved mitochondrial morphology, increased expressions of tight junction and fusion proteins, and decreased fission protein expressions.

Conclusions: RES can protect barrier function of mouse brain microvascular endothelial cell monolayers exposed to OGD/R and PM_2.5 by modulating mitochondrial dynamics, potentially through promoting mitochondrial fusion and inhibiting mitochondrial fission.

Objectives: To investigate the causal relationship between gut microbiota, T-cell function, and the risk of colorectal cancer.

Methods: Gut microbiota data from the MiBioGen database and T-cell and colorectal cancer data from publicly available GWAS datasets were obtained for analyzing the causality between gut microbiota, T-cell subsets, and the risk of colorectal cancer with two-sample Mendelian randomization (MR) analyses, using inverse variance weighting as the primary analytical method supplemented with MR-Egger, weighted median, simple mode, and weighted mode methods. Horizontal pleiotropy was assessed using MR-PRESSO and MR-Egger regression. Cochran's Q test was used to evaluate heterogeneity, and sensitivity analysis was performed using the leave-one-out method.

Results: In the Forward MR analysis of gut microbiota and T cells, 11 gut microbiota species showed causal relationships. Six of these species exhibited positive correlations with T cells, including Prevotella7 (P=0.003), Ruminococcaceae UCG011 (P=0.033), Ruminococcaceae UCG004 (0.010), Ebacterium brachy group (P=0.005), Lachnospiraceae FCS020 group (P=0.028), and Coprobacter (P=0.033), and the remaining 5 species showed negative correlations with T cells. Forward MR analysis of T cells and colorectal cancer suggested that CD25⁺⁺CD45RA^-CD4⁺ non-regulatory T cells were negatively correlated with colorectal cancer risk (IVW: OR=0.935, 95% CI: 0.878-0.995; P=0.035). The analysis of gut microbiota and colorectal cancer suggested that 11 gut microbiota species were causally associated with colorectal cancer, and 6 of them (Eubacterium xylanophilum group, P=0.039; Selenomonadales, P=0.014; Negativicutes, P=0.014; Bifidobacteriaceae, P=0.048; Bifidobacteriales, P=0.048; and Coprococcus1, P=0.033) showed positive correlations and the remaining 5 showed negative correlations.

Conclusions: Coprobacter spp. and Eubacterium xylanophilum group spp. are causally associated with both T cell activity and colorectal cancer risk, and the former bacteria induce inactivation of CD25⁺⁺CD45RA^-CD4⁺ non-regulatory T cells to promote colorectal cancer progression, whereas the latter bacteria promote CD25⁺⁺CD45RA^-CD4⁺ non-regulatory T cell activity to inhibit colorectal cancer development.

Objectives: To investigate the potential mechanism underlying the protective effect of secoisolariciresinol diglucoside (SDG) against chronic kidney disease (CKD) in offspring mice caused by maternal exposure to trans fatty acids (TFA) during pregnancy and lactation.

Methods: Thirty female C57BL/6 mice were randomized into control group, TFA model group, and 3 TFA model groups treated with SDG at low, medium and high doses (10, 20 and 30 mg/kg, respectively). The changes in blood urea nitrogen (BUN) and serum creatinine (CRE) levels of the mice were measured. Network pharmacology analysis was conducted to explore protective mechanism of SDG against TFA-induced renal injury, and molecular docking was used to assess the binding affinity of SDG to Bcl-2, Bax, and caspase-3. The protein expressions of cleaved caspase-3, Bax, and Bcl-2 in the renal tissues of the offspring mice were detected with Western blotting.

Results: The mice in TFA group showed significantly higher BUN and CRE levels than those in the control group. Treatment with SDG at the medium and high doses significantly reduced BUN and CRE levels in the mouse models. Network pharmacology and molecular docking suggested that SDG ameliorated renal injury by targeting the apoptosis-related Bcl-2/Bax/caspase-3 axis. The results of Western blotting showed the mouse models in TFA exposure group had increased renal cell apoptosis with elevated expression levels of cleaved caspase-3 protein and a decreased Bcl-2/Bax ratio (P<0.05), and intervention with SDG at all the 3 doses significantly reduced renal cell apoptosis and renal expression of cleaved caspase-3 and increased the Bcl-2/Bax ratio in the mouse models.

Conclusions: Maternal TFA exposure during gestation and lactation induces renal injury in offspring mice. Dietary SDG intervention can mitigate TFA-induced renal injury in offspring mice possibly by suppressing renal cell apoptosis via regulating the Bcl-2/Bax/caspase-3 signaling axis.

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 (P<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 P<0.05). Patients with high YEATS2 expression had significantly reduced 5-year survival (P<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 (P<0.05). Cox regression identified high YEATS2 as an independent risk factor for poor postoperative 5-year survival outcome of GC patients (HR: 1.675, 95%CI: 1.013-2.771; P=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.

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). Methods 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.

Objectives: We propose a multimodal model integrating social media text and image data for automated assessment of psychological stress in college students to support the development of intelligent mental health services in higher education institutions.

Methods: Based on deep learning technology, we designed an evaluation framework comprising a text sentiment modeling module, an image sentiment modeling module, and a multimodal fusion prediction module. Text sentiment features were extracted using Bi-LSTM, and image semantic cues were extracted via U-Net. A feature concatenation strategy was used to enable cross-modal semantic collaboration to achieve automatic identification of 3 psychological stress levels: mild, moderate, and severe. We constructed a multimodal annotated dataset using social platform data from 1577 students across multiple universities in Guangdong Province. After data cleaning, 252 samples were randomly selected for model training and testing.

Results: In the 3-classification task, the model demonstrated outstanding performance on the test set, and achieved an accuracy of 92.86% and an F1 score of 0.9276, exhibiting excellent stability and consistency. Confusion matrix analysis further revealed the model's ability to effectively distinguish between different pressure levels.

Conclusions: The multimodal psychological stress assessment model developed in this study effectively integrates unstructured social behavior data to enhance the scientific rigor and practical applicability of psychological state recognition, and thus provides support for developing intelligent psychological service systems.

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 P<0.01). LncRNA Meg3 was negatively correlated with LSM, SWV, APRI, FIB-4, Beclin-1 and LC3B (P<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 (P<0.05). Liver fibrosis staging (7 S4 cases and 3 S3 cases) was significantly associated with LSM and SWV levels (P<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.

Objectives: To explore the therapeutic effect of LuoFuShan 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 cm², 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 Tlr4 and Tnf-α 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.

Objectives: To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy (¹H-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 ¹⁸F-APN-1607 PET/MR and simultaneously acquired multi-voxel ¹H-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 ¹H-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 ¹H-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 (P<0.05). Subgroup analyses revealed that Tau⁺ voxels had higher SUVr and lower Cr and Cho/Cr than Tau^- voxels (P<0.05). Compared with the control group, Tau⁺ voxels exhibited higher SUVr and lower Cr (P<0.05), while Tau^- voxels showed lower NAA (P=0.004). No significant differences were found in Cho or NAA/Cr among the subgroups (P>0.05). Within Tau⁺ voxels, NAA, Cho, and Cr were negatively correlated with SUVr (P<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.