南方医科大学学报杂志最新文献

Objectives: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect.

Methods: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability.

Results: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential.

Conclusions: Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.

Objectives: To construct a GA-BP neural network model based on the spectrum-effect relationship of Cassia seeds extract and test its performance for quality control of Cassia seeds using spectrum-effect score.

Methods: The HPLC fingerprints of Cassia seeds extract (0.1, 0.2, and 0.4 g/mL) were established. In a mouse model of 5-Fu-induced liver injury treated with 0.4, 0.8, and 1.6 g/kg of Cassia seeds extract, the pharmacodynamics parameters were measured to calculate the comprehensive efficacy using AHP-EWM. A GA-BP neural network model between the fingerprints and comprehensive efficacy was constructed, and the corresponding predicted comprehensive efficacy was obtained. The spectrum-effect relationship between the fingerprints and the measured and predicted comprehensive efficacy was established using grey correlation method followed by Gaussian fitting analysis. The spectral efficiency score was calculated using the relative peak area of the fingerprints and the correlation degree of the spectral efficiency. The reliability of the data was tested using the Z-ratio score method. The limit range of the spectral efficiency score was determined and the quality of the verification samples was evaluated.

Results: The error between the predicted value using the GA-BP neural network model and the measured value of the comprehensive efficacy was less than 0.2. Gaussian fitting analysis showed good fitting between the spectrum-effect relationship data of the measured and predicted comprehensive efficacy. The limit of the spectral efficiency score was 6.16-7.30. The prediction results for each verification group were consistent with the experimental results and within the limit of spectral efficiency score, and the results of Z-ratio score analysis demonstrated good data reliability.

Conclusions: The GA-BP neural network model can effectively predict the comprehensive efficacy of Cassia seeds extract, and the established spectrum-effect scoring method can be used for quality evaluation of samples.

Objectives: To revise and evaluate the psychometric properties of the Chinese version of the Wong and Law's Emotional Intelligence Scale (WLEIS).

Methods: The 11 items of the original WLEIS were modified to form the WLEIS-CR, with the Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), and Flourishing Scale (FS) as the validity criteria. A total of 1546 adult participants were evaluated using all these scales, and a retest was conducted among 192 college students to assess the item discrimination, reliability, validity and measurement invariance of the modified WLEIS-CR.

Results: All the 16 items of the modified WLEIS-CR demonstrated good discriminative power (r=0.570 -0.764, P<0.001). The structural equation model from a confirmatory factor analysis showed excellent fit indices (χ²/df=4.610, GFI=0.965, PGFI=0.674, RMR=0.028, NFI=0.975, CFI=0.980, RMSEA=0.048). The criterion-related validity of the modified WLEIS-CR with FS, GAD-7, and PHQ-9 was 0.674, -0.347, and -0.368, respectively (P<0.001). The internal consistency (Cronbach's α) was 0.913 for the total scale and ranged from 0.867 to 0.916 for the subscales. The split-half reliability was 0.956 for the total scale and 0.865-0.924 for the subscales. Test-retest reliability was 0.701 for the total scale and 0.610-0.684 for the subscales. Normative interpretation criteria were established: 7.6% of participants had "low", 19.3% had "below average", 22.3% had "moderate", 34.3% had "above average", and 16.5% had "very high" emotional intelligence. The scale demonstrated a good measurement invariance across gender, identity, and age groups.

Conclusions: The modified WLEIS-CR has good reliability, validity and measurement invariance, and is suitable for evaluating emotional intelligence of Chinese adults to assess their emotional health.

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.

Objectives: To investigate the efficacy of Lactobacillus plantarum ZG03 (L. plantarum ZG03) for ameliorating oxidative stress in zebrafish.

Methods: We evaluated the growth pattern of L. plantarum ZG03, observed its morphology using field emission scanning electron microscopy, and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis. FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish. In a zebrafish model of 2% glucose-induced oxidative stress, the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue (CHT), superoxide dismutase (SOD) activity, reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content. Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids (SCFAs) in the zebrafish, and the antioxidant effects of the key metabolites (acetate, propionate, and caproate) were tested.

Results: On MRS agar, L. plantarum ZG03 formed circular, smooth, moist, and milky-white colonies with a rod-shaped cell morphology. Genomic analysis revealed abundant sugar metabolism gene clusters. After inoculation of FITC-labeled L. plantarum ZG03 in zebrafish, green fluorescence was clearly observed in the intestinal bulb, mid-intestine, and hind intestine. In zebrafish with glucose-induced oxidative stress, L. plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity. L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid, propionic acid, and caproic acid in zebrafish metabolites. In addition, sodium acetate, sodium propionate, and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models.

Conclusions: L. plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites, particularly the SCFAs including acetic acid, propionic acid and caproic acid.

Objectives: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS).

Methods: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice.

Results: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins.

Conclusions: MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.

Objectives: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects.

Methods: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting.

Results: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells.

Conclusions: High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.

Objectives: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA).

Methods: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting.

Results: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats.

Conclusions: Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.

Objectives: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features.

Methods: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins.

Results: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice.

Conclusions: Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.

Objectives: To explore the toxic mechanism of Clostridium perfringens Beta1 toxin mediated by P2X7 receptor-induced calcium dyshomeostasis.

Methods: Ten-day-old BALB/c mice were randomly divided into control group, recombinant Beta1 toxin (rCPB1) group, PD151746 group, and PD151746+rCPB1 group, and all the treatment agents were administered by gavage. The changes in expressions of inflammatory factors in the jejunum of the mice were detected using antibody chip technology to explore the regulatory role of calcium dyshomeostasis in Beta1 toxin-induced inflammatory injury level. In the cell experiment, THP-1 cells were transfected with a si-RNA targeting P2X7 receptor and treated with rCPB1, and the changes in cell survival rate, levels of Ca²⁺, ROS and ATP, and expressions of pyroptosis and ferroptosis markers were determined.

Results: Oral administration of rCPB1 significantly increased the levels of inflammatory cytokines in the jejunal tissue of the neonatal mice, but their levels were significantly decreased after treatment with PD151746. In THP-1 cells, rCPB1 treatment significantly decreased cell survival and increased the levels of Ca²⁺, ROS, ATP and the expressions of pyroptosis and ferroptosis markers, and these changes were obviously attenuated by P2X7 receptor knockdown.

Conclusions: P2X7 receptor-mediated functional pore formation by Beta1 toxin can further lead to calcium dyshomeostasis, thereby triggering excessive accumulation of ROS to subsequently induce the co-occurrence of pyroptosis and ferroptosis.