南方医科大学学报杂志最新文献

Objective: To investigate the correlation of CEP192 expression with prognosis of gastric cancer and biological behaviors of gastric cancer cells.

Methods: Public databases and clinical tissue samples were used to examine CEP192 expression level in gastric cancer. Kaplan-Meier survival curves, univariate and multivariate Cox regression analyses, ROC curves and bioinformatics analyses were used to explore the risk factors affecting the 5-year postoperative survival, the correlation of CEP192 expression level with the patients' survival, and its biological role in gastric cancer development. In gastric cancer MGC-803 cells with lentivirus-mediated CEP192 interference or overexpression, cell proliferation and expressions of PLK1, CDK1 and Cyclin B1 were examined with CCK-8 assay and Western blotting. The effects of CEP192 knockdown or overexpression on tumorigenesis of MGC-803 cells was observed in nude mice, and the expressions of PLK1, CDK1 and Cyclin B1 in the xenografts were detected.

Results: CEP192 was highly expressed in gastric cancer and associated with poor prognosis of the patients (P < 0.05). High expression of CEP192, CEA ≥5 ng/mL, CA199 ≥37 IU/mL, T3-4 stage, and N2-3 stage were independent risk factors affecting the patients' 5-year postoperative survival (P < 0.05). Bioinformatics analyses suggested that CEP192 was involved in several vital biological processes and positively regulated cell cycle progression. In MGC-803 cells, CEP192 knockdown significantly inhibited cell proliferation and lowered the expression levels of PLK1, CDK1, and Cyclin B1, while its overexpression produced the opposite effects. In the nude mouse models, CEP192 knockdown resulted in lowered tumorigenic potential of MGC-803 cells and decreased protein levels of PLK1, CDK1, and Cyclin B1 in the xenografts, while CEP192 overexpression in MGC-803 cells caused the opposite changes.

Conclusion: CEP192 overexpression is correlated with unfavorable outcomes of gastric cancer patients and promotes gastric cell proliferation by regulating the key proteins during G2/M phase transition.

Objective: To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.

Methods: Thirty-six male C57BL/6 mice were randomly divided into control group, model group, maggot (1.25%, 2.5%, and 5%) groups, and Benvitimod (1%) group. Psoriasis-like lesions were induced by application of imiquimod cream, and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index (MPASI) score. Auricular swelling of the mice was observed, and histopathological changes of the skin lesions were examined with HE staining. Scratching behavior of the mice was observed and the spleen index was calculated. Toluidine blue staining was used to detect mast cells in the skin lesions, and serum levels of IgG, IgM, the complements CH50, C1s, C3, C3a, C5 and C5a, and the inflammatory factors IL-23, IL-17A and TNF-α were determined with ELISA.

Results: In mice with imiquimod-induced psoriasis-like skin lesions, treatment with the maggot at the 3 doses significantly decreased MPASI score, alleviated auricular swelling and pathologies in the skin lesions, reduced scratching behaviors, spleen index, and the number of mast cells in the lesions. Treatment with high-dose maggot significantly lowered serum levels of IgG, C1s, C3a, C5a, IL-23, IL-17A and TNF- α and the levels of C1s, C3, C3a, C5 and C5a in the lesion tissue, and increased serum levels of CH50, C3, and C5. The therapeutic effect of maggot showed a dose-effect dependence.

Conclusion: Maggot can alleviate psoriasislike skin lesions in mice by inhibiting immune stress and complement activation.

Objective: To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.

Methods: C57Thy1-YFP/GAD67-GFP mice were randomized into control group (with no treatment) and chronic unpredictable mild stress (CUMS) group (n=15) subjected to CUMS for 8 weeks. Depression-like behaviors of the mice were assessed using sucrose preference test, open field test, and forced swimming test, and their spatial learning and memory abilities were evaluated using Morris water maze test. The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala (CeA) and the prelimbic cortex (PrL) using whole-cell patch-clamp technique.

Results: Compared with the control mice, CUMS mice showed significantly decreased sucrose preference, total distance moved, number of grid-crossings, entries into the central area, and time spent in the central area in the open field test (P < 0.01). In the forced swimming test, CUMS mice exhibited obviously shortened time of struggling, swimming, and climbing with increased immobility time. In Morris water maze test, CUMS mice showed significantly increased escape latency and path length, decreased percentage of distance and swimming time within the target quadrant, and increased first entry latency into the target zone and swimming time within the opposite quadrant. Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL, while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.

Conclusion: CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Objective: To explore the therapeutic mechanism of Liuwei Buqi (LWBQ) Formula for chronic obstructive pulmonary disease (COPD) in rat models.

Methods: SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide (LPS) instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks, starting at the 5th week of modeling. After the treatments, the rats were examined for lung pathologies, lung function, total cell count and white blood cell count in bronchoalveolar lavage fluid (BALF), and serum levels of IL-6, TNF-α, IL-18 and NO. The mRNA expressions of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in the lung tissue were detected with qRT-PCR.

Results: Compared with the normal control rats, the COPD rat models had severe lung pathologies and showed significantly decreased lung function, increased total cell and leukocyte subset counts in BALF, and increased serum levels of IL-6, TNF-α, IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue. Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function, reduced total cell and leukocyte counts in BALF, and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue. The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference, but BALF cell counts, serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment.

Conclusion: LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.

Objective: To study the influence of implant depth and scanning rod lengths on the accuracy of digital impression for single-tooth implant restoration of the mandibular posterior teeth.

Methods: Five standard dental cast models with missing right mandibular first molar (46) were prepared with the subgingival implant depths of 0, 1, 3, 5 and 7 mm. ITI RC and ITI RC H11 scanning rods were connected to the replacement body and placed into the seating tract for scanning. The reference data were obtained using a 3D dental scanner, and the experimental data were obtained by 10 scans of each model using a digitized intraoral scanner. Geomagic Wrap 2021 was used to analyze the model data to test the trueness and precision of the models.

Results: The trueness did not differ significantly among the groups (P > 0.05). The implant depth of 1 mm achieved the highest impression precision (66.81±2.45 μm), and the depth of 0 mm resulted in a significantly lower precision (95.60±3.04 μm) than the depth of 1 and 3 mm. Starting from the subgingival depth of 1 mm, the precision of the scan decreased progressively with the increase of the implant depth. At the subgingival implant depth of 5 or 7 mm, the use of an extended rod significantly improved the scan precision.

Conclusion: For single-tooth implant restoration of the mandibular posterior teeth, the implant depth can substantially affect the accuracy of digital impression, which decreases as the implant depth increases. For a deep implant, the use of a longer scanning rod can improve the scanning accuracy.

Objective: To investigate the effect of E₂ signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.

Methods: Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury, followed by intramuscular injection of β-estradiol (E₂) or 4-hydroxytamoxifen (4-OHT). The changes in serum E₂ of the mice were detected using ELISA, and the number, phenotypes, and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry. C2C12 cells were induced to differentiate into mature myotubes, which were treated with IFN- γ for 24 before treatment with β -Estradiol or 4-OHT. The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio, followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation, and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.

Results: Compared with the control mice, the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates, with increased M1 cell percentage, reduced M2 cell percentage and macrophage efferocytosis in the injured muscle, and obviously delayed myofiber regeneration and repair. In the cell co-culture systems, treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis, while 4-OHT treatment resulted in the opposite changes.

Conclusion: In injured mouse skeletal muscles, myofiber E₂ signaling promotes M1 to M2 transition to increase macrophage efferocytosis, thereby relieving inflammation and promoting muscle regeneration and repair.

Objective: To explore the mechanism of electroacupuncture pretreatment (EP) for relieving post-stroke spasticity in rats.

Methods: Eighteen rats were randomized equally into sham-operated group, middle cerebral artery occlusion (MCAO) group, and MCAO+EP group. In MCAO+EP group, the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO. Neurological deficits and cognitive function of the rats were evaluated, and pathologies in the hippocampus were examined using HE, Nissl, and TUNEL staining. The expressions of IL-4, IL-6, TNF-α, and TMAO in the brain tissues were detected with ELISA, and the mRNA and protein expression levels of NF-κB p65, NLRP3, caspase-3, and caspase-9 were determined with qRT-PCR, Western blotting, and immunohistochemistry.

Results: The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension, number of apoptotic neurons, and expressions of IL-6, TNF-α, NF-κB p65, NLRP3, caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition. Microscopically, the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries. In contrast, the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores, reduced cell apoptosis, lowered hippocampal expressions of IL-6, TNF-α, caspase-3, caspase-9, and NF-κB p65, increased time for new object recognition, tightly arranged and uniformly stained hippocampal cells with clear boundaries, with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.

Conclusion: EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Objective: To investigate the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.

Methods: Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde (MDA) contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen (PCNA) using RT-qPCR and Western blotting. Human liver cancer Huh-7 cells were treated with Erastin (a ferroptosis inducer), Fer-1 (a ferroptosis inhibitor), or both, and the changes in expression levels of MDA, ACSL4 and PCNA were detected, and the cell proliferation was assessed with plate cloning assay.

Results: MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues. In Huh-7 cells, Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA, suppressed cell proliferation, and increased MDA contents. Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions, cell proliferation and MDA contents.

Conclusion: ACSL4 level is significantly overexpressed in liver cancer. Erastin increases MDA contents and down-regulates ACSL4 expression, thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells, and these effects can be reversed by Fer-1.

Objective: To analyze the factors affecting the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by essential hypertension (EH) and explore the impact of EH on HCC risk in patients with CHB-Cir.

Methods: This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department, Third Affiliated Hospital of Xinxiang Medical University from January, 2017 to January, 2024. The cases with insufficient follow-up time or missing data were excluded. The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group. The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups, and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk.

Results: A total of 390 CHB-Cir patients (274 male and 116 female patients) were enrolled in this study, including 195 with EH and 195 without EH. In these patients, EH was significantly correlated with the occurrence of HCC (HR=1.69, P=0.002). Multivariate analysis suggested that the male gender (HR=1.73, P=0.005), a family history of liver cancer (HR=2.23, P < 0.001), elevated alpha-fetoprotein (HR=2.83, P=0.001), elevated glutathione reductase (HR=1.53, P=0.046), reduced high-density lipoprotein (HR=1.46, P=0.027), and elevated low-density lipoprotein (HR=2.29, P=0.003) were all significantly correlated with HCC occurrence, while elevated triglycerides (HR= 0.37, P < 0.001) was a protective factor against HCC. In the EH group, treatment with non-RASIs drugs (HR=2.77, P=0.021) and no treatment/diuretic treatment (HR=7.18, P < 0.001) were significantly correlated with HCC occurrence.

Conclusion: Hypertension increases the risk of HCC in patients with CHB-Cir, suggesting the importance of controlling hypertension in these patients.

Objective: To investigate the protective effect of total flavonoids of Salvia divinorum extract against acetaminophen (APAP) -induced acute liver injury (ALI) and its molecular mechanism.

Methods: The main chemical constituents of total flavonoids of Salvia divinorum were obtained through literature search, and their pharmacological mechanisms were predicted using bioinformatics analysis. In a mouse model of APAP-induced ALI, the protective effects of 100, 200 and 400 mg/kg total flavonoids of Salvia miltiorrhiza and 150 mg/kg bifidus were evaluated by observing changes in blood biochemistry and liver histopathology and detecting expressions of the key proteins in the Nrf2/HO-1 signaling pathway.

Results: Network pharmacology analysis suggested that the main active components in total flavonoids of Salvia divinorum for regulating APAPinduced liver injury included quercetin, lignocerol, caruric acid, and kaempferol, for which GO function enrichment analysis yielded 632 GO entries, including 472 involving biological processes, 42 involving cellular composition, and 118 involving molecular function. KEGG enrichment analysis showed that the total flavonoids of Salvia divinorum regulated APAP-induced liver injury mainly through ferroptosis-related signaling pathway. In mice with APAP-induced ALI, treatment with the total flavonoids significantly lowered ALT and AST levels, improved liver histopathology and inflammatory cell infiltration, reduced iron deposition in liver tissues, improved lipid peroxidation-related indexes, promoted the expressions of Nrf2, HO-1, SLC7A11, and GPX-4 proteins, and inhibited the expression of keap1 protein.

Conclusion: The total flavonoids of Salvia divinorum alleviate APAP-induced ALI in mice possibly by suppressing hepatocyte ferroptosis via activating the Nrf2/SLC7A11/GPX-4 signaling pathway.