Objective : To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods: Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results: The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.

We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.

We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

Prostate cancer(PCa)ranks as the second most prevalent malignancy among males worldwide at present,and its prevalence keeps rising.Focal therapy not only results in tumor necrosis but also encourages the release of autoantigens originating from the tumor into the bloodstream and activates the host immune system to effectively fight the tumor.However,focal therapy alone may not achieve the total ablation of cancer cells and may cause locoregional recurrence.Immunotherapy,by boosting the body's immune re-sponse,destroys tumor cells and prevents immune escape.Recent studies show that focal therapy combined with immunotherapy can produce a better clinical efficacy by enhancing the initial immune response,especially for low-to intermediate-risk confined PCa.This article offers some fresh perspectives on the management of PCa by reviewing the etiology and progression of the malignancy,focal ther-apeutic options,and advantages and vista of focal therapy combined with immunotherapy.

To evaluate e-cigarette vaping-induced respiratory toxicity and the interventional effects of air cleaners. A randomized controlled trial study of toxic vaping by the respiratory tract were conducted at the Key Laboratory of Environmental Medical Engineering, Ministry of Education, the School of Public Health, Southeast University from January to December 2022. 8-week-old male C57BL/6JGpt mice selected with a random number table method were used to establish a vaping-exposure model at different periods (0 d, 3 d, 7 d or 14 d), or exposed to clean air as a control group. Mice were exposed to regular heated vaping (200 ℃) and high-temperature heated vaping (280 ℃). Total lung RNA was extracted from control and e-cigarette exposed mice for transcriptome sequencing analysis. Reactive Oxygen Species (ROS) generation and mitochondrial membrane potential (MMP) were detected by flow cytometry. Total superoxide dismutase (SOD) and superoxide (O^2-) were evaluated using a microplate reader. Real-Time Quantitative PCR (RT-qPCR) was used to detect gene expression. Air filter and ionizer were used to intervene the toxicity of vaping. Data were expressed as (x¯±s), differences between multiple groups were compared using one-way or two-way ANOVA. The results showed that, RNA sequencing assays suggested that the differential genes between the control and vaping exposure groups were significantly enriched in the oxidative stress (Fold Enrichment=3.18) and mitochondrial oxidative phosphorylation (OXPHOS) (Fold Enrichment=5.74) pathways. Both types of heated vaping exposure caused significantly increased the score of alveolitis (F=10.8, P<0.001), increased endogenous ROS generation (F=16.8, P<0.001), decreased MMP (F=13.6, P<0.01), and gene expression of mitochondrial complex I dysfunction. The toxic effects of high-temperature heated vaping were stronger compared to regular heated vaping (F=2.9, P<0.05). The filter demonstrated better protective effects against vaping than the ionizer by reducing pulmonary alveolitis (F=7.4, P<0.01). Air cleaners could partially alleviate oxidative stress and mitochondrial dysfunction. In conclusion, this study demonstrate that vaping brings potential health risks. Air cleaners could partially reverse mitochondrial dysfunction, but cannot completely prevent the toxic effects, effective interventions remain to be investigated.
Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Electronic Nicotine Delivery Systems ; Reactive Oxygen Species ; Vaping ; Mitochondrial Diseases

To evaluate e-cigarette vaping-induced respiratory toxicity and the interventional effects of air cleaners. A randomized controlled trial study of toxic vaping by the respiratory tract were conducted at the Key Laboratory of Environmental Medical Engineering, Ministry of Education, the School of Public Health, Southeast University from January to December 2022. 8-week-old male C57BL/6JGpt mice selected with a random number table method were used to establish a vaping-exposure model at different periods (0 d, 3 d, 7 d or 14 d), or exposed to clean air as a control group. Mice were exposed to regular heated vaping (200 ℃) and high-temperature heated vaping (280 ℃). Total lung RNA was extracted from control and e-cigarette exposed mice for transcriptome sequencing analysis. Reactive Oxygen Species (ROS) generation and mitochondrial membrane potential (MMP) were detected by flow cytometry. Total superoxide dismutase (SOD) and superoxide (O^2-) were evaluated using a microplate reader. Real-Time Quantitative PCR (RT-qPCR) was used to detect gene expression. Air filter and ionizer were used to intervene the toxicity of vaping. Data were expressed as (x¯±s), differences between multiple groups were compared using one-way or two-way ANOVA. The results showed that, RNA sequencing assays suggested that the differential genes between the control and vaping exposure groups were significantly enriched in the oxidative stress (Fold Enrichment=3.18) and mitochondrial oxidative phosphorylation (OXPHOS) (Fold Enrichment=5.74) pathways. Both types of heated vaping exposure caused significantly increased the score of alveolitis (F=10.8, P<0.001), increased endogenous ROS generation (F=16.8, P<0.001), decreased MMP (F=13.6, P<0.01), and gene expression of mitochondrial complex I dysfunction. The toxic effects of high-temperature heated vaping were stronger compared to regular heated vaping (F=2.9, P<0.05). The filter demonstrated better protective effects against vaping than the ionizer by reducing pulmonary alveolitis (F=7.4, P<0.01). Air cleaners could partially alleviate oxidative stress and mitochondrial dysfunction. In conclusion, this study demonstrate that vaping brings potential health risks. Air cleaners could partially reverse mitochondrial dysfunction, but cannot completely prevent the toxic effects, effective interventions remain to be investigated.
Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Electronic Nicotine Delivery Systems ; Reactive Oxygen Species ; Vaping ; Mitochondrial Diseases

The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
Mice ; Animals ; Insular Cortex ; Peroneal Nerve ; Mice, Inbred C57BL ; Neuralgia ; GABAergic Neurons ; Analgesia ; Analgesics ; Receptors, Cannabinoid

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

Humans ; Hemangioma ; Liver Neoplasms ; Fever