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Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
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BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.
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Background@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*Methods@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*Results@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*Conclusion@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.
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OBJECTIVE@#To explore effects of exercise on the expression of adiponectin mRNA and protein in visceral adipose tissue, plasma adiponectin concentration, and insulin resistance of aged obese rats.@*METHODS@#Male SD rats age to 21 days old were fed with high-fat diet (fat percentage was 36.3% to 40.0%) for three stages of adolescence, maturity and old age to establish elderly obesity rats model. When the rats aged to 60 weeks old, natural growing elderly rats were randomly divided into control group (C) and aged exercise group (AE), =6; elderly obesity rats were randomly divided into obesity control group (OC) and obesity exercise group (OE), =6. The treadmill grade was 0°, the exercise speed and time were 15 m/min×15 min, 4 groups each time, between consecutive groups the rats had 5 minutes rest, the rats were exercised for 60 minutes every day, five days a week, continuous exercise for 8 weeks. Then, the expressions of adiponectin mRNA and protein in visceral adipose tissue were determined. The concentrations of blood glucose, plasma adiponectin and insulin were measured. Insulin resistance was calculated.@*RESULTS@#Comparison with control group, the expressions of adiponectin mRNA and protein were obviously decreased, the concentration of blood glucose and insulin resistance were significantly increased in obesity control group, while the expressions of adiponectin mRNA and protein were obviously increased. Comparison with obesity control group, the expressions of adiponectin mRNA and protein, the concentration of plasma adiponectin were obviously increased, the concentration of blood glucose and insulin resistance were significantly decreased in obesity exercise group.@*CONCLUSIONS@#Adiponectin mRNA and protein expression in visceral adipose tissue is decreased and accompanied by high blood glucose and insulin resistance in elderly obesity rats. Exercise can increase the adiponectin mRNA and protein expression in visceral adipose tissue, elevate levels of plasma adiponectin, and decrease the level of blood glucose and insulin resistance in elderly obesity rats.
Subject(s)
Animals , Male , Rats , Adiponectin , Adipose Tissue , Blood Glucose , Insulin Resistance , Obesity , Rats, Sprague-DawleyABSTRACT
PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.
Subject(s)
Animals , Mice , Apoptosis , Aspartate Aminotransferases , Blotting, Western , Calcium , Carrier Proteins , Cholesterol , Collagen , Cytokines , Fibrosis , Hepatocytes , In Situ Nick-End Labeling , Inflammation , Liver , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , TriglyceridesABSTRACT
Objective Meningiomas in the trigone of the lateral ventricle are characterized by deep location and low inci-dence. A few studies have been done on its treatment at home and abroad. This study was to explore the access,techniques,and clini-cal effect of microsurgery for lateral ventricular trigone meningiomas (LVTM). Methods We retrospectively analyzed the clinical data about 36 cases of LVTM treated by microsurgery in our hospital from December 2011 to December 2015. The operation involved lumbar cistern tube drainage, intraoperative drainage of cerebrospinal fluid, a unilateral parieto-occipital U-shaped cut, approach through the interparietal fissure,a sagittal incision about 3 cm long at the interparietal fissure for exposure and resection of the tumor. We followed up the patients for a mean of 17 months postoperatively and analyzed the results and complications. Results Simpson grade I removal of the tumors was achieved in all the 36 cases. Postoperative complications included homonymous hemianopia in 4 cases, central nervous system infections in 3,secondary epilepsy in 2,subcutaneous hydrops in 2,and intratumoral hemorrhage in 1 (which necessitated a second operation). Extended temporal horn of the right lateral ventricle occurred at 32 months after surgery,which was treated by fistulation. Homonymous hemianopia was improved in 2 of the 4 ca-ses. All the patients were capable of daily life activities and none experienced recurrence. Conclusion Sufficient preoperative evalu-ation of the tumor characteristics,rational selection of surgical approach,and expert operation techniques are the key factors for the mi-crosurgical treatment of meningiomas in the trigone of the lateral ventricle.
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To investigate the anti-inflammatory mechanisms of taurochenodeoxycholic acid (TCDCA), the molecule structure file of TCDCA was downloaded from PubChem database, PharmMapper and GeneCards were used to predict and screen the targets of TCDCA. STRING database and Cytoscape software were used to construct protein interactions network. GO and KEGG analysis was preformed through STRING database. The key targets were validated by molecular docking and the targets type was attributed by DisGeNET database. The network showed that 89 targets were involved in 68 biological processes including response to stimulus, multicellular organismal process, single-multicellular organism process, response to chemical, response to organic substance, by adjusting 51 signaling pathways, such as pathways in cancer, progesterone-mediated oocyte maturation, MAPK signaling pathway, proteoglycans in cancer. These findings provide an overview of anti-inflammation of TCDCA, which reflects the characteristic of multi-targets and multi-pathways of TCDCA. It pointed out the direction for further research on anti-inflammatory mechanism of TCDCA.
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Objective By detecting the distribution and homology analysis of Acinetobacter baumanii in the ICU ward,to con-trol nosocomial infection,provide theoretical basis to take effective measures.Methods From January 2016,20 patients in ICU of Shaanxi Provincial People's Hospital were taken into group.The samples of sputum and surrounding environment samples were cultured.The homology of Acinetobacter baumannii was analyzed by MALDI-Biotyper software,antimicrobial susceptibility test was analyzed by K-B.Results 27 strains of Acinetobacter baumannii were detected,mainly comes from sputum,hands of medical staffs and the environment,homology analysis results showed that the 27 strains of Acinetobacter baumannii was divided into two clusters(Ⅰtype 1 1 strains,Ⅱ type 1 6 strains),most of Acinetobacter baumannii were multi-resistant bacteria,except for the polymyxin B,minocycline and SCF.Conclusion The ways of transmission of Acineto-bacter baumanii in ICU were by medical personnel hand,pollution of the medical equipment and so on,strengthening the dis-infection and reasonable application of antimicrobial agents were taken advantageous for the prevention and control of acine-tobacter baumannii infection and transmission.
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AIM:To analyze of refractive status after vitrectomy combined with phacoemulsification in patients with vitreoretinal disease and cataract.METHODS:A total of 150 patients with vitreoretinal disease and cataract were treated in our hospital from January 2014 to November 2016.According to the random number table method they were divided into two groups:combination group (75 cases) with vitrectomy combined with phacoemulsification,the control group (75 cases)with vitrectomy first,then phacoemulsification surgery.The recovery of visual acuity and the change of the axial length of the eyes were observed.The patients were followed up for 6mo,and the postoperative complications were recorded.RESULTS:After treatment,number of patients in the two groups with visual acuity ≥ 0.1 were significantly improved compared with before treatment (P＜0.05),and the percent in combination group was 95％,higher than 63％ in the control group (P＜0.05).There were no significant changes in the axial length before and after the operation in the two groups (P＞0.05),and there was no significant difference between the groups before and after treatment (P＞0.05).The refractive status of combination group shifted to myopia,that of control group shifted to hyperopia,two groups had no statistically significant difference on numerical prediction (P ＜ 0.05).The difference was statistically significant on the actual values (P＜0.05).The complication rate in the combination group was 24％,which was lower than 40％ in the control group,and the difference was statistically significant (P＜0.05).CONCLUSION:Vitrectomy combined with phacoemulsification on vitreoretinal diseases with cataract patients is effective,and safety,clinical application value is higher.
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Objective@#To investigate the effect of small interfering RNA silencing the vitamin D receptor (VDR) on the biological behavior of prostate cancer PC-3 cells.@*METHODS@#We constructed the VDR-shRNA lentiviral vector and determined the mRNA and protein expressions of VDR by RT-PCR and Western blot. Using scratch wound healing and Transwell chamber assays, we detected the changes in the migration and invasiveness of the PC-3 cells after silencing VDR.@*RESULTS@#The VDR-shRNA plasmid significantly interfered the VDR expression and successfully screened the cell lines with stable VDR-shRNA interference. The rate of scratch wound healing was markedly lower in the VDR interference group than in the blank control and LV3 negative control groups (59% vs 73.6% and 77.8%, P 0.05), and so was the count of permeable cells (P 0.05). The migration ability and invasiveness of the VDR-treated cells were remarkably decreased as compared with those of the control cells.@*CONCLUSIONS@#Down-regulated expression of the VDR gene may reduce the migration and invasiveness of prostate cancer cells.