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Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.
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Objective:To explore the mechanism of B10 cell involved in cardiomyocyte hypertrophy following myocarditis, and to develop potential therapeutic strategies.Methods:BALB/c mice infected with Coxsackie virus B3 induced viral myocarditis model. The expression of angiotensin (ANG)Ⅱ and its receptor in myocarditis mice was detected. The changes of B10 cells in the hearts of control mice and myocarditis mice were analyzed by flow cytometry. After losartan was administered to myocarditis mice, the degree of myocardial inflammation was detected by HE staining, the expression of inflammatory factors was detected by ELISA, the myocardial hypertrophy was detected by wheat germ agglutinin (WGA) staining, and the changes of B10 cells in the heart were analyzed by flow cytometry. The levels of cardiac troponin T (C-TNT) and high mobility group box 1 (HMGB1) protein in neonatal mouse cardiomyocytes treated with ANGⅡ and ANGⅡ+ IL-10 were detected. Cardiomyocytes were treated with ANGⅡ, ANGⅡ+ B10 cells, ANGⅡ+ B10 cells + IL-10 receptor antibody and ANGⅡ+ B cells to detect C-TNT protein levels, and Annexin-V/PI was used to detect the apoptosis of cardiomyocytes. Cardiomyocytes were treated with oxidized HMGB1, reduced HMGB1 and disulfide HMGB1, and C-TNT expression was detected.Results:Coxsackievirus B3 infection caused cardiac hypertrophy, high expression of ANGⅡ and its receptor, and transient increase of B10 cells in mice. Losartan treatment blocked the angiotensin receptor, reduced expansion of B10 cells. B10 cells alleviated apoptosis of cardiomyocytes and inhibited the production of HMGB1 induced by ANGⅡ patch by producing IL-10, thus alleviating viral myocarditis and cardiac hypertrophy.Conclusions:B10 cells may play an important role in myocardial protection in myocarditis.
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High mobility group box 1 (HMGB1), a ubiquitous non-histone protein in the nuclear chromatin of eukaryotic cells, plays an important role in inflammatory diseases, autoimmune diseases and cancer. The function of HMGB1 in the development and progression of tumor varies with its subcellular localization. On one hand, HMGB1 promotes the growth, proliferation, invasion and metastasis of tumor cells, and mediates immune escape and immune tolerance; on the other hand, HMGB1 possesses anti-tumor activity by maintaining the stability of genome, regulating the expression of tumor suppressor genes, inhibiting cell invasion and metastasis and improving the anti-tumor therapeutic effect. In recent years, increasing evidences have suggested that HMGB1 is closely associated with the development of tumor. Therefore, understanding the function of HMGB1 in cancer will provide enlightenment for preventive and therapeutic strategies. This review summarized the dual role of HMGB1 in tumor progression.
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Objective To investigate the prognostic value of platelet to lymphocyte ratio (PLR) for early virological response in Entecavir (ETV)-treated chronic hepatitis B (CHB) patients with genotype C infection.Methods Ninety-one genotype C CHB patients with HBV DNA≥1×105 copies/mL were treated with ETV (0.5 mg/d) for 10-13 days.The correlation between PLR and viral load decline was evaluated by Pearson or Spearman's rank correlation coefficient.Stepwise linear regression analysis was used to establish the prediction model of virological response.Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of PLR for early virological response in ETV-treated patients with genotype C hepatitis B virus (HBV) infection.Results After 10-13 days of ETV treatment, HBV DNA decreased ≥1×lg copies/mL from baseline in 89 cases of the 91 patients, while HBV DNA declined ≥2×lg copies/mL in 65 patients and 4 patients achieved HBV DNA<500 copies/mL.HBV DNA decline was positively correlated with baseline PLR levels (r=0.235 09, P<0.05).After adjustment for age, gender, Hepatitis B e Antigen (HBeAg), and treatment days, HBV DNA decline was still positively correlated with baseline PLR levels (r=0.220 26, P<0.05).Area under curve (AUC) of prediction model including age , baseline aspartate transaminase (AST) and HBV DNA was 0.759 (95% CI : 0.660-0.859, P<0.01).After adding PLR to the prediction model, the AUC was 0.780 (95% CI: 0.685-0.875, P<0.01).Conclusions PLR is predictive to early virological response in ETV-treated CHB patients with genotype C infection.Higher baseline PLR level indicates a better virological response.PLR monitoring should be recommended in CHB patients with antiviral treatment in clinical practice.
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Objective To investigate the correlations of plasma eotaxin-2,soluble tumor necrosis factor receptor(sTNFR) Ⅱ and other cytokines levels with the status of metabolic syndrome(MS) in type 2 diabetic nephropathy (DN) patients treated with maintenance hemodialysis(MHD).Methods Thirty type 2 DN patients with stable pathogenetic conditions and MHD treatment for more than 3 months,thirty newly diagnosed and untreated type 2 diabetes(T2D) patients and thirty healthy volunteers were enrolled in the study.The MS related markers,including blood pressure,waist circumference,body mass index,triglyceride(TG),high density lipoprotein cholesterol(HDL-C),fasting blood glucose (FBG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C) and C reactive protein(CRP),were determined.The expression levels of 40 cytokines were detected with the AAH-INF-G3 antibody microarray,and their correlations with MS related markers were analyzed by the Pearson method.Results The incidence rates of MS in DN patients with MHD and T2D patients were 88.89％ and 33.33％,respectively.Compared with T2D patients and healthy controls,the DN patients had more MS related markers,higher waist circumference and lower body mass index,and their plasma eotaxin-2,I-309 and sTNFR Ⅰ / Ⅱ levels increased significantly.Pearson correlation analysis showed that plasma eotaxin-2 and I-309 levels were positively related to MS risk factors such as TG,FBG and diastolic blood pressure(DBP) levels.Plasma sTNFR Ⅱ and I-309 levels were significantly positively correlated with plasma CRP levels.Conclusion A micro inflammatory state exists in type 2 DN patients with MHD.Abnormal glycolipid metabolism may influence on the immunologic and physiological state of human body,and then form the micro inflammatory state.Eotaxin-2 and I-309 may participate in this chronic and persistent process and further induce renal damage by upregulating sTNFR Ⅰ / Ⅱ levels,which may result in the formation of MS state in type 2 DN patients with MHD.
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Objective To investigate the role of interleukin-17 (IL-17) in spinal dorsal horns in neuropathic pain (NP) in rats and its effect on activation of astrocytes.Methods In vivo experiment Sixty-four male SPF Sprague-Dawley rats,aged 6-8 weeks,weighing 180-200 g,were randomly divided into 3 groups using a random number table:control group (group C,n =16),sham operation group (group S,n =24) and group NP (n =24).The animals were anesthetized with intraperitoneal pentobarbital sodium,the L5,6 spinal nerves of the left side of the rat were gently separated and exposed,tightly ligated with 5-0 silk suture and transected.In group S,the L5,6 spinal nerves of the left side of the rat were only exposed.In group C,no operation was performed.Mechanical pain threshold was measured at day 1 before operation and days 1,3,5,7,10 and 14 after operation.The expression of IL-17,IL-6,IL-1β and tumor necrosis factor-alpha (TNF-α) mRNA in the spinal dorsal horn was determined using quantitative real-time PCR at day 7 and day 14 after operation.At day 7 after operation,the activation of astrocytes in the spinal dorsal horn was detected.In vitro experiment Primarily cultured astrocytes of neonatal rats were randomly divided into 4 groups using a random number table:control group (group C,n=22),10 ng/ml IL-17 group (I10 group,n=18),50 ng/ml IL-17 group (I50 group,n-18) and 100 ng/ml IL-17 group (I100 group,n=22).In I10,I50 and I100 groups,the astrocytes were incubated with the culture medium containing 10,50 and 100 ng/ml IL-17,respectively.The proliferation of astrocytes was detected by MTT at 24,48 and 72 h of incutation or culture.The expression of IL-6,IL-1β and TNF-α mRNA was determined using quantitative real-time PCR.Results In vivo experiment Compared with group C,the mechanical pain threshold was significantly decreased at 3-14 days after operation,the expression of IL-17,IL-6 and IL-1β mRNA in the spinal dorsal horn was up-regualted at 7 days after operation,and the activation of astrocytes was increased in group NP,and no significant change was detected in the mechanical pain threshold at each time point after operation in group S.In vitro experiment Compared with group C,the proliferation of astrocytes was significantly increased at 48 h of incubation in I10 and I50 groups,the proliferation of astrocytes was significantly increased at 48 and 72 h of incubation,and the expression of IL-6 and IL-1β mRNA was up-regulated in I100 group,and no significant change was found in the proliferation of astrocytes in group S.Conclusion Up-regulated expression of IL-17 in spinal dorsal horns may be involved in the maintenance of NP,and the mechanism is related to promoted activation of astrocytes and induced inflammatory responses in rats.
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Objective To investigate the prevalence of genes conferring aminoglycoside resistance in multidrug-resistant strains of Acinetobacter baumannii (MDR-ABA).Methods Multidrug-resistant A.baumannii strains were isolated during the period from August to November 2012 from patients in the affiliated hospital of Jiangsu University and the First Hospital of Zhen-jiang.Kirby-Bauer diffusion method was used to determine the susceptibility of these strains to antimicrobial agents.PCR was performed to detect the aminoglycoside resistance genes.Results The 36 MDR-ABA strains showed high resistance rates to most antimicrobial agents except cefoperazone-sulbactam.The prevalence of the genes conferring aminoglycoside resistance, aac (3)-I,aac (6’)-Ib,aph (3’)-I and armA,was 72.2% (26/36),72.2% (26/36),80.6% (29/36)and 80.6% (29/36), respectively.Conclusions The MDR-ABA strains in this study are highly resistant to antimicrobial agents,which is closely as-sociated with the genes conferring aminoglycoside resistance.
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Objective To detect the expression levels of high mobility group box chromosomal protein 1 (HMGB1) and Th17 cells transcription factors, related cytokines in peripheral blood of rheumatoid arthritis (RA) patients and analyze the relations between HMGB1 and CRP, ESR, RF in RA patients. The other aim of this study is to identify the expression level of HMGBI and the relationship between HMGB1 and Th17 in RA patients. Methods The mRNA levels of HMGB1, RORyt, interleukin (IL)-17 in the peripheral blood mononuclear cells (PBMC) were determined by quantitative real-time PCR (QRT-PCR) from 80 patients with rheumatoid arthritis,including 32 RA patients in stable phase and 48 patients in active phase, and 50 healthy volunteers. The concentration of HMGB1, IL-23, IL-17 in plasma were detected by enzyme linked immunosorbent assay (ELISA), one-way ANOVA and Spearman's correleation were adopted for statistical analysis.Results The mRNAs of HMGBI, RORyt and IL-17 in RA patients were higher than that in healthy control group (P<0.05), especially in active RA patients [ HMGB 1 (0.424±0.262) pg/ml, RORγt (0.34±0.25) pg/ml,IL-17 (1.42±0.38) pg/ml,P<0.01 ] when compared with patients with stable disease. The concentration of HMGB1, IL-23 and IL-17 in the plasma of RA patients was higher than that of the healthy control group (P< 0.05), and was positively correlated with the expression levels of HMGB1, Th 17-associated factors and the level of CRP, ESR, RF in RA patients' plasma(P<0.05). Conclusion The HMGB1 and Thl7 cells levels are higher in active RA patients than those in patients with stable disease, arid there is significant positive correlation between them. Detection of peripheral HMGB1 and Thl7 cell-specific transcription factors or related cytokines can help to understand the development and progress of rheumatoid arthritis and provide clues for new treatment targets for RA.
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Objective To establish a stable orthotopic transplantation nude mouse model of the human pancreatic cancer and to explore the role of monitoring tumor growth with noninvesive MRI.Methods The tumors cells suspension made by the subcutaneous injection of human pancreatic cancer cell lines PANC1 were used as the source of tissue for orthotopic implantation of tissue.and transplanted into the pancreas of 20 BALB/C-nu nude mice.After implantation,the successful rate,tumor formation time,tumor growth speed,tumor shape and the change of signal of the tumor were monitored and recorded noninvasively by MRI.At the end of the 7th week,all the specimens were examined by pathological methods.Results Thirty-five percent (7/20)mice with implantation of primary human PANC1 adenocarcinoma cells were detected to have orthotopic implanted tumors by MRI after 15 days,and all the 20 nude mice developed pancreatic tumor within 27 days after operations,and the successful rate was 100%.Compared with adjacent normal tissue,the T1 WI imaging of 90%(18/20)of all the tumors showed uniformly hypo-intense signal,10%(2/20)showed iso-intense signal,the T2W 75%(15/20)showed uniformly hyper-intense signal.The tumor size 2,3,4,5,6,7 weeks after implantation was(912.6±2.4)mm3,(94.3±11.2)mm3,(175.9±82.5)mm3,(395.8±126.6)mm3,(1290.2±167.2)mm3,(1583.4±87.4)mm3,respectively.Pathologic examination confirmed poody differentiated pancreatic adenocatcinoma and it remained the primary tumor's biolosic features.Conclusions The orthotopic transplantation nude mouse model was in accordance with the feature of human pancreatic cancer and was easy for noninvasive monitoring,which provided an effective and stable in vivo experimental system.
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In order to investigate the effect of T-bet on malignant cells, we selected SGC-7901, a kind of human gastric carcinoma cell line, and used gene clone technique and adeno-associated virus (AAV) packing technology, thus obtaining a recombinant rAAV-eGFP-T-bet and T-bet gene-transfected SGC-7901 cells. Then the function of T-bet gene-infected SGC-7901 cells was researched by detecting the levels of IFN-gamma and T-bet production. The results showed: (1) It was verified that rAAV-T-bet's packing was completed; (2) After SGC-7901 cells was transfected by rAAV-eGFP-T-bet, a green fluorescence was found in about 30%-40% SGC-7901s, and the gene of 1670 bp (T-bet) and 388 bp (IFN-gamma) were generated from SGC-7901s cells; (3) The proteins of IFN-gamma and T-bet secreted by SGC-7901 cells were also detected. These reveal that SGC-7901 cell is efficiently infected by rAAV encoding T-bet, which can induce transfected cells to secret IFN-gamma. It may be useful in the researches on cancer immune therapy of transfecting T-bet gene.
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Humans , Cell Line, Tumor , Dependovirus , Genetics , Metabolism , Green Fluorescent Proteins , Interferon-gamma , Recombinant Proteins , Genetics , Stomach Neoplasms , Genetics , Metabolism , T-Box Domain Proteins , Genetics , TransfectionABSTRACT
Objective To investigate the antimicrobial susceptibility of Pseudomonas aeruginosa (P. aeruginosa) isolated from Zhenjiang area to 13 routinely used antibiotics and identify the structure and dissemination of class Ⅰ integron. Methods K-B test was used to determine the resistant rate of 71 strains of P. aeruginosa. DNA template was extracted by boiling method, PCR method was utilized to detect class Ⅰintegron, and subsequently gene cassettes were analyzed by sequencing. Results The resistant rates to 13 routinely used antibiotics were quite different from 18. 3 to 77.5% among 71 strains of P. aeruginosa. The prevalence of class Ⅰ integron was 38%. These integrons include 5 gene cassettes ( aadB, aac (6) - Ⅱ , PSE-Ⅰ , dfrA17 and aadAS), in which dfrA17 and aadA5 gene cassette were frequently found. Comparing with the negative strains of integron, the positive strains of integron has obviously higher resistance to ten the antibiotics including piporacillin, piperacillin-tazobactam, ceftriaxone, cefepime, ceftazidime, gentamicin,amikacin, tobmmycin, levofloxacin, and ciprofloxacin. Conclusions The resistant rates of P. aeruginosa to 13 drugs were different, and the resistant rates of integron positive strains were obviously higher than integron negative strains, which indicates that integron may play an important role in multidrug reisistance of P. aeruginoosa.
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Avian influenza has emerged as one of the primary public health concern of the 21st century. Influenza strain H5N1 is capable of incidentally infecting humans and other mammals. Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have been transmitted from poultry to humans (by direct or indirect contact with infected birds) in several provinces of Mainland China, which has resulted in 22 cases of human infection and has created repercussions for the Chinese economy. People have been concerned whether a new pandemic will occur in the future. The eradication of pathogenic avian influenza viruses appears to be the most effective way to prevent an influenza pandemic. This paper will examine the features of H5N1, including incidence, infection, immunity, clinical management, prevention and control, and therapy in Mainland China.