Hepatitis B e Antigens ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans

Acute Disease ; Biomarkers, Tumor ; analysis ; Child ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Histocytochemistry ; Humans ; Leukemia ; metabolism ; pathology ; Proliferating Cell Nuclear Antigen ; analysis ; Proto-Oncogene Proteins c-bcl-2 ; analysis

OBJECTIVEAnalyze Naive and Mermory T cell subsets in HIV/AIDS patients and investigate their relationship with disease development.

METHODST cell subsets from 15 normal control subjects, 79 HIV/ AIDS patients were detected by FCM.

RESULTSWith diesase progression, CD4+ Naive cell counts and ratio was both decreased obviously (P < 0.001); CD4+ Tcm cell counts was significantly decreased (P < 0.001), CD4+ Tcm cell ratio was obviously higher (P = 0.002); CD4 TEM cell ratio was obviously increased( P < 0.001); CD8+ T Naive cell counts and ratio was also decreased obviously (P < 0.05); CD8+ T(CM), T(EM), T(EMRA) are not significantly different.

CONCLUSIONSThe peripheral lymphocyte subsets in HIV/AIDS patients changed obviously. The counts of naive T cell decreased, while the proportion of memory T cell increased significantly. It will help to understand pathogenesis of HIV.

Acquired Immunodeficiency Syndrome ; immunology ; virology ; Adult ; CD4 Lymphocyte Count ; Case-Control Studies ; Female ; HIV ; immunology ; Humans ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment.

METHODSForty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks.

RESULTSForty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis.

CONCLUSIONSOur study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Female ; Hepacivirus ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferons ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVESTo study the relationship between liver pathology and clinical characters of chronic HBV carriers.

METHODSAnalyze the age, sex, grade of liver inflammation and stage of liver fibrosis among patients with chronic HBV carriers (n = 58) and non-active HBsAg carriers (n = 32), and compare the grade of liver inflammation and stage of liver fibrosis in different groups according to age, ALT levels and with/without HBeAg. The data was processed by using t test or Chi-square test for statistical analysis, respectively.

RESULTS(1) No differences existed in gender composition ratio between chronic HBV carriers and non-active HBsAg carriers. However, the ages of non-active HBsAg carriers group (35.2+/-7.6) were much older than that of the HBV carriers group (24.7+/-4.8) (t = 2.576, P = 0.017). (2) The stage of liver fibrosis in non-active HBsAg carriers group was more aggravated than that of the chronic HBV carriers group (Chi-square = 23.231, P less than 0.01), whereas no significant differences existed between these 2 groups (Chi-square = 0.058, P = 0.972). (3) As to the grade of liver inflammation and the stage of liver fibrosis, significant differences existed between the groups with higher level of serum ALT (20-40 U/L) and lower level ( is less than or equal to 20 U/L) (Chi-square = 7.827, P = 0.008; Chi-square = 14.303, P = 0.001), and similar results also existed between elder group (more than 40) and younger group (is less than or equal to 40) (Chi-square = 10.949, P = 0.001; Chi-square = 21.271, P less than 0.01); (4) Among the chronic HBV carriers, significant differences existed in grade of liver inflammation between groups with HBeAg positive and negative patients (Chi-square = 10.275, P = 0.002), and the latter was more aggravated; however, there was no difference in stage of liver fibrosis between them (Chi-square test = 3.457, P = 0.178).

CONCLUSIONLiver histopathology can be recommended to guide the clinical diagnosis and treatment, especially for the chronic HBV carriers, with elder age, ALT close to normal and HBeAg negative.

Adolescent ; Adult ; Age Factors ; Biopsy ; Carrier State ; pathology ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; pathology ; virology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Iron is involved in the virulence and pathogenic effects of certain intracellular parasites.In the pathogenic process of Brucella,the uptaking and metabolism of host iron are closely related to intracellular parasitism and immunity escape of Brucella.In this paper,we elucidated the iron transport system,iron response regulators and nutrient immunity of iron based on the latest report and data about Brucella.

OBJECTIVETo analyze defective homologous chromosomal recombination in Han Chinese azoospermic patients.

METHODSTesticular biopsy samples from 7 healthy controls and 7 Han Chinese azoospermic patients including 2 obstructive azoospermia (OA group) and 5 non-obstructive azoospermia (NOA group) were analyzed. Immunofluorescence staining was performed to categorize early stage cells at meiosis prophase and to analyze chromosome pairing and recombination of pachytene spermatocyte. Newly developed meiotic proteins antibodies (anti-SCP3, anti-synaptonemal complex proteins 3, anti-MLH1, anti-Mut-L Homolog 1, anti-CREST, chromosome centromere antibody) were used to identify synaptonemal complex (anti-SCP3), recombination sites (anti-MLH1) and centromere (anti-CREST), respectively. Staging of spermatocyte was determined according to SCP3 formation progression. Qualitative data were compared by a Chi-square test, and ANOVA was used to analyze quantitative data.

RESULTSRespectively, 2346 and 2932 spermatocytes were categorized in the controls and azoospermic patients. The proportions of zygotene cells in both OA group and NOA group were significantly higher than that of the control group. Investigation of 1967 pachytene cells from the controls and 354 pachytene cells from azoospermic patients indicated that the mean MLH1 foci per pachytene cell of NOA group was statistically lower than that of the controls. Compared with the controls, incomplete synaptonemal complexes cells (containing gap and/or split) were significantly increased in the NOA group.

CONCLUSIONDelayed meiosis prophase is relatively common in azoospermic patients, and changes in quantity and distribution of recombination foci may be the cause for spermatogenesis arrest in Han Chinese population.

Adult ; Asian Continental Ancestry Group ; Azoospermia ; genetics ; metabolism ; pathology ; Humans ; Male ; Meiosis ; genetics ; Middle Aged ; Recombination, Genetic ; Spermatocytes ; metabolism ; Synaptonemal Complex ; genetics ; Young Adult

OBJECTIVETo investigate the efficacy and safety of an extended course (96-week) of combination treatment with peginterferon alfa-2a (Peg-IFNa-2a; 40 kd] plus adefovir (ADV) for treating chronic hepatitis B (CHB) in Chinese patients with negativity for hepatitis B e antigen (HBeAg).

METHODSA total of 25 consecutive patients with HBeAg-negative CHB were administered Peg-IFNa-2a (135-180 mug/week) plus ADV (10 mg/day) for 96 weeks. All patients were followed-up for 24 weeks after treatment completion. Levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HbsAg) were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescent microparticle immunoassay, respectively, at 12-week intervals throughout the treatment course and at the end-of-follow-up (week 120). Patients underwent serological analysis at 3-6 month intervals during treatment and follow-up to evaluate occurrence of adverse events; serological parameters included blood count, markers of liver, kidney and thyroid function, and levels of autoantibodies and creatine kinase.

RESULTSFor all patients, the 96-week course of Peg-IFNa-2a plus ADV reduced the level of HBV DNA below the detection threshold (less than 500 copies/ml by FQ-PCR). The overall rate of HBsAg seroconversion was 12% (3/25) at week 48, 28% (7/25) at week 96, and 32% (8/25) at week 120. The occurrences of adverse events were similar at week 48 and week 96.

CONCLUSIONThe extended-course Peg-IFNa-2a plus ADV combination therapy achieved a 100% virological response and better rates of HBsAg seroconversion than 48 weeks of therapy, without a decrease in safety.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the sensitivity of imatinib mesylate (IM) on Sup-B15 Ph⁺ acute lymphoblastic leukemia (ALL) cells knockdown of VE-cadherin (CD144), and to further explore its mechanism.

METHODSCD144 in Sup-B15 leukemia cells was stably knock downed via lentivirus-mediated RNA interference (named as Sup-B15/shVEC). The inhibitory effects of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were measured by CCK-8 test, and the apoptosis of those cells was determined by AnnexinV/7-AAD dyeing using flow cytometry, the percentage of CD34⁺CD38⁻ leukemia cells also by flow cytometry. ALDH1 mRNA levels were detected by real-time RT-PCR, and protein levels of CD144, CD133, Bcr-abl and β-catenin by Western blot.

RESULTSIM treatment presented inhibitory effects on Sup-B15/shVEC and Sup-B15 leukemia cells at multiple concentrations of IM. The IC50 of IM on Sup-B15/shVEC and Sup-B15 leukemia cells were 25.1μmol/L and 18.7μmol/L, respectively (P<0.05). After 48h of 20 μmol/L IM treatment, the percentages of apoptosis cell in Sup-B15/shVEC cells and Sup-B15 cell were (13.52±2.06)% and (3.03±0.72) %, respectively (P<0.05). The percentage of CD34⁺CD38⁻ cells in Sup-B15 cells was significantly higher than in Sup-B15/shVEC cells [(2.39±0.28)% vs (0.96±0.07)%, P<0.05). As compared to Sup-B15 cells, the transcription of ALDH1 in Sup-B15/shVEC was remarkably downregulated, and the CD133 protein level was also downregulated in Sup-B15/shVEC cells. Both cytoplasmic and nucleic β-catenin protein levels (but not for Bcr-abl levels) decreased in Sup-B15/shVEC cells as compare to Sup-B15 cells.

CONCLUSIONKnockdown of CD144 sensitized Sup-B15 Ph+ ALL cells to IM. The possible mechanisms underlying this phenomenon might be via inhibiting β-catenin nucleic translocation and facilitating β-catenin degradation.

Antigens, CD ; genetics ; Benzamides ; pharmacology ; Cadherins ; genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; Endothelium, Vascular ; drug effects ; metabolism ; Gene Knockdown Techniques ; Humans ; Imatinib Mesylate ; Piperazines ; pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; metabolism ; Pyrimidines ; pharmacology ; RNA Interference ; beta Catenin ; metabolism

BACKGROUNDTransplantation of mensenchymal stem cells (MSCs) has been proposed as a promising way for tissue engineering. However, the application of MSCs for transplantation will undergo apoptosis due to the extremely harsh microenvironment such as excessive inflammation. Apigenin (API) has been reported to protect cells against inflammatory damage and cell death by exhibiting anti-inflammatory and anti-oxidative capacity. Here we investigated the modulatory effects of API in lipopolysaccharide (LPS)-mediated inflammation and apoptosis of MSCs, and further defined the underlying mechanism.

METHODSEffects of different concentrations of API (0, 5, 10, 20, 40 and 80 µmol/L) for 24 hours, and LPS (0, 0.5 and 5.0 µg/ml) for 6 hours and 24 hours on MSCs viability were assayed by MTT. Based on this, MSCs were pretreated with different concentrations of API (0 - 40 µmol/L) at the indicated times (6, 12 and 24 hours) followed by exposure to 5 µg/ml LPS for 24 hours. MTT, phase-contrast microscopy, annexinV/propidium iodide (PI) double stain flow cytometry (FCM) and Hoechst staining were applied to explore the effects of API on MSCs induced by 5 µg/ml LPS for 24 hours. In addition, reverse-transcription polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression of pro-inflammatory factors including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), pro-apoptotic gene caspase-3, Bad, and anti-apoptotic gene Bcl-2. Moreover, AutoDock software was used to imitate the docking score of API and vitamin D receptor (VDR). In parallel, Western blotting and RT-PCR were used to investigate protein and mRNA expression of VDR.

RESULTSMSCs stimulated with LPS 5 µg/ml for 24 hours was used as a model of apoptosis induced by over inflammatory stimulus. API (0 - 40 µmol/L) had non-toxic effect on MSCs; however, it could decrease mRNA expression of COX-2, iNOS and NF-κB at different time points in MSCs induced by LPS, except for API at the concentration of 5 µmol/L.

RESULTSfrom phase-contrast microscopy, MTT, Hoechst staining and AnnexinV/PI double stain FCM demonstrated that with the increasing concentrations of API and extension of administrating time, significant morphological changes of MSCs occurred, viability of cells was strongly inhibited, and meanwhile, apoptosis of LPS-administrated MSCs was exacerbated, compared with LPS individual group. In addition, API promoted caspase-3, Bad mRNA expression and inhibited Bcl-2 mRNA expression in a time-dependent and concentration- dependent manner. Further study found that pro-apoptosis effect of API was related to suppress VDR expression.

CONCLUSIONSAPI could inhibit the expression of inducible inflammatory factors, therefore exert the strong anti-inflammatory function. However, API could not protect MSC apoptosis induced by LPS but amplified the apoptosis. The apoptosis is related to Bad/Bcl-2 increasing and caspase-3 activation, which is mediated through suppressing VDR expression.

Animals ; Apigenin ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Cell Survival ; drug effects ; Cells, Cultured ; Flow Cytometry ; Lipopolysaccharides ; pharmacology ; Male ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitriol ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction