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Qi-Chang Zheng, Guo-Dong Chen,
Ming-Zhu Kong,
Guo-Qiang Li,
Jia-Yu Cui,
Xiao-Xia Li,
Zu-Yan Wu,
Liang-Dong Guo,
Ying-Zhou Cen,
Yi-Zhi Zheng,
Hao Gao
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ABSTRACT: Two new 4-methyl-progesteroids, nodulisporisteriod A (1) and nodulisporisteriod B (2), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1), along with two related metabolites, demethoxyviridin (3) and inoterpene B (4). Their structures were determined by detailed spectroscopic analyses, X-ray crystallographic analysis and comparison of the NMR data with those of the closely related compounds previously reported. Nodulisporisteriod A (1) and nodulisporisteriod B (2) possess new carbon skeletons, which are the first cases of fission at C-3,4 in 4-methyl-progesteroids. A hypothetical biosynthetic pathway for 1 and 2 was proposed. Moreover, the Aβ42 aggregation inhibitory activities of 1-4 were evaluated using standard thioflavin T (ThT) fluorescence assay with epigallocatechin gallate (EGCG) as positive control. Demethoxyviridin (3) displayed anti-Aβ42 aggregation activity with IC50 value of 13.4 μM.
Steroids 05/2013; · 2.83 Impact Factor
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ABSTRACT: Five new xanthoquinodins, A4-A6 (1-3), B4 (4), and B5 (5), were isolated from the crude extract of the endolichenic fungal strain Chaetomium elatum (No. 63-10-3-1), along with three known xanthoquinodins, A1-A3 (6-8). Their structures were determined by detailed spectroscopic analysis and comparison of the NMR data with those of the closely related compounds previously reported. The absolute configuration of 1 was established by X-ray crystallographic analysis and ECD calculation. The cytotoxic activity of all compounds was tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines.
Journal of Natural Products 04/2013; · 3.13 Impact Factor
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ABSTRACT: Chemical investigation on an endolichenic fungal strain Scopulariopsis sp. led to the isolation of two new naphthalene derivatives, 1-(4'-hydroxy-3',5'-dimethoxy-phenyl)-1,8-dimethoxynaphthalen-2(1H)-one (1) and 1,8-dimethoxynaphthalen-2-ol (2). Their structures were determined by spectroscopic techniques (UV, IR, MS, 1D, and 2D NMR).
Journal of Asian natural products research 08/2012; · 0.61 Impact Factor
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ABSTRACT: Three new azaphilones, chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3), and two new chlorinated phenolic glycosides, globosumoside A (4) and globosumoside B (5), were isolated from the crude extract of the fungal strain Chaetomium elatum No. 89-1-3-1. Their structures were determined by detailed NMR and MS spectroscopic analyses. The absolute configurations of C-7 in chaetomugilin S (1), 7,5'-bis-epi-chaetoviridin A (2), and 7-epi-chaetoviridin E (3) were assigned by CD experiments, and the absolute configurations of 1 and 2 were established by X-ray crystallography. Compounds 1-3 are the first examples of 7R-configurated azaphilones with a chlorinated isochromen from Chaetomium spp. In addition, compounds 1-3 showed inhibitory activity in the cysteine aspartyl-specific protease-3 (caspase-3) enzymatic assay, with IC50 values of 20.6, 10.9, and 7.9 µM, respectively.
Planta Medica 08/2012; 78(15):1683-9. · 2.15 Impact Factor
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ABSTRACT: Two new heptaketides, (+)-(2S,3S,4aS)-altenuene (1a) and (-)-(2S,3S,4aR)-isoaltenuene (2a), together with six known compounds, (-)-(2R,3R,4aR)-altenuene (1b), (+)-(2R,3R,4aS)-isoaltenuene (2b), 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (3), alternariol (4), alternariol-9-methyl ether (5), and 4-hydroxyalternariol-9-methyl ether (6) were isolated from the EtOAc extract of an endolichenic fungal strain Nigrospora sphaerica (No.83-1-1-2). Compounds 1a and 1b were separated from enantiomers 1 by chiral HPLC, and so were 2a and 2b from enantiomers 2. Interestingly, 1-6 were also obtained from other two endolichenic fungal strains Alternaria alternata (No.58-8-4-1) and Phialophora sp. (No.96-1-8-1). The structures of 1-6 were elucidated by means of MS, HR-MS, NMR, and X-ray diffraction. Furthermore, the absolute configurations of 1a-2b were determined by CD experiments and CD calculation. Of these compounds, 4 and 5 showed antiviral activity against herpes simplex virus (HSV) in vitro, with IC(50) values of 13.5 and 21.3 μM, and with selective index (SI) values of 26.5 and 17.1, respectively.
Fitoterapia 05/2012; 83(6):1087-91. · 1.85 Impact Factor
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ABSTRACT: To determine the incidence of BK virus associated nephropathy (BKVAN) in renal-transplantation recipients, observe its histological features.
A total of 137 renal allograft biopsy specimens collected at our hospital during December 1999 to January 2008 were analyzed by routine histologic examination, immunohistochemistry and transmission electron microscopy (TEM) to screen for BKV. The case records of involved recipients were accessed to know their clinical manifestations, diagnostic characteristic and treatment regimens at that time. And the 1-, 3-year graft survival rate were analyzed by Kaplan-Meier analysis.
A total of 16 renal biopsy specimens (11.7%) were positive for BKV. Viral particales on the size of 35 - 40 nm were seen in the tubular epithelial cells of 3 biopsy specimens and 7 urinary sediment samples. The numbers of BKVAN recipients suffering acute rejection, using ALG/ATG/OKT3 and using FK506+MMF immunosuppressive protocol were 7, 7 and 10 respectively. In 14 cases of BKVAN, there was an elevated level of serum creatine concentrations. Four cases lost their grafts after using a large dose of immunosuppressives. And renal functions improved by a reduction of immunosuppression or a replacement of FK506 with CsA in 8 cases. And graft functions deteriorated or had already failed in the remaining 4 cases whose immunosuppressive protocol were not changed. The 1-, 3-year graft survival rates were 81.3% and 54.2% in BKVAN recipients respectively.
The diagnosis of BKVAN should be considered in recipients when their graft functions are deteriorating, especially for those with the accompanied risk factors. The morphological hallmarks of BKVAN are similar to those of acute rejection. The differentiation may be made by either immunohistochemistry or TEM. A proper modification of maintenance immunosuppression is effective in slowing down the progression of BKVAN.
Zhonghua yi xue za zhi 09/2011; 91(34):2402-6.
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ABSTRACT: We hypothesized that the T helper (Th)17 response plays an important role in murine cytomegalovirus (MCMV) interstitial pneumonia. BALB/c mice with skin grafts from C57/BJ6 mice were intranasally inoculated with 1.0 × 10(5) PFU MCMV. Lung tissues and skin grafts were histologically evaluated and expression of interleukins (IL)-17, -6 and -8, monocyte chemotactic protein (MCP)-1 and interferon (IFN)-γ in serum and bronchoalveolar lavage (BAL) fluid, intracellular IL-4, -17, and IFN-γ, in spleen lymphocytes were analysed. The levels of IL-17 in the serum and BAL fluid were significantly higher in MCMV-infected mice versus not-infected mice (P = 0.0286 and P = 0.007, respectively) and the BAL levels of IL-17 peaked in 9 days (P = 0.001). The IL-17 level in the BAL was correlated with the grade of lung interstitial inflammation (r = 0.554, P = 0.0144). Serum IFN-γ levels were also higher after infection than that in the not-infected mice (P = 0.0286). IL-17 production increases locally and systemically during MCMV interstitial pneumonia. Neutralization of IL-17 significantly suppressed lung inflammation at day14 as assessed by histology. These findings suggest that IL-17 is important in the pathology of MCMV interstitial pneumonia.
Transplant International 05/2011; 24(8):845-55. · 2.92 Impact Factor
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ABSTRACT: To assess the prevalence and predictors of post-transplant diabetes mellitus (PTDM) in Chinese renal recipients and describe their long-term evolution of glucose metabolism.
887 non-diabetic Chinese adult renal recipients were studied retrospectively, with a median follow-up of 7 years. PTDM patients were categorized into transient PTDM and permanent PTDM. The cumulative incidence and risk factors of PTDM were estimated by Kaplan-Meier and Cox regression.
The cumulative incidence of PTDM at 3 months, 1, 3, 5, 10, 15 and 20 years post-transplant was 10.4%, 11.4%, 13.4%, 15.2%, 22.7%, 27.9% and 38.3%, respectively. 61.9% of PTDM cases were diagnosed within the first three months and 61.6% of them developed persistent diabetes in the future. Risk factors for all PTDM included older age, body mass index (BMI)≥25 kg/m(2), triglycerides≥1.5 mmol/L, rejection, the use of tacrolimus and diltiazem. The predictors of permanent PTDM included age >50 years (RR=2.322, 95% CI 1.255-4.296, P=0.007), BMI≥25 kg/m(2) (RR=1.699, 95% CI 1.014-2.846, P=0.044) and the use of tacrolimus (RR=1.835, 95% CI 1.181-2.851, P=0.007).
Patients were most susceptible to PTDM within the first three months post-transplant and more than half of them developed persistent diabetes in the future. Age >50 years, overweight and tacrolimus application were risk factors for both PTDM and permanent PTDM.
Diabetes research and clinical practice 01/2011; 92(1):11-8. · 2.16 Impact Factor
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ABSTRACT: To study the anatomy characters of renal artery and the treatment of multiple arteries in living donor renal grafts.
Records of 142 living donors were analyzed in our center. We analyzed the anatomic structure of renal arteries by DSA and CTA pre-transplantation. Thirty-one kidneys with multiple arteries were transplanted after reconstruction. Then clinical effects were compared between multiple-renal-arteries group (n=31) and single-renal-artery group (n=111).
The incidence of multiple renal artery was 30.99%, and there was no difference between both sides (left kidney 22.54%, right kidney 22.13%). If the multiple artery occurred in left or right kidney, the incidence of the multiple artery occurred in the other side was 56.25% and 60.00%, respectively. The diameter of left main renal artery was more magnanimous (P=0.001) and the first branch was more closed to abdominal aorta (P=0.004). Operation time and warm/cool ischemia time were longer in the multiple-renal-arteries group. However, estimated blood loss, delayed graft function, acute rejection and flow rate of arcuate artery were similar in both groups, the same as serum creatinine and serum creatinine clearance rate on day 7, 1 month and 3 month post-operation. It was shown by repeated measures ANOVA that graft with multiple arteries didn't affect the tendency of renal function at early time post-operation.
Comprehending the character of renal artery and accurate treatment of multiple artery anastomosis are critical for the effect of the living kidney transplantation.
Zhonghua wai ke za zhi [Chinese journal of surgery] 12/2009; 47(24):1879-82.
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Gang Huang,
Li-Zhong Chen,
Jiang Qiu,
Chang-Xi Wang,
Ji-Guang Fei,
Su-Xiong Deng,
Jun Li, Guo-Dong Chen,
Lei Zhang,
Qian Fu,
Wen-Tao Zeng,
Da-Qiang Zhao
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ABSTRACT: BK virus (BKV)-associated nephropathy (BKVAN) in renal transplant recipients is an important cause of renal transplant dysfunction. Our aim was to determine the kinetics of BKV load within one yr after kidney transplantation under the impact of intensive monitoring and reduction in maintenance immunosuppression, the incidence of BKVAN, and the outcome of BKVAN treatment.
Urine and peripheral blood (PB) were taken from 90 renal transplant recipients for BKV cytological testing and real-time PCR for BKV DNA at one, three, six, nine, and 12 months after transplantation and treatment. Graft biopsies and urinary sediments of recipients with BKVAN were taken to monitor viral particles by conventional transmission electron microscopy (TEM).
By one post-transplant year, urinary decoy cells (median, 8/10 HPF), BKV viruria (median, 2.60 × 10(5) copies/mL), viremia (median, 9.65 × 10(3) copies/mL), and BKVAN occurred in 42.2%, 45.6%, 22.2%, and 5.6% of patients, respectively. The incidence of BK infection was lower in patients who received cyclosporine A (CsA) (28.9%) compared to tacrolimus (FK506) (57.7%) (p = 0.007). An increased hazard of BK infection was associated with the use of FK506 (HR 2.6, p = 0.009) relative to CsA. After reduction in immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction, or graft loss. BKVAN was diagnosed in five patients (5.6%). The treatment of immunosuppression reduction was effective (i.e., decreased the viral load and number of decoy cells, and improved graft function) in our five patients with BKVAN. Quantitative count of decoy cells (e.g., >10 per 10 HPF) as a marker of viremia and BKVAN had increased positive predictive values of 85.7% and 57.1%, respectively.
Choice of FK506 as immunosuppressive agent is an independent risk factor affecting BKV infection. Monitoring and pre-emptive of immunosuppression reduction were associated with resolution of viremia and showed effective in BKVAN recipients at the early stage without acute rejection or graft loss. Quantitative count of urine cytology is a very convenient, useful, and sensitive method for evaluating BKV infection in renal transplant recipients.
Clinical Transplantation 11/2009; 24(5):599-609. · 1.67 Impact Factor
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ABSTRACT: Two new oxidized sterols 1 and 2 were obtained from the active fraction of a mangrove fungus Aspergillus awamori isolated from the soils around the mangrove plant Acrostichum speciosum. Their structures were elucidated using spectroscopic methods as 22E-7alpha-methoxy-5alpha,6alpha-epoxyergosta-8(14),22-dien-3beta-ol (1) and 22E-3beta-hydroxy-5alpha,6alpha,8alpha,14alpha-diepoxyergosta-22-en-7-one (2). The NMR data and complete assignments for both DMSO-d(6) and CDCl(3) were given. Their cytotoxic activity against A549 cell line was evaluated. Furthermore, the detailed conformation analysis for ring B (cyclohexene oxide system) of sterol 1 was given on the basis of NOEs. The endo-boat conformation was considered as the preferred conformation for ring B rather than half-chair conformation.
Magnetic Resonance in Chemistry 10/2009; 48(1):38-43. · 1.44 Impact Factor
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ABSTRACT: To analyze the clinical characteristics of living-related kidney transplantation (LRKT).
From January, 2004 to December, 2008, 175 LRKT were performed including 63 cases (36%) of parent-child relations and 49 cases (28%) of sibling relations between the recipients and donors. Out of 175 donors, 52 were 50 years old or above, 4 had microscopic hematuria (including 2 with also hypertension), 2 had kidney stone, and 2 had high body mass index (BMI). Zero-point graft biopsy was performed in 59 donors, and abnormalities were found in 15 of them. The recipients were at the age of 33-/+10.5 years, and the primary diseases are mainly dominant glomerular nephritis (72.6%, 127/175), and with a few cases of diabetes (4%, 7/175) and hypertensive nephropathy (4%, 7/175).
Serum creatinine of the donors was 102-/+22.5 micromol/L at 7 days postoperatively, and 92-/+19.1 micromol/L at one month. One recipient died of severe pulmonary infection. Two recipients underwent graft nephrectomy due to anastomotic stenosis with concomitant acute graft rejection and renal arterial embolism. The one-year survival rates of the patients and grafts were 99.3% and 98.2%, respectively. The incident rates of accelerated rejection and acute rejection were 1.1% and 14.9%, respectively. Other complications included impaired liver function (22.3%), infection (9.7%) and leucopenia (4.6%). The renal arterial stenosis occurred in 2.3% (4/175) of the recipients.
The recipients of living-related and cadaveric kidney transplant have different primary kidney disease spectrums. Differential diagnosis and treatment of acute rejection and renal artery or anastomotic stenosis can be of vital importance. Marginal donor kidneys with appropriate inclusion criteria can be safely used for transplantation. With good short-term patient and graft survival, LRKT needs further study to evaluate its long-term effect.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 09/2009; 29(9):1878-81.
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ABSTRACT: To investigate the characteristics of post-transplantation diabetes mellitus and analyze its risk factors.
Extensive survey was carried out to understand the characteristics of posttransplantation diabetes mellitus in patients who received kidney grafting from February 1984 to December 2006.
Three hundred forty-four post-transplantation diabetes mellitus patients from 1872 ones after kidney grafting were found from February 1984 to December 2006. The prevalence of new onset posttransplant diabetes mellitus and impaired fasting glucose in kidney allograft recipients were 18.4% and 12.7% respectively, being significantly higher than that in general population and other inpatients. The options of immunosuppressants were significantly associated with the prevalence of post-transplantation diabetes mellitus. By multivariate logistic regression analysis, the baseline characteristics of the post transplantation diabetes mellitus patients were significantly associated with increased age (OR: 1.309, P = 0.049), elevated level of the triglyceride ( OR: 1.311, P = 0.005), treatment with tacrolimus (FK506) (OR: 1.522, P = 0.008), and large dose of intravenous pulsed prednisolone (OR: 1.239, P = 0.011), as compared with patients without post-transplantation diabetes mellitus. Besides, the number of patients with at least one acute rejection episode was significantly greater in the post-transplantation diabetic patients. Mycophenolate mofetil (OR: 0.716, P = 0.028) and diltiazem (OR: 0.737, P = 0.015) were associated with lower risk of post-transplantation diabetes mellitus.
High prevalence of abnormal glucose metabolism in renal allograft recipients during hospitalization was observed. Many risk factors contributed to the development of post transplantation diabetes mellitus.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 07/2009; 48(7):547-51.
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ABSTRACT: Ten triterpenoid glycosides, yemuoside YM(26-35) (1-9 and 12), were isolated from a traditional Chinese medicine known as "Ye Mu Gua" (Stauntonia chinensis DC.) along with two known ones, kalopanax saponin C (10) and sieboldianoside A (11). Their structures, as elucidated by spectroscopic analyses and chemical methods, were either penta-saccharidic or hexa-saccharidic bidesmoside triterpenoid glycosides. To help explain the clinical applications of "Ye Mu Gua" for its anti-inflammatory effects, the inhibitory activity on the release of inflammatory mediators (nitric oxide, TNF-alpha and IL-6) of 1-12 and the related aglycone, hederagenin (13), was evaluated in vitro. It was found that compound 13, but not 1-12, exhibited significant inhibitory activity. The abundant triterpenoid glycosides in "Ye Mu Gua" might therefore be transformed into their respective aglycones, and thus inhibit the release of inflammatory factors in vivo. This could then account for the clinical value of "Ye Mu Gua" as regards anti-inflammatory effects. This proposed explanation of how "Ye Mu Gua" may have an effect is similar to the concept of prodrugs for chemical drugs which could be extended to some traditional medicines. That is, the major components might be biologically active not directly, but via biochemical transformation in vivo. Hence, we propose a "traditional medicine's prodrug characteristic" concept.
Phytochemistry 06/2009; 70(6):795-806. · 3.35 Impact Factor
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ABSTRACT: To explore methods of clinical diagnosis and treatment of BK virus (BKV) infection in renal transplant recipients.
Urine samples were collected from 227 renal transplant recipients who had undergone renal transplantation at most 48 months to detect the decoy cells. Samples of urine and peripheral blood (BP) were collected to undergo real-time PCR to detect the BKV DNA. Part of the renal-recipients received graft biopsy. The recipients with BKV viruria or viremia were divided into 2 groups: intervention group and control group. The 51 patients of the intervention group had the doses of cyclosporine A (CsA) reduced (n=19), had their doses of FK506 reduced (n=22), or underwent replacement of FK506 with CsA (n=10). And other 29 patients in the control group did not receive any intervention. Acute rejection was intensively monitored. The amount of decoy cells, and BKV load in the urine and PB samples were measured again after 3 months.
The positive rates of urine decoy cell, BKV viruria, and viremia in all patients were 33.0%, 33.5%, and 15.4% respectively. In the intervention group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB before intervention were 5.0/10 HP, 1.50 x 10(4) copies/ml and 0 copy/ml respectively ; and the median levels of decoy cell in urine, and of BKV DNA in urine and PB were all 0 after intervention, all significantly lower than those before intervention (all P < 0.01). In the control group, the median levels of decoy cells in urine, and of BKV DNA in urine and PB were 6.0 /10 HP, 0.79 x 10(4) copies/ml, and 0 copy/ml respectively before observation, and the median level of BKV load in urine ofter observation was 2.21 x 10(4) copies/m, significantly higher than that before observation (P < 0.01), however, the median levels of decoy cells in urine and of BKV DNA in PB were 5.0 /10 HP and 0 copy/ml respectively, not significantly different from those before observation ( both P > 0.05). The differences between the levels of urine decoy cells, urine BKV DNA level and blood BKV DNA level of the intervention group were all significantly greater than those of the control group (Z = -2.749, -5.089, -1.996; P = 0.006, 0.000, 0.046 respectively). And during the intervention no acute rejection was observed. Four cases of BKVAN were diagnosed. Treatment of immunosuppression reduction showed effectiveness in 4 BKVAN recipients. The levels of decoy cells in urine, and BKV load in urine and in PB samples were all decreased. The graft functions were improved.
Urine cytology is very convenient, useful and sensitive for the evaluation and followup of renal transplant patients, and can reflect renal histological presentation indirectly. Also BKV DNA detection in the urine and peripheral blood is important to screen the evidence of BK reaction in order to prevent irreversible graft damage of BKVAN. The treatment of immunosuppressant reduction and replacement of FK506 with CsA are effective in BKV infection recipients at the early stage.
Zhonghua yi xue za zhi 08/2008; 88(26):1824-8.
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ABSTRACT: To investigate the protective effects of estrogen on the mitochondria in human umbilical vascular endothelial cells (HUVECs).
HUVECs were exposed to H2O2 at 250 micromol/L for 4 h with or without pretreatment with 17-estradiol (E2) and ICI182780. Complex IV activity of the cells was measured with chromometry, and 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular adenosine triphosphate (ATP) level was quantified with a luciferin- and luciferase-based assay.
Compared to the blank control group, H2O2 caused a decrease in complex IV activity, intracellular ATP level, and the cell viability, but elevated intracellular ROS. E2 pretreatment of cells significantly attenuated these effects of H2O2 exposure. ICI182780 administered prior to E2 pretreatment antagonized the protective effects of E2 against H2O2 exposure.
E2 offers mitochondrial protective effects on HUVECs, which is mediated by the estrogen receptors.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 08/2008; 28(7):1154-6.
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Gang Huang,
Li-Zhong Chen,
Chang-Xi Wang,
Ji-Guang Fei,
Jiang Qiu,
Jun Li,
Su-Xiong Deng, Guo-Dong Chen,
Wen-Tao Zeng,
Qian Fu,
Yu-Lian Ji
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ABSTRACT: To explore the clinical diagnosis of BK virus (BKV) infection in renal transplant recipients.
Urine and peripheral blood samples were taken from 234 renal transplant recipients for BKV detection with cytological test and real-time PCR.
The occurrence rate of urine decoy cells, BKV viruria and viremia in these patients was 33.3 %, 33.3% and 16.2%, respectively, and the median level of urine decoy cells was 6/10 HPF, with the median level of urine and peripheral blood BKV of 7.62 x 10(3) copy/ml and 7.61 x 10(3) copy/ml, respectively. The positivity rate of BKV in the urine samples were significantly higher than that in peripheral blood samples (P=0.000). The amount of decoy cells was related to BKV load in the urine samples (gamma=0.59, P=0.000), but the BKV load in the urine samples was not related to that in peripheral blood samples (P=0.14).
Renal transplantation is associated with increased BKV shedding, indicating the necessity of BKV monitoring in renal transplant recipients with urine cytology, which is convenient and sensitive and indicates renal histological changes indirectly. Urine and peripheral blood BKV DNA detection is of value in identifying BKV activation to prevent irreversible graft damage of BKV-associated nephropathy.
Nan fang yi ke da xue xue bao = Journal of Southern Medical University 11/2007; 27(10):1593-6.
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ABSTRACT: To explore the roles of CD4+ CD25+ and CD8+ CD28- T regulatory cells in spontaneous tolerance of inbred rats orthotopic liver Transplantation.
The orthotopic liver transplantation models of spontaneous tolerance were established between BN (donor) and LEW (recipient) inbred rats whose survival time was more than 120 days, The expression of CD8+ CD28- T and CD4+ CD25+ T cells in PBMC and spleen were determined by flow cytometry. CD8+ CD28- T and CD4+ CD25+ T cells were sorted by immunomagnetic beads. The expressions of CD25, CD28, CD152 and CD45RO on CD8+ CD28- T and CD4+ CD25+ T regulatory cells were also determined by flow cytometry.
Compared with control groups, the proportion of CD8+ CD28- T regulatory cells in spontaneous models was significantly increased in peripheral blood mononuclear cells (PBMC) and spleen [PBMC (30.2+/-5.8)% vs (16.4+/-6.1)%; Spleen (23.7+/-7.2)% vs(13.4+/-5.5)% P<0.01]. CD4+ CD25+ T regulatory cells had no change; CD11b was expressed on CD8+ CD28- T regulatory cells in both control groups and tolerance groups, and CD25, CD152 (CTL-4) were not expressed on CD8+ CD28- T regulatory cells. The expression of CD45RO on CD8+ CD28- T regulatory cells was 76.1% in control groups and more than 90% in tolerance groups; CD11b, CD152 (CTL-4) and CD45RO were expressed on CD4+ CD25+ T regulatory cells in both control groups and tolerance groups.
The roles of CD8+ CD28- T cells were more important than CD4+ CD25+ T cells in spontaneous tolerance of rat liver transplantation. the different expressions of CD152 showed the functions of CD8+ CD28- and CD4+ CD25+ T cells were different. The different expressions of CD45RO suggested CD8+ CD28- T regulatory cells was changed before and after liver transplantation.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 06/2006; 38(3):266-70.
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ABSTRACT: To investigate the effects of granulocyte colony-stimulating factor (G-CSF)-mobilized autologous bone marrow stem cells on the liver regeneration of partial liver transplant.
A 50% partial liver transplantation model as established by transplanting parts of the liver of female rats to the male rats with the equal weights that had had parts of their livers resected. Then the transplanted male rats were randomly divided into 3 equal groups: G-CSF + PLTx group that was injected hypodermically with recombinant human G-CSF (rhG-CSF) daily for 5 days and then underwent liver resection and 50% partial liver transplantation (PLTx); PLTx + G-CSF group that underwent PLTx and 3 hours after the transplantation received injection of rhG-CSF daily for 5 days, and PLTx control group that underwent PLTx and 3 hours later received injection of normal saline daily for 5 days. One, 3, 5, 7, and 14 days after the PLTx blood samples and livers were collected from 6 rats from each group, and one hour before the liver was taken bromodeoxyuridine (BrdU) was injected intraperitoneally to be integrated into the synthesis of DNA in the liver cells. Immunohistochemistry was used to detect the CD34 and BrdU-positive cells. In situ hybridization was used to detect the sry (sex-determining region) gene so as to determine the origin of the proliferating cells in the transplanted liver.
The 14-day survival rate of the G-CSF + PLTx group was 90%, significantly higher than those of the G-CSF + PLTx (60%) and PLTx group (50%) (both P < 0.05) with a significant difference between the latter 2 groups too (P < 0.05). The mitosis index of liver cells 3 days after the transplantation of the PLTx + G-CSF group was 30% +/- 5%, significantly higher than those of the G-CSF + PLTx group (24% +/- 7%) and PLTx group (24% +/- 6%) (both P < 0.05) without a significant difference between the latter 2 groups. The rate of BrdU-positive cells of the PLTx + G-CSF group was 42% +/- 6%, significantly higher than those of the G-CSF + PLTx group (38% +/- 4%) and PLTx group (34% +/- 8%) (both P < 0.05). The transplantation the mitosis index and rate of BrdU-positive cells decreased since the 7th days after transplantation in all 3 groups, however, with the same relationship among them. The numbers of CD34(+) cell around the portal area of the 2 G-CSF groups increased since the 3rd day after transplantation in comparison with the PLTx group, was the highest on the 3rd day for the G-CSF + PLTx group, and continued to increase in the PLTx + G-CSF group. Since the 3rd day after transplantation, sry-positive cells were seen in the hepatic sinusoid and portal area in the 2 G-CSF groups, and were rarely seen in the PLTx group.
G-CSF treatment after 50% PLTx significantly promotes liver regeneration and ameliorates the liver damage, thus raising the survival rate.
Zhonghua yi xue za zhi 01/2006; 85(47):3342-5.
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ABSTRACT: To explore the role of stem cell mobilization on regeneration of partially grafted livers.
Rats models with cross-sex 50% PLTx (partial liver transplantation) were established. The rats were divided into three groups: PLTx, WLTx (whole liver transplantation) and sham operation groups. Bone marrow and liver samples were collected on days 1, 3, 5, 7 postoperatively (each n = 6). The quantitative variations of the cells with stem cell markers in the bone marrow, including beta2m-/Thy-1.1+, CD45+/CD34+, Flt2/3+ and c-kit+ markers, were detected using flow cytometry. Sry gene positive cells in donor livers were detected by fluorescent in situ hybridization (FISH), and the expressions of CD34, c-kit and Thy-1.1 were detected by immunohistochemistry technique.
Compared with the WLTx and sham operation groups, beta2m-/Thy-1.1+, CD45+/CD34+ cells in bone marrows in the PLTx group increased on the first postoperative day and decreased on the following days. The CD34, c-kit and Thy-1.1 positive cells detected in portal tract areas peaked during the 3-5 postoperative days. CD34+/CD45+ positive cells could be detected. The expressions of CD34, c-kit and Thy-1.1 positive cells were rare in the WLTx and sham operation groups. Sry+ cells could be detected in portal tract areas and few Sry+/CD34+ and Sry+/Thy-1.1+cells were detected.
In the PLTx group, the stem cells in the bone marrow were mobilized and stem cells in the liver were activated.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 12/2005; 13(11):839-43.
