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Biomedical subjects

Z K Chen

Publications and source records attributed to Z K Chen.

At least 19 recordsLinked to original sources
PubMed2006

Induction of accommodation model by combined RNA interference targeting 1,3-galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.

OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial cells and human serum in vitro after successfully silencing the expression of porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference (RNAi), and to investigate the possibility of inducing accommodation in vitro by stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal expression patterns on a pig endothelial cell immortalized line (PED) was achieved by serial doses of small interfering RNA (siRNA) targeting porcinc alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was observed by 51Cr release and antibody/complement binding assays. RESULTS: With combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited complement-mediated cytotoxicity, which showed a better protective effect than using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS) stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA expression of the protective gene HO-1 was significantly up-regulated after treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low-dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of alpha-Gal expression played an important role in the induction of accommodation.

Animals↗
PubMed2006

Antisense ERK1/2 oligodeoxynucleotide gene therapy attenuates graft arteriosclerosis of aortic transplant in a rat model.

UNLABELLED: Chronic rejection is a major cause of transplant loss that is effected by the extracellular signal-regulated kinases (ERK) pathway. This study investigated the effects of antisense ERK1/2 oligodeoxynucleotide(ODN) gene therapy on chronic rejection. METHODS: Lewis (RT1(1)) rats served as recipients of Brown-Norway (BN, RT1n) grafts. The BN rat abdominal aortas were harvested and orthotopically grafted into Lewis rats. The recipients were divided into three groups: (1) control group (n = 9), (2) random ODN transfer group (n = 10), and (3) antisense ODN transfer group (n = 10). At day 60 after transplantation, the recipients were sacrificed; the grafted aortas were evaluated histologically and immunohistochemically. ERK1/2 protein expression in the grafts was determined using Western Blot assays. Serum levels of slCAM-1 were detected by ELISA. RESULTS: In the control group and random ODN transfer group, we observed a remarkable degree of intimal hyperplasia and inflammatory cell infiltration, including macrophages and T cells. Compared with the control group, antisense ERK1/2 ODN gene therapy resulted in a significant reduction in neointimal proliferation (P < .01), inhibition of ERK1/2 protein expression (P < .01), decreased graft infiltration with CD4+ T lymphocytes (P < .01), CD8+ T lymphocytes(P < .05), and ED-1 macrophages (P < .01) with decreased serum levels of sICAM-1 (P < .05). We obtained a negative correlation between ERK1/2 expression and immune cell infiltration or ICAM-1 level. CONCLUSIONS: Antisense ERK1/2 gene therapy can attenuate graft arteriosclerosis so as to protect aortic allografts. The protection seemed to correlate with inhibition of inflammatory infiltration, implying that the ERK1/2 signal transduction pathway plays an important role in the process of chronic vascular rejection.

Animals↗
PubMed2005

Inhibition of MD-1 expression by immunosuppressants or antisense oligodeoxynucleotides on skin allograft survival in mice.

AIM: The aim of this study was to investigate the effects of inhibition of MD-1 expression using nonspecific immunosuppressants and specific antisense oligodeoxynucleotides (AS-ODNs) treatment on skin allograft survival in mice. METHODS: C57BL/6 to Balb/c skin allograft model was used in all groups, followed by Cyclosporine (CsA), Tacrolimus (FK506), Mycophenolate Mofetil (MMF), and Sirolimus (SRL) intraperitaneally, as well as AS-ODNs intravenously. Recipients were humanely killed at 11 days after transplantation. MD-1 expression was determined using flow cytometric analysis (FACS). AlamarBlue was used to evaluate proliferation. And serum levels of interleukin (IL)-2 and IL-10 were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with saline controls, the mean survival times (MST) of skin allografts in all of the immunosuppressants and AS-ODNs treated groups were significantly prolonged (P < .05). CsA, MMF, and AS-ODNs inhibited MD-1 expression and lymphocyte proliferation, as well as decreased serum level of IL-2 and increased that of IL-10; FK506, treatment showed all the effects mentioned above but up-regulated the IL-10 level; SRL had no significant influence on either MD-1 expression or IL-2 and IL-10 level, although it equally suppressed the proliferation (P < .05 vs controls). The negative correlation between MD-1 expression and lymphocyte proliferation or IL-2 level was significant, as was the positive correlation between it and IL-10 level (P < .01). CONCLUSIONS: CsA, FK506, MMF, and AS-ODNs can efficiently inhibit MD-1 expression. The effects of the immunosuppressants are seemingly associated with the down-regulation of the IL-2 serum level. MD-1 was theorized to play an important role in rejection promotion, although the precise relationship between it and allograft survival still remains ambiguous.

Animals↗
PubMed2005

Magnesium supplementation prevents chronic cyclosporine nephrotoxicity via adjusting nitric oxide synthase activity.

INTRODUCTION: Nitric oxide synthase (NOS) is a protective factor for chronic cyclosporine nephrotoxicity by virtue of adjusting the production of nitric oxide (NO). The aim of this study was to explore the role of NOS in the effect of magnesium supplementation to prevent chronic cyclosporine nephrotoxicity. METHODS: Rats maintained on a low-salt diet were divided into three groups: normal controls, cyclosporine group (CsA 15 mg x kg(-1) x d(-1) subcutaneously) and CsA + Mg2+ group (CsA subcutaneously and dietary supplementation with 0.6% Mg enriched by MgCl2). On day 28, plasma Mg2+, plasma creatinine, NOS activity, and NO content in renal tissue were examined. The renal expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in kidneys was determined by an immunohistochemistry technique. The lesions of chronic cyclosporine nephrotoxicity were identified by HE and PAS stains as well as electron microscope. RESULTS: After 28 days of CsA administration, characteristic histological lesions of chronic cyclosporine nephotoxicity were observed, including arteriolopathy, tubular atrophy and interstitial fibrosis. Giant mitochondria and microcalcifications were observed by electron microscopy. Simultaneously, constitutive nitric oxide synthase (cNOS) activity in kidneys was increased, but NO content did not increase correspondingly (P < .05) compared with normal controls. Dietary supplementation with Mg2+ ameliorated the CsA-induced histological lesions. cNOS activity was decreased to normal levels and NOS was increased (P < .05) compared with animals that only received CsA. CsA and magnesium supplementation did not change iNOS activity. CONCLUSIONS: Dietary supplementation with Mg2+ seems to improve renal function and almost abolish CsA-induced histological lesions via altering the abnormal activation of cNOS in this model.

Animals↗
PubMed2004

Hand-assisted transperitoneal laparoscopic living donor nephrectomy.

OBJECTIVE: We introduced and evaluated the advantages and disadvantages of the hand-assisted transperitoneal laparoscopic technique for living donor nephrectomy. MATERIALS AND METHODS: In December 2001, we started using the technique of hand-assisted transperitoneal laparoscopic living donor nephrectomy (HLDN) in 10 cases. The procedure utilizes a hand-assisted device to increase safety and control of the laparoscopic technique. RESULTS: Only left nephrectomy was performed. The mean total operating and the warm ischemia times were 130 minutes and 3.0 minutes, respectively. Average lengths of renal artery and vein were 1.95 cm and 2.8 cm, respectively. There were no intraoperative or postoperative complications. CONCLUSIONS: HLDN is an easier procedure than the traditional laparoscopic living donor nephrectomy and can greatly mitigate the learning curve. HLDN has shortened warm ischemia time and operating time. It is also good for trocar placement, prevention of torsion of the kidney, control of potential bleeding at the final stage of vascular stapling, and kidney removal. Therefore, HLDN is a promising method for living donor nephrectomy.

Adult↗
PubMed2004

The survival and value of liver transplantation for liver carcinoma: a single-center experience.

UNLABELLED: Liver transplantation for liver carcinoma with cirrhosis is a treatment still in dispute. The objectives were to summarize the survival and cost of 50 liver transplant cases performed for liver carcinoma over nearly 3 years. METHODS: We performed 138 liver transplants from January 1999 to February 2002. There were 50 cases (36.2%) of liver carcinoma with HBV cirrhosis, which were divided into three stages based on the tumor pathology: Stage 1 cases showed a single mass (< or = 5 cm), 4 cases; Stage 2, a single mass > 5 cm or intrahepatic multiple masses without PV cancer embolus, 32 cases; and Stage 3: tumor invasion of the PV or perihepatic lymph nodes or organs, 14 cases. All patients received three to six courses of chemotherapy postoperatively. RESULTS: All four cases of stage 1 survived > 1 year; one of them is at 3 years with good liver function and tumor free. The mean half-year medical cost was $27.100 +/- 108 in stage 1. The half-year survival and medical costs were 62.5% and $31,500 +/- 260 in stage 2 and 15.0% and $35,500 +/- 134 in stage 3. CONCLUSION: Liver transplantation is an effective treatment for early-stage liver carcinoma, that achieves good medical and economic results, but should be limited to advanced liver cancer.

Analysis of Variance↗
PubMed2004

Prolonged heart allograft survival resulted from donor-specific T-cell sequestering and removal by selective splenectomy in mice.

INTRODUCTION: Selective splenectomy when donor antigen-specific activated T cells are sequestered in the recipient spleen may prolong allograft survival because of removal of all of these T cells. OBJECTIVES: We investigated the effect on cardiac allograft survival in mice by means of removal of activated specific T cells by splenectomy. METHODS: Donor (Balb/c) spleen cells were injected into primed allogeneic recipients (C57BL/6). Selective recipient splenectomy and donor-type cervical heart grafting in Balb/c to C57BL/6 from mice were examined at 0, 24, 48, and 72 hours after donor spleen cell infusion. RESULTS: Control C57BL/6 mice rejected Balb/c heart grafts at 6.86 +/- 0.19 days. Delayed heart grafting plus splenectomy at 24 or 48 hours after donor-type spleen cell infusion significantly prolonged heart allograft survival (24 hours: 15.86 +/- 3.44 days, P < .001; 48 hours: 21.71 +/- 5.22 days, P < .001, respectively). However, 72-hour delayed heart grafting plus splenectomy failed to prevent acute rejection (72 hours: 9.57 +/- 2.51 days, P > .01). Immunohistochemistry showed, at 24 to 48 hours after donor antigen infusion, the recipient spleens characterized by an obvious increase in CD4+ CD8+ T cells in periateriolar lymphoid sheaths, marginal zones, and red pulp compared with the 72-hour group. CONCLUSIONS: Transient accumulation of donor-specific activated T cells in the spleen of recipients provide an opportunity to remove all of these T cells by a surgical procedure. As the largest immune organ the spleen is the main place where T cells are activated and regenerated. At 24 or 48 hours when donor-specific T cells were sequestered in the spleen after donor antigen stimulation, selective recipient splenectomy was able to remove the T cells and prolong was allograft survival. Refinement of this protocol may eventually warrant clinical application.

Animals↗
PubMed2001

Effect of sodium dimercaptopropanesulfonate on antagonism of tetramethylenedisulphotetramine to GABA receptor.

AIM: To study effects of sodium dimercaptopropanesulfonate (DMPS) on the antagonism of tetramethylenedisulphotetramine (TETS) to gamma-aminobutyric acid (GABA) receptor. METHODS: Acute toxicity experiments were conducted to observe the effects of DMPS and TETS on mice. Contents of free amino acids in mouse brain were determined with automatic analyzer for amino acids. Autoradiography was used to observe the [3H]GABA bindings in the rat brain slices under different conditions. RESULTS: After icv and ip DMPS, the number of mice experiencing convulsions reduced from 20 in control group to 4 and 2 respectively in TETS poisoned mice. The content of GABA was altered in DMPS control group and TETS control group compared with DMPS protection group and NS control group [micromol/g: (2.09 +/- 0.05) and (2.67 +/- 0.15) vs (2.40 +/- 0.10 (micromol/g)) and (2.41 +/- 0.21)]; the content of glutamic acid was (12.3 +/- 1.2), (12.0 +/- 0.8), (10.2 +/- 0.6), and (11.8 +/- 1.0) micromol/g in NS control group, DMPS control group, TETS control group, and DMPS protection group, respectively. The OD value of autoradiograms decreased in TETS group compared with buffer control group in cortex, hippocampus, diencephalon, and brainstem [(0.084 +/- 0.008), (0.081 +/- 0.009), (0.094 +/- 0.006) and (0.081 +/- 0.006), vs (0.102 +/- 0.003), (0.109 +/- 0.005), (0.128 +/- 0.007), and (0.125 +/- 0.008), respectively]. OD value was maintained or higher than the normal level in DMPS+TETS group in the four brain areas [(0.116 +/- 0.008), (0.125 +/- 0.011), (0.129 +/- 0.005), and (0.128 +/- 0.010) vs (0.102 +/- 0.003), (0.109 +/- 0.005), (0.128 +/- 0.007), and (0.125 +/- 0.008), respectively]. CONCLUSION: The inhibitory effects of DMPS on the antagonism of TETS to GABA receptor are due to the increase in the GABA binding to its receptors in brain caused by DMPS

Animals↗
PubMed1998

Isolation and characterization of a group of oligopeptides related to oxidized glutathione from the root of Panax ginseng.

Six gamma-glutamyl oligopeptides were isolated for the first time from aqueous methanol extracts of Panax ginseng root by using column chromatography on ion-exchange resin, gel filtration and reverse-phase high-performance liquid chromatography. Their structures had been established with the methods of amino acid analysis, N-terminal, C-terminal determination and double-coupling sequence analysis. They were: P-I (N-gamma-glutamylcystinyl-bis-glycine), P-ll (gamma-glutamylcysteinylglycine disulfide, oxidized glutathione), P-III (N,N'-bis-gamma-glutamylcystinylglycine), P-IV (gamma-glutamylcysteinylglycinamide disulfide), P-V (N-gamma-glutamylglycylcysteine disulfide), P-VI(gammaglutamylarginine); five of them are related to oxidized glutathione. The structures were further confirmed by the chemical synthesis. As far as we know, P-V (N-gamma-glutamylglycylcysteine disulfide) is a new biologically active peptide which exhibits somnogenic effect and is more potent than that of P-II.

Amino Acids↗
PubMed1997

Prolongation of murine vascularized heart allograft survival by recipient-specific anti-major histocompatibility complex class II antibody.

BACKGROUND: Antibodies targeting recipient major histocompatibility complex (MHC) class II molecules have been demonstrated to be effective at prolonging allograft survival. However, antigen-presenting cell depletion would explain this effect and has not been definitively excluded as the mechanism of action of such antibodies. We have studied an anti-MHC class II antibody (OX6) proven to be noncytotoxic in the recipient strain used. METHODS: Antibody was administered the day before, 2 hr before, and the day after grafting. RESULTS: Antibody administration on the day before, 2 hr before, and the day after grafting significantly prolonged vascularized cardiac allograft survival. Importantly, treatment recognizing recipient MHC was effective, whereas a similar regimen recognizing donor MHC was not. CONCLUSIONS: Noncytotoxic recipient MHC class II-specific antibodies modify allograft rejection. Possible mechanisms for this therapeutic effect are discussed.

Animals↗