Farnesoid X receptor up-regulates thyrotropin embryonic factor and at-tenuates pathological injury of Con A-induced hepatitis / 中国病理生理杂志

[ABSTRACT]AIM:ToobservehowfarnesoidXreceptor(FXR)functionedinconcanavalinA(ConA)-induced hepatitis (CIH) and the regulation of FXR-thyrotropin embryonic factor (TEF) pathway.METHODS:C57BL/6 mice were injected with Con A to induce hepatitis .The expression of FXR and TEF in the liver specimens was determined by qRT-PCR and Western blotting .The concentrations of serum ALT/AST and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the blood samples were tested after Con A injection .RESULTS:FXR was down-regulated in CIH mice .TEF was up-regula-ted when FXR was activated by chenodeoxycholic acid (CDCA).Activation of FXR reduced the levels of aminotransferases and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the CIH mice induced by Con A injection .CONCLUSION:FXR activation attenuates CIH mouse liver injury and reduces inflammatory cytokines .FXR activation results in TEF up-regu-lation.The FXR-TEF pathway may play a protective role in autoimmune hepatitis .

Effect of ischemia preconditioning on renal ischemia/reperfusion injury in rats

To study the effect of ischemia preconditioning (IP) on renal ischemia/reperfusion (I/R)-associated functional injury and expression of renal adhesion molecules in rats.

The ischemia preconditioning plan adopted in this experiment involved renal warm ischemia for 6 min. and blood flow for 4 min., repeated four times. The Wistar rat kidneys used for warm ischemia preconditioning were subjected to 60 min of renal warm ischemia followed by reperfusion. The rat kidneys with ischemia/reperfusion were compared with the ischemia preconditioning group to observe rat renal function and changes in the expression of renal adhesion molecules ICAM-1, P--Selectin, and E-Selectin.

The expression of rat renal adhesion molecules (ICAM-1, P-Selectin, and E-Selectin) with ischemia preconditioning was significantly lower than that of the ischemia/reperfusion group. Serum creatinine was significantly lower than that in the ischemia/reperfusion group after 48 hours.

Ischemia preconditioning has a protective effect on renal function. Reduced expression of renal adhesion molecules is likely a mechanism involved in the observed protection. .

Repressing malic enzyme 1 redirects glucose metabolism, unbalances the redox state, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines / 癌症

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

Clinical analysis of 6 cases of systemic lupus erythematosus complicated by transverse myelitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the clinical features and therapeutic approach of systemic lupus erythematosus (SLE) complicated by transverse myelitis (TM).</p><p><b>METHODS</b>The clinical characteristics, laboratory examinations, treatment and prognosis of 6 SLE cases with TM were retrospectively analyzed with review of the literatures.</p><p><b>RESULTS</b>The 6 patients consisted of 5 females and 1 male aged 14 to 36 years (mean 23 years). The mean duration from symptom onset of SLE to TM was 8 months (1 to 13 months). All the patients had lower limb hypodynamia, and 3 of them developed upper limb hypodynamia. MRI scanning of the spine identified lesions in the cervical spinal cord in 2 cases, thoracic lesions in 3 cases, and multiple involvement of the cervical, thoracic and lumbar cord in 1 case. Examination of the cerebrospinal fluid yielded no specific findings except for leukocytosis in 1 case and hypoglycemia in another. Five cases were treated with high-dose MP+CTX, and the other case was treated with MP (80 mg/day)+CTX. Five patients responded favorably to the treatment, while the other showed no obvious improvement.</p><p><b>CONCLUSION</b>TM is a rare complication of SLE affecting mostly young patients and occurring in the early stage of the disease. Early diagnosis and aggressive treatment might improve the prognosis.</p>

Clinical analysis of the relevance between adult-onset Still's disease and macrophage activation syndrome / 中华风湿病学杂志

Objective To explore the relationship between Adult-onset Still's disease (AOSD) and macrophage activation syndrome (MAS). Methods A total of 78 patients with AOSD who had completed medical information were included in this study. Eleven patients who were diagnosed as rheumatic disease associated hemophagocytic syndrome among 26 patients who had hemophagocytic syndrome with histological evidence consisted of the MAS group. Clinical and laboratory data were analyzed in 78 patients with AOSD and 11 patients with MAS. Results Among 78 cases of AOSD, 9 patients (12%) could be diagnosed as MAS but didn't have hemophagocytic histological evidence. In the 11 MAS cases with hemophagocytic phenomenon, 6 patients fulfilled the diagnostic criteria of AOSD, 2 cases with panniculitis, 1 case with SLE, 1 case of dermatomyositis and 1 case of systemic vasculitis. Logistic analysis showed that splenomegaly (OR =2.13, 95%CI=1.11-3.42), leukopenia (OR=3.57, 95%CI=2.30～4.86), anaemia (OR=0.85, 95%CI=1.03～2.76), thrombocytopenia (OR=2.98, 95%CI=1.17-4.30) and hypertriglyceridemia (OR=1.66, 95%CI=1.02～2.74) were associated with development of MAS in AOSD. Conclusion The development of MAS in AOSD patient is frequent and hemophagocytic histological evidence could be found in severe cases. When splenomegaly and hypocytomsis present in AOSD patients, bone marrow examination should be done and the level of triglyceride and fibrinogen and activity of NK cells should be measured for early diagnosis.

A study of prognosis in adult onset Still's disease patients / 中华风湿病学杂志

Objective To investigate the potential clinical factors associated with the prognosis and relapse of adult onset Still's disease(AOSD).Methods The factors possibly influencing the prognosis and relapse of AOSD were analyzed by logistic regression and COX regression in the cohort study.Ninety-six con- secutive inpatients of AOSD diagnosed based on Yamaguchi criteria in the hospital from March 1996 to September 2004 were included in the study.Results Nine cases(9.4%)were lost during the follow-up. Eleven patients(12.6%)were diagnosed as other diseases(5 with other rheumatic diseases,4 with tumor and 2 with infections)in the 87 follow-up cases.In 76 cases,3 patients(3.9%)died and 33 patients(43.4%) got remission over one year after treatment.Splenomegaly(OR=3.14,95%CI=1.01～9.74)and treated with methotrexate(OR=0.22,95%CI=0.07～0.67)were associated with the prognosis from the logistic regression analysis of the 76 cases.The serum ferritin(RR=I.05,95%CI=1.01～1.08)and treated with methotrexate (RR=0.13,95%CI=0.02～0.76)were associated with relapse from the COX regression analysis of the 61 remis- sion cases.Conclusion We need to be very cautious in the follow-up of AOSD patients because some of them may change to other diseases.Methotrexate may be an importent therapy of AOSD not only in improve- ment the prognosis but also in reduction of relapse.

Expression of B lymphocyte stimulator in peripheral blood mononuclear cells in individuals with systemic lupus erythematosus and the role of interferon-? on it's expression / 中华风湿病学杂志

Objective To determine the expression of membrane-bound B lymphocyte stimulator (BLyS) protein and its mRNA in vitro of peripheral blood mononuclear cells (PBMCs) from individuals with systemic lupus erythematosus (SLE),and to investigate the role of interferon-?(IFN-?) on the expression of BLyS.Methods PBMCs were obtained from 25 SLE patients (mean age of 31+14) and 20 healthy volunteers (mean age of 28?10).They were randomized into IFN-?(5 ng/ml) group and control group.PBMCs were col- lected at 0,6,12 and 24 h for BLyS mRNA assessment using semi-quantitative reverse transcription-PCR (RT-PCR).PBMCs were also collected at 72 h for membrane-bound BLyS protein detection using flow cy- tometry (FACS) and direct immunofluorescence.Results①The expression of BLyS mRNA and membrane- bound protein in PBMCs was significantly higher in individuals with SLE compared with healthy controls (P＜0.05);②IFN-?enhanced BLyS mRNA expression in PBMCs in both healthy controls and SLE patients,with the greatest effect at 6 h (stimulated vs unstimulated,0.42?0.19 vs 0.25?0.14,P＜0.01;0.59?0.28 vs 0.44?0.21,P＜0.01 );③IFN-?also increased the expression of membrane-bound BLyS protein in both healthy con- trols and individuals with SLE (FACs,mean fluorescence intensity,4.5+3.0 vs 3.7~2.6,P

Expression of B lymphocyte stimulator in peripheral blood mononuclear cells in individuals with SLE and effect of dexamethasone on its expression / 中国病理生理杂志

AIM: To determine the expression of membrane-bound B lymphocyte stimulator((BLyS)) and its mRNA in peripheral blood mononuclear cells(PBMCs) from individuals with systemic lupus erythematosus(SLE),and to investigate the effect of dexamethasone on(BLyS) expression.METHODS: PBMCs were obtained from 25 individuals with SLE(mean age of 31.40?14.23) and 20 female healthy volunteers(mean age of 28.20?10.36).They were randomized into dexamethasone((1 ?mol/L)) group and media group.PBMCs were gathered at 0,6,12 and 24 h for(BLyS) mRNA assessment using reverse transcription-PCR(RT-PCR).PBMCs were also collected at 72 h for membrane-bound(BLyS) protein detection using flow cytometry(FACS) and direct immunofluorescence.RESULTS:(1) The expression of(BLyS) mRNA and membrane-bound protein were significantly higher in PBMCs from individuals with SLE than that in PBMCs from healthy controls(0.40?0.18 vs 0.27?0.20,P