Objective To study the role of inositol requiring enzyme 1 (IRE1)-mediated endoplasmic reticulum stress on hepatocyte apoptosis of experimental fulminant hepatic failure (FHF).Methods Thirty male depuratory Wistar rats were manufactured to be FHF model by peritoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS),and 30 rats were injected peritoneally with 0.9％ sodium chloride solution as controls.The apoptosis of liver cells was detected by flow cytometry.The protein and mRNA expressions of Caspase-12 and IRE1 in liver tissues were detected by immunohistochemistry and reverse transcriptation-polymerase chain reaction (RT-PCR).The independent samples were compared by Kruskal-Wallis H test.The comparison between two groups at the same time point was done by Mann-Whitney U test.The correlation analysis was done by rank correlation.Results The apoptotic rates of liver cells at 2,4,8 and 12 hours were increased over time in model group (x2 =25.475,P=0.01),which were higher than control group (U=0,P＜0.01).The expressions of Caspase-12 and IRE1 proteins in liver tissues were upregulated in model group,while the expressions were not detected in control group.The expressions of Caspase-12 and IRE1 mRNA in model group were also increased over time and peaked at 8 h,then gradually decreased; the differences among different time points were statistically significant (x2 =23.983,x2 =24.820; both P＜0.01),and all higher than control group (U=0,P＜0.01).IRE1 was positively correlated with both Caspase-12 and hepatocellular apoptotic rate (r=0.733 and 0.715,respectively;both P＜0.01).Caspase-12 was positively correlated with hepatocellular apoptotic rate (r=0.586,P＜0.01).Conclusions IRE1 mediated endoplasmic reticulum stress on hepatocyte apoptosis is closely related to the development of FHF.The earlier intervention on endoplasmic reticulum stress pathway,the more protective effect in liver failure.

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The envelope protein(Env) of lentiviruses such as HIV,SIV,FIV and EIAV is larger than that of other retroviruses.The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus,demonstrating that envelope is crucial for vaccine.We compared Env variation of the four kinds of lentiviruses.Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor,and the relationship of HIV and EIAV was the furthest.EIAV had the shortest Env length and the least number of potential N-linked glycosylation sites(PNGS) as well as glycosylation density compared to various immunodeficiency viruses.However,HIV had the longest Env length and the most PNGS.Moreover,the alignment of HIV and SIV showed that PNGS were primarily distributed within extracellular membrane protein gp120 rather than transmembrane gp41.It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env.There are low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.

Objective To investigate the expression of c-kit and analyze its relationship with proliferating cell nuclear antigen (PCNA) in RCC subtypes and its clinical progression. Methods Expression of c-kit protein was retrospectively studied with immunohistochemistry in paraffin sections from 137 cases of clear renal cell carcinoma (CCRCC), 82 papillary renal cell carcinoma (PRCC), 51 chromophobe renal cell carcinoma (ChRCC). Results The positive rate of c-kit in ChRCC was 94.1%(48/51), it was statistically higher than that in CCRCC (16. 1%, 22/137) and PRCC (28.1 %, 23/82)(P=0. 001 ). In ChRCC, the positive expression of c-kit was related with TNM stages. The positive expression of PCNA was related with the grade in CCRCC and PRCC. But there was no relationship between PCNA expression and grade of ChRCC. It also had the relationship with the metastasis in CCRCC. Conclusions The expression of c-kit in ChRCC is higher than in other subtype of RCC, and associated with tumor local progression. That makes c-kit as a helpful marker to discriminate different subtypes of kidney cancer.

Objective To observe the influence of early intestinal barrier protection in patients with severe acute pancreatitis(SAP). Methods To analyze the therapeutic methods and prognosis of 56 patients with SAP. The patients were randomly divided into the conventional therapy group (A) and the intestinal barrier protection group (B). The APACHE Ⅱ score, Ranson score, Marshall score, CT severity index (CTSI), gastrointestinal functions score (GFS), the ratio of Lactulose to Mannitol (L/M), plasma Endotoxin and Diamine Oxidase (DAO), serum C-reactive protein (CRP) and TNF-α, incidence of pancreatic infection and multiorgan dysfunction syndrome (MODS), and the hospitalization mortality were compared between the two groups. Results On the 7th day after admission, the APACHE Ⅱ score, GFS, L/M, Endotoxin, DAO, CRP and TNF-α were significantly less in group B than in group A (P<0. 05). There was no significant difference in the CTSI (P>0. 05)between the two groups at 2nd week after admission. The incidence of pancreatic infection and MODS in group B were significantly lower than in group A (P<0. 05). The hospitalization mortality was not significantly different (P>0. 05) between the two groups. Conclusion Early intestinal barrier protection in SAP alleviated systemic inflammatory response, and reduced the incidences of pancreatic infection and MODS, thus improved the prognosis.

Objective　To analyze the clinicopathological features of angiolymphoid hyperplasia with eosinophilia (ALHE). Methods　The pathological specimens of 7 cases of ALHE collected in our department from 1950 to 1999 were sectioned, stained and observed. Results　There were 3 pathological characteristics in ALHE: ①massive hyperplasia of capillaries in the dermis; ②the endothelial cells proliferated and swelled, projecting into vascular cavity like tombstones; ③mixed infiltration of lymphocytes and eosinocytes in the vessels. Conclusion　ALHE is a disease with local benign proliferated vessels, whose etiology and pathogenesis is still unknown. It is necessary to grasp the pathological changes of ALHE to distinguish it from other diseases.

This study is to investigate whether naked plasmid DNA can effectively transfect lung cancer related cells and express human kallistatin, an endogenous protein that inhibits angiogenesis and tumor growth, and to explore the biological activity of the low-level expressed kallistatin to lung cancer in vitro and in vivo. The plasmids were delivered with Lipofectamine 2000 to transfect various lung cancer related cells. Kal expression was determined by ELISA. The biological effects of Kal expression on proliferation, migration and apoptosis rate of the cells were examined. In subcutaneous NCI-H446 xenograft model, pKal was injected directly into tumors, the changes of CD34, Ki-67 and E-cadherin expression were detected with immunohistochemical assay, the tumor apoptosis was analyzed with TUNEL assay. Both the endothelial cell and lung cancer cells could express kallistatin after plasmid transfection. The proliferation and migration of human umbilical vein endothelial cells were inhibited, but the apoptosis rate was not affected. The proliferation rates of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited, and their apoptosis rates were enhanced, but different cells behaved differently. In subcutaneous NCI-H446 xenograft model, intratumor injection of pKal inhibited the growth of lung cancer by reducing angiogenesis and proliferation of tumor cells. In conclusion, this study demonstrated the efficacy of plasmid-mediated expression of kallistatin to lung cancer related cells, thus providing a basis for their clinical application in the treatment of lung cancer.
Animals ; Antigens, CD34 ; metabolism ; Apoptosis ; Cadherins ; metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Plasmids ; Serpins ; genetics ; metabolism ; physiology ; Transfection ; Tumor Burden

0.05).Conclusions The higher level of SEB-specific IgM and IgE in AD and eczema indi cates the colonization of Staphylococcus aureus,which participates in the exace rbation of allergic inflammation,is involved in the pathogenesis of AD and ecz ema.

Multidrug resistance (MDR) of cancer cells to anti-tumor drugs remains a major impediment to successful chemotherapy. There has been an increasing interest in the studies of the mechanism and reverse of the MDR. Being a reliable and safe way to reverse MDR, drug delivery systems (DDS) such as micelle, liposome and nanoparticle, represent a promising prospect both in research and application in recent years. On the basis of recent studies, the effect and mechanism of micelles on reversing MDR are reviewed. And it is anticipated that DDS could contribute greatly to reversing MDR in the future.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Drug Delivery Systems ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Micelles ; Nanoparticles

AIMTo study the characteristics of neural information encoding of the epileptic networks involved caudate-putamen(CPu) and the hippocampi induced by tetanization of the right CPu in rats.

METHODSExperiments were performed on 59 SD rats. Acute or chronic tetanization of the right CPu (ATRC or CTRC) (60Hz,0.4-0.6 mA, 2 s) was used to induce rat epilepsy.

RESULTS(1) The bursting or primary unit afterdischarges of single neurons were asymmetric in dual hippocampi induced by the ATRC. (2) Continuous sharp waves were observed in ipsilateral or contralateral CPu induced by the CTRC. The oscillatory network seizures with phase shift appeared between two sharp waves in ipsilateral CPu. The frequency of oscillatory waves was negatively correlated with the time and fluctuated from 70 Hz to 110 Hz, then to 35 Hz, and finally to 30 Hz. (3) In the contralateral side primary network after discharges in the CPu were induced by the CTRC. Therefore, the characteristic primary network afterdischarges could be shifted from the CPu or to the HPC, but amplified. On the other hand, HPC sharp waves could be depressed when the CPu network seizures occurred.

CONCLUSIONThe reestablishment of CPu-hippocampal epileptic networks could be transhemispherically promoted by over-activation of the right CPu network, in which bilateral hippocampal neuronal network and CPu neural network were involved in some particular pathophysiological information encoding.

Animals ; Caudate Nucleus ; metabolism ; Epilepsy ; physiopathology ; Hippocampus ; metabolism ; Male ; Neurons ; metabolism ; Putamen ; metabolism ; Rats ; Rats, Sprague-Dawley