BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.
METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.
RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues.
CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

Objective: Tumor necrosis factor α(TNFα) induced apoptosis is limited by its coactivation of nuclear factor kappa B(NF- κB) -dependent antiapoptosis genes. We examined whether pyrrolidine dithiocarbamate (PDTC) enhance TNFα - induced apoptosis in cultured breast cancer cells and explored the role of NF - κB in TNFα - induced apoptosis. Methods: Human breast cancer cell lines MCF-7 and MDA - MB -435s were treated with TNFα、 PDTC and combination therapy . Induction of apoptosis was detected by TUNEL staining and flow cytometry. NF- κB DNA binding activity was detected using electrophoresis mobility shift assay(EMSA) . Western blots of cytoplasmic lysates were performed to demonstrate IκBα (Inhibitor protein of nuclear factor κB) phosphorylation and degradation. Results:TNFα-induced IκBo phosphorylation and degradation, which was inhibited by PDTC in both cell lines. TNFα-induced apoptosis (TUNEL) increased significantly when both cells were pretreated with PDTC. Flow cytometry also confirmed this. EMSA showed that PDTC continuously inhibited TNFo-induced NF- κB DNA binding activity . Conclusions:PDTC enhances TNFo-induced apoptosis whileinhibiting IκBα phosphorylation and degradation in human breast cancer cells. NF - κB has a protective role on TNFα-induced apoptosis.

Objective: To study the sequential changes of HIF-1α(hypoxia-inducible factor 1 alpha) in experimental spinalcord injury in rats and to analyze its potential effects inSCI.Methods: A static compression model of SCI wasemployed in this study. Expressions of HIF-1α weremeasured with immunohistochemical staining, while flowcytometry was used to determine the apoptotic ratio andbcl-2 expressions.Results: HIF-1α began to increase 1 day after injury,and reached the peak at 3-7 days. Two weeks later, itdeclined significantly. The sequential changes of HIF-1αcoincided well with the alterations of apoptotic ratio andcontents of bel-2.Conclusions: HIF-1α possibly participates in thesecondary ischemic and hypoxic procedures after spinalcord injury, and may mediate the traumatic apoptosis.Further understanding of HIF-1α may provide newtherapeutic regimens for SCI.

Objective:　To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI). 　　Methods:　Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.　　Results:　The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats. 　　Conclusions:　The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

Objective:　To investigate the spatial and temporal profile of neural cell apoptosis following traumatic brain injury (TBI).　　Methods:　In addition to morphological evidence of apoptosis, TUNEL histochemistry assay was used to identify DNA fragmentation in situ at both light and electron microscopic levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis.　　Results:　Using TUNEL method, we detected massive cells with extensive DNA fragmentation in different regions of the brains of rats subjected to experimental traumatic brain injury. Compared with the sham controls, in the injured cortex, the apoptotic cells were detectable for up to 24 h and reached a peak at 1 week after injury. The number of apoptotic cells in the white matter had a significant increase as early as 12 h after injury and peaked at 1 week. The number of apoptotic cells increased in the hippocampus at 72 h, whereas in the thalamus, the peak of apoptotic cells was at 2 weeks after injury. The number of apoptotic cells in most regions returned to sham values 2 months after injury. Gel electrophoresis of DNA extracted from affected areas of the injured brain revealed only internucleosomal fragmentation at 185-bp intervals, a feature originally described in apoptotic cell death. And no DNA ladder was detectable in the cortex and hippocampus contralateral to the injured hemisphere.　　Conclusions:　These data suggest that in addition to the well described necrotic cell death, a temporal course of apoptotic cell death is initiated after brain trauma in selected brain regions.

Objective:　To investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca2+ reperfusion. 　　Methods:　The apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca2+ reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed. 　　Results:　Both the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes (39.73%±4.16%) were higher than the astrocytes (19.64%±4.67%) 24 hours after Ca2+ reperfusion. The TUNEL positive cells were 13.6±1.82 and 21.4±1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca2+ reperfusion.　　Conclusions:　The astrocytes and oligodendrocytes are similar with the development rules on apoptosis and have different susceptiveness to the situation.

Objective: To explore the expression of hypoxia inducible factor-1α (HIF-1~) and the correlation between HIF-1α and apoptosis after traumatic brain injury.Methods: Using experimental traumatic brain injury in the rats, the expression of HIF-1α was studied by immunohisto-chemistry in cerebral tissue, apoptotic cell death was evaluated with TUNEL (transferase-mediated XdUTP nick end labeling ), and double-labeled immunohistochemistry and TUNEL methods were used to investigate the relationship between HIF-1α and apoptosis.Results: There was remarkable difference in the expression of HIF-1α between the experimental groups and the control groups (P ＜ 0.01), in the experimental groups,the expression of HIF-1α at 48 hours was highest; the evidence of apoptotic cell death after experimental traumatic brain injury was found by TUNEL; the apoptotic percentage increased or decreased according to the changes of the positive expression of HIF-1α (r = 0.99).Conclusions: The results suggest that secondary brain ischemia plays a crucial role in apoptotic cell death after traumatic brain injury; HIF-1α can prompt apoptotic cell death after experimental traumatic brain injury.

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

Background: In clinical studies, the findings on sulfur mustard (SM) toxicity for CD3+CD4+ and CD3+CD8+ T lymphocyte subsets are contradictory. In animal experiments, the effect of SM on the T cell number and proliferation is incompatible and is even the opposite of the results in human studies. In this study, we observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model. Methods: Mice were exposed to SM by subcutaneous injection (20 mg/kg) and were sacrificed 4 h, 24 h, 72 h and 168 h later. Spleen T lymphocyte proliferation was evaluated by3H-TdR. Flow cytometric analysis was used to observe the percentage of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets. The IL-1β, IL-6, IL-10 and TNF-α levels in plasma were assayed using the Luminex method. DNA damage in bone marrow cells was observed with the single cell gel electrophoresis technique (SCGE). Results: SM continuously inhibited the proliferation of lymphocytes for 7 days, and there was a significant rebound of Con A-induced T lymphocyte proliferation only at 24 h. The percentage of CD3+CD4+ and CD3+CD8+ lymphocytes was upregulated, which was accompanied by increased IL-1β and TNF-α and decreased IL-10. The IL-6 level was gradually decreased in the PG group at 4 h. The peak of lymphocytic apoptosis and DNA damage occurred at 24 h and 72 h, respectively. Conclusion: Our results show that SM significantly inhibited T lymphocyte proliferation as well as induced CD3+CD4+ and CD3+CD8+ upregulation. SM intoxication also significantly increased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and inhibited the level of anti-inflammatory cytokine IL-10. Our results may partly be due to the significant SM induced significant apoptosis and necrosis of lymphocytes as well as DNA damage of bone marrow cells. The results provided a favorable evaluation of SM immune toxicity in an animal model.

Anti-osteosarcoma Effects and Mechanisms of 4-o-amino-phenol-4'-demethylepipodophyllotoxin Ether

Nitroxyl spin-labeled derivative of podophyllotoxin induces osteosarcoma cells apoptosis

Glucocorticoid receptor and sequential P53 activation by dexamethasone mediates apoptosis and cell cycle arrest of osteoblastic MC3T3-E1 cells

Objective:To study the killing effect of different doses of preoperative iodine 131 therapy on thyroid cancer cells and its effect on salivary gland function.Methods:Patients diagnosed with thyroid cancer in our hospital from May 2013 to June 2014 were enrolled for study, given preoperative iodine 131 therapy and randomly divided into control group, low dose group, middle dose group and high dose group. Then cell apoptotic rate, cell cycle, cancer promoting gene and cancer suppressor gene expression in thyroid carcinoma tissue as well as salivary gland function were detected.Results: (1) cancer cell killing effect: compared with control group, cell apoptotic rates and number of cells in G0/G1 phase of low dose group, middle dose group and high dose group increased, number of cells in S and G2/M phase decreased, BRAF, Livin, MCM7 and CDK2 expression decreased, CCNG2 and PTEN expression increased; cell killing effect of middle dose group and high dose group were better than that of low dose group, and cell killing effect of middle dose group and high dose group had no differences; (2) salivary gland function: compared with control group, UI and SR in bilateral parotid and bilateral submandibular glands of low dose group, middle dose group and high dose group decreased; salivary gland damage effect of low dose group and middle dose group were weaker than that of high dose group, and salivary gland damage effect of low dose group and middle dose group had no differences.Conclusion:Middle dose of iodine 131 can take the killing effect on cancer cells and the protective effect on salivary glands into account; it’s an ideal dosage for preoperative iodine 131 internal radiation therapy of thyroid cancer patients.

Objective:To study the application value of SIB-CR combined with conventional chemotherapy for advanced central type of non-small cell lung cancer.Methods:60 patients with advanced central type of non-small cell lung cancer were randomly divided into two groups, SIB-CR group received simultaneous integrated boost conformal radiotherapy combined with chemotherapy, and conventional radiotherapy group received conventional radiotherapy combined with chemotherapy. Then cell apoptosis, protein contents of anti-apoptotic molecules and pro-apoptotic molecules in lung cancer tissue as well as lung cancer vitality indicators in serum were detected.Results:Compared with conventional radiotherapy group, apoptotic indexes in lung cancer tissue of SIB-CR group significantly increased; Fas and FasL contents were higher while Bcl-2 and Pim-1 contents were lower; serum Cyfra21-1, SCC and TSGF contents of SIB-CR group were lower than those of conventional radiotherapy group.Conclusion:SIB-CR combined with conventional chemotherapy can induce lung cancer cell apoptosis and regulate the expression of pro-apoptotic and anti-apoptotic genes; its killing effect on lung cancer cells is superior to that of conventional radiotherapy.

Objective:To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods:After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT) assay while apoptosis and cell-cycle phase distribution using lfow cytometry. Results:In 0.01~30.00μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16)μg/mL;the apoptosis rate was increased from 3.4%to 7.0%, 13.8%and 36.3%at concentrations of 0, 0.5, 1.5 and 30μg/mL of evodiamine, respectively;the percentage of cells accumulated in G2/M phase was increased from 17.26%to 98.92%in the cells treated with evodiamine for 24 h in 0.01~30.00μg/mL range of concentrations. Conclusion:Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.