Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Liver Neoplasms ; metabolism ; pathology ; PTEN Phosphohydrolase ; metabolism ; S-Phase Kinase-Associated Proteins ; metabolism ; Thiazolidinediones ; pharmacology

OBJECTIVETo address the hypothesis that hydrogen sulfide (H(2)S) is a functionally significant stimulator in the development of glioblastoma (GBM) and explore the mechanism of stimulation.

METHODSForty adult Sprague-Dawley (SD) rats were given intracerebral injection of rat C6 glioma cell suspension, and an intraperitoneal injection of sodium hydrosulfide (NaHS), an exogenous H(2)S donor. The 40 rats were randomly divided into 4 groups of 10 rats in each: the control group, NaHS group, C6 glioma group (intracerebral implantation of C6 glioma cells) and C6-NaHS group (intracerebral implantation of C6 glioma cells and intraperitoneal injection of NaHS). Food and water were freely available during all phases of the experiment. Physical symptoms were observed and the tumor size was measured. Histological changes were examined by pathology. Immunohistochemical staining was used to analyze the expression of HIF-1α and integrated optical density (IOD) was used to determine the tumor microvessel density (MVD). The H(2)S content in the brain was measured.

RESULTSThe physical symptoms of tumor-bearing rats became more serious after NaHS injection. The H(2)S level in the C6 glioma group was higher than that in the control group [(35.25 ± 1.03) nmol/g vs. (29.12 ± 0.94) nmol/g, P < 0.05], and the highest H(2)S level was found in the C6-NaHS group. The pathological examination showed that the implanted tumors were predominantly spheroid with a distinct border and no capsule could be detected. Neovascular proliferation was also observed. Foci of tumor necrosis, intratumoral hemorrhage, pseudopalisades and tumor cavity were clearly observed. The glioma cells had scant eosinophilic cytoplasm and enlarged hyperchromatic nuclei. All these phenomena were more markedly in the C6-NaHS group compared with that in other three groups. The mean tumor volume was significantly different between the C6 and C6-NaHS rats [(32.0 ± 6.9) mm(3) vs. (67.8 ± 11.9) mm(3), P < 0.001]. Immunohistochemical analysis exhibited that the hypoxia-inducible factor-1alpha (HIF-1α) and CD34 expression were significantly increased after the intraperitoneal injection of NaHS in the C6-NaHS rats (comparing the IOD between C6-NaHS group and C6 group, HIF-1α: 133 962.9 ± 451.4 vs. 38 569.8 ± 408.6, P < 0.001; CD34: 73 368.6 ± 404.8 vs. 14 570.6 ± 748.7, P < 0.001). Moreover, compared with the C6 group, there were higher MVD in the C6-NaHS group [(41.2 ± 7.9)/mm(2) vs. (97.0 ± 10.8)/mm(2), P < 0.001].

CONCLUSIONSH(2)S serves as a stimulator in the development of rat glioblastoma and exogenous H(2)S strongly promotes the tumor growth. The stimulating mechanisms include the increase of HIF-1α expression and neovascular formation. H(2)S may be a significant regulator in the development of tumor.

Animals ; Antigens, CD34 ; metabolism ; Brain ; metabolism ; pathology ; Brain Neoplasms ; metabolism ; pathology ; Glioblastoma ; metabolism ; pathology ; Hydrogen Sulfide ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Injections, Intraperitoneal ; Male ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sulfides ; administration & dosage ; pharmacology ; Tumor Burden

PURPOSE: The aim of this study was to investigate whether propofol could attenuate hypoxia/reoxygenation-induced apoptosis and autophagy in human renal proximal tubular cells (HK-2) by inhibiting JNK activation. MATERIALS AND METHODS: HK-2 cells were treated with or without propofol or JNK inhibitor SP600125 for 1 hour and then subjected to 15 hours of hypoxia and 2 hours of reoxygenation (H/R). Cell viability and LDH release were measured with commercial kits. Cell apoptosis was evaluated by flow cytometry. The expressions of p-JNK, cleaved-caspase-3, Bcl-2, and autophagy markers LC3 and p62 were measured by Western blot or immunofluorescence. RESULTS: HK-2 cells exposed to H/R insult showed higher cell injury (detected by increased LDH release and decreased cell viability), increased cell apoptosis index and expression of cleaved-caspase-3, a decrease in the expression of Bcl-2 accompanied by increased expression of p-JNK and LC3II, and a decrease in expression of p62. All of these alterations were attenuated by propofol treatment. Similar effects were provoked upon treatment with the JNK inhibitor SP600125. Moreover, the protective effects were more obvious with the combination of propofol and SP600125. CONCLUSION: These results suggest that propofol could attenuate hypoxia/reoxygenation induced apoptosis and autophagy in HK-2 cells, probably through inhibiting JNK activation.
Anoxia ; Apoptosis ; Autophagy ; Blotting, Western ; Cell Survival ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Propofol

Objective To investigate the clinical efficacy of endoscopic surgery for extensive osteoradionecrosis (ORN) of skull base in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.Methods Seventeen patients diagnosed as ORN of skull base after radiotherapy for NPC and underwent endoscopic surgery were retrospectively studied with their clinic data.Results Based on the CT and endoscopic examination,all patients had large skull base defects with bone defects averaged 7.02 cm2 (range,3.60-14.19 cm2).Excepting for curetting the sequestra,endoscopic surgery was also used to repair the wound or to protect the internal carotid artery with flap in 12 patients.No bone reconstructions were conducted in all patients with the bone defects of skull base.CT examinations were taken after endoscopic surgery when required.The postoperative follow-up ranged from 8 months to 6 years (average,14 months).Aside from 1 patient with delayed cerebrospinal fluid (CSF),others had no related complications.Conclusions The patients with extensive ORN can be treated with endoscopic surgery to curette the necrotic bone of skull base,and endoscopic reconstruction provides an alternative technique.It may not be necessary to reconstruct the bone defects at skull base,however,the exposed important structures of skull base,such as internal carotid artery,need to repair with soft tissue such as flap.

Objective To observe the T helper 1 and T helper 2(Th1/Th2)balance and possible association to vascular endothelial cells iniury in patients with acute coronary syndromes(ACS).Methods Forty patients with ACS and l 8 patients with stable angina pectoris(SAP)were included in this study.The concentrations of T helper 1/T helper 2 sabsets related cytokines in plasma were evaluated bv ELISA Kits.Cytotoxic activity of peripheral blood mononuclear cells (PBMCs)or PBMCs depleted CD+ T cells against human umbilical vein endothelial cells(HUVECs)were evaluated by Cr51 cytotoxicity assay.Results Concentrations of T helper 1 related cytokines IFN-γ and IL-2 were significantly higher[IFN-γ:(131.2±42.2)ng/L vs.(47.6±20.2)ng/L;IL-2:(83.7 4±21.3)ng/L vs.(46.2±16.7)ng/I.,all P<0.05]while T helper 2 related cytokine IL-10 concentration was significantly lower[(1 6.7 ±4.3)ng/L vs.(27.5±5.5)ng/L.P<0.05 ] in patients with ACS compared to those in SAP patients.Cytotoxic activity of PBMCs against HUVECs in patients with ACS was also significantly higher than that in patients with SAP (28.84%±4.20% vs.20.28%±2.71%,P<0.05).Conclusions In patients with ACS.Th1 related cytokines were significantly upregulated while Th2 related cytokines were significantly downregulated.This imbalante of Th1/Th2 accelerated PBMCs mediated endothelium iniury in patients with ACS.

Zika virus (ZIKV) is a kind of mosquito-borne flavivirus. ZIKV infection initially shows mild symptoms on patients, but will lead to severe neurological complications (such as Guillain-Barré syndrome) in the end. Meanwhile, pregnant women are sensitive to ZIKV, since the viruses may cause microcephaly. In 2015, after the epidemic in Brazil, ZIKV draws the public attention around the world because of its increased virulence and rapid dissemination. However, there is no approved specific anti-ZIKV drugs at present. This review summarizes progress on anti-zika virus drug research and provides prospects in this field.