Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC-MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome , and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.

Association of oxytocin with insulin resistance and highly sensitive C-reactive protein in patients with newly diagnosed type 2 diabetes / 中华内分泌代谢杂志

Objective To detect serum oxytocin and highly sensitive C-reactive protein (hs-CRP) levels in obese and type 2 diabetes mellitus(T2DM) subjects and investigate the relationships between serum oxytocin levels and hs-CRP, glycolipid metabolism, insulin resistance and pancreas β cell function. Methods A total of 176 subjects were enrolled in the study, including 88 patients with newly-diagnosed type 2 diabetes ( T2DM) and 88 subjects with normal glucose tolerance(NGT). NGT and T2DM groups were further divided each into normal weight (NW) and obese(OB) subgroups. Obesity was defined as body mass index(BMI)≥25 kg/ m2 according to the WHO-Western Pacific Region diagnostic criteria (2000). 75g oral glucose tolerance test ( OGTT) was performed in all subjects. Fasting plasma glucose ( FPG), 2 h postprandial plasma glucose (2hPG), fasting insulin ( FINS), 2h postprandial serum insulin(2hINS), HbA1C and lipids were also determined. Insulin resistance and pancreas β-cell function were determined by homeostasis model assessment ( HOMA-IR, HOMA-β). Highly sensitive C-reactive protein(hs-CRP) level was determined by chemiluminescence immunoassay and fasting serum oxytocin level was determined by ELISA. Results Serum oxytocin level was lower in T2DM group than that in NGT group(P<0. 01), while serum hs-CRP level was higher in T2DM group than that in NGT group(P<0. 01). The level of serum oxytocin in subjects with obesity was also lower than that in subjects with NW in both NGT and T2DM groups [7. 16(6. 45-8. 82) vs 7. 98(7. 03-9. 17) ng/ L and 9. 23(8. 16-10. 36) vs 9. 86(8. 77-12. 06) ng/ L, P<0. 05]. The level of serum hs-CRP in subjects with obesity was higher than that in subjects with NW in both NGT and T2DM groups [0. 99(0. 25-1. 97) vs 0. 54(0. 19-0. 91) mg/ L and 3. 47(1. 63-6. 20) vs 1. 65(0. 81-3. 81) mg/ L, P<0. 05]. Serum oxytocin level was negatively correlated with hs-CRP, BMI, WC, WHR, HbA1C , FPG, 2hPG, FINS, 2hINS, total cholesterol, triglycerides, LDL-C and HOMA-IR, while was positively correlated with HOMA-β(P<0. 05). Subjects within the upper serum hs-CRP tertile had lower level of oxytocin when compared to subjects in the middle or lower serum hs-CRP tertiles(P<0. 05 ). Conclusion Serum oxytocin level was decreased in subjects with type 2 diabetes as well as with obesity. Serum oxytocin level was closely correlated with inflammation, glycolipid metabolism, insulin resistance, and pancreas β cell function. It may play an important role in the pathogenesis of obesity and T2DM.

Protective effects of resveratrol on acute lung injury induced by lipopolysaccharide in mices / 中国生化药物杂志

Purpose To investigate the effect of resveratrol on acute lung injury induced by lipopolysaccharide (LPS) in mice.Methods Acute lung injury (ALI) was induced by LPS in mice. The changes of lung airway inspiratory resistance (Ri), expiratory resistance (Re), and dynamic lung compliance (Cdyn) were observed with pulmonary function test apparatus. Brochoalveolar lavage fluid (BALF) was collected, and the concentrations of interleukin 1β (IL-1β)、interleukin 6 (IL-6) and tumor necrosis factory α (TNF-α) were measured by ELISA. The ratio of wet to dry weight was calculated to assess lung edema. Pulmonary vascular permeability was examined with injection Evans blue to judge the destructive extent of alveolar epithelial cell and endothelial. Pathological section was made, and the histopathological change was observed with light microscope.Results Resveratrol can inhibit the elevation of Ri and Re, and the descent of Cdyn. Simultaneously, resveratrol reduced the concentration of IL-1β, IL-6 and TNF-α,as well as the wet to dry weight ratio and the pulmonary vascular permeability significantly. Furthermore, it also could attenuate the lung injury on histopathology.Conclusion The results show that pretreatment with resveratrol has a protective effect on ALI induced by LPS. The ultimate inhibiting and release of inflammatory factors were involved in the mechanism of the effects.

Effects of Ginkgo biloba extract (EGB) on acute myocardial ischemia induced by isoproterenol in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of Ginkgo biloba extract (EGb) in rats with acute myocardial injury induced by isoproterenol (ISO).</p><p><b>METHOD</b>The rats, induced by Isoproterenol (4 mg x kg(-1) x d(-1), 10 d, sc), were divided into groups: sham, model, metoprolol (10 mg x kg(-1) x d(-1), 13 d, ig), EGb (100 mg x kg(-1) x d(-1), 13 d, ig).</p><p><b>RESULT</b>The cardiac parameters of the Model group were compromised significantly in both systolic and diastolic function. Improvement in cardiac function by EGb was significant. In model groups, plasma activities of AST, LDH, CK, HBDH, CKMB and ventricular weight index (LV and RV/BW) were elevated significantly. With the treatment with EGb and metoprolol, the enzymes and ventricular weight index were significantly ameliorated.</p><p><b>CONCLUSION</b>G. biloba extract was beneficial to cardiac performance by improving myocardium enzymes and cardiac function in isoproterenol induced myocardial injury in rats.</p>

The effects of rhIL-11 on hematopoietic restoration following cyclophosphamide-induced thrombocytopenia in cynomolgus monkeys / 中国生化药物杂志

Purpose　The aim is to evaluate the effects of rhIL-11 made in China on hematopoietic recovery following chemotherapy-induced thrombocytopenia in cynomolgus monkeys.Methods　Chemotherapy-induced myelosuppression of cynomolgus monkeys was made by china iv cyclophosphamide ( 30 mg/kg, qd ) for 5 days, then animals were divided 6 groups(n=4), by sc rhIL-11( 50, 100, 200 μg/kg), or Neumega (GI rhIL-11 control, 100 μg/kg) for 14 days, another normal control and model control. Blood was taken before chemothery and then at day 3, 6,9,12,15,18,21 for blood cell counts and platelet congregate test. Bone marrow was aspirated day 0, 12 and 21 for evaluation of the megakaryocyte ploidy distribution.Results　Recovery of blood platelets was accelerated and reached normal levels by day 12, and was higher than normal day 18, day 21 sc rhIL-11 in cynomolgus moneys. Blood platelet congregated rate were 71.4%～74.6% by day 21 and higher than model control . megakaryocytes in bone marrow increased.Conclusion　rhIL-11 could accelerate the recovery of peripheral blood platelets in monkeys. The function of increased platelets was normal. The results supported the clinical use of rhIL-11 as a platelet restorative agent to prevent severe thrombocytopenia following chemotherapy.

Recent progresses in endotoxin-induced p38 MAPK signal transduction / 中国病理生理杂志

A Review The diseases caused by endotoxin have seriously affected human health. Previous studies have shown that p38 MAPK pathway is involved in the intracellular signal transduction induced by lipopolysaccharide (LPS), which plays an important role in the activation of inflammation-related cells to release inflammation mediator. Recently there have been some progresses in the isoforms distribution, substrate, molecular mechanism of regulating the release of inflammatory mediators, cellular specific activation and levels of p38 MAPK. [

Effect of epigallocatechin-3-gallate on LPS-induced p38 MAPK pathway in mouse macrophages / 中国病理生理杂志

AIM: To investigate the effect of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced p38 MAPK activation and tumor necrosis factor-? (TNF-?) secretion in macrophages. METHODS: Western blotting was used to detect the phosphorylation of p38 MAPK in mouse macrophages cultured in vitro. Enzyme linked immunosorbent assay was used to determine the secretion of TNF-? in macrophages. Electron microscopy was used to study the effect of EGCG on the structure of LPS. RESULTS: LPS caused activation of p38 MAPK and more production of TNF-?, EGCG inhibited LPS-induced phosphorylation of p38 MAPK and TNF-? production and had no effect on the structure of LPS. CONCLUSIONS: EGCG has no direct effect on LPS, but blocks cellular signal pathway. The inhibition of EGCG on LPS-induced TNF-? production is mediated, at least in part, through blocking of p38 MAPK pathway. [