Protective effect of butylated hydroxylanisole against hydrogen peroxide-induced apoptosis in primary cultured mouse hepatocytes

Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H₂O₂)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H₂O₂ in a dose-dependent manner. Additionally, H₂O₂ treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H₂O₂ significantly attenuated the H₂O₂-induced decrease of cell viability. H₂O₂ exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H₂O₂-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H₂O₂-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H₂O₂-induced apoptosis by inhibiting ROS generation.     

苦参碱对奶牛乳腺上皮细胞增殖、凋亡及抗氧化能力的影响

【目的】探究苦参碱对体外培养的奶牛乳腺上皮细胞(BMECs)增殖、凋亡及抗氧化能力的影响。【方法】利用含0(A组),25(B组),50(C组),75(D组)和100μg/mL(E组)苦参碱的培养基培养奶牛乳腺上皮细胞。通过四甲基偶氮唑盐(MTT)法检测BMECs活性,采用流式细胞仪(AnnexinV/PI双染法)检测苦参碱对BMECs凋亡的影响,并检测苦参碱对BMECs抗氧化酶活性及丙二醛(MDA)含量的影响,采用real-time PCR对BMECs中Caspase-3、p53、STAT1和SOCS3基因的相对表达量进行检测。【结果】用药5d时,低质量浓度(25和50μg/mL)苦参碱对BMECs增殖具有促进作用,高质量浓度(75和100μg/mL)苦参碱对细胞增殖具有抑制作用;B~E组BMECs的凋亡率均极显著高于A组(P0.01);B~E组BMECs培养上清液中NO和乳酸脱氢酶(LDH)水平明显高于A组。B~E组BMECs的过氧化氢酶(CAT)活性均比A组高,其中C组极显著高于A组(P0.01);B~E组的谷胱甘肽过氧化物酶(GSH-Px)活性均极显著高于A组(P0.01),E组的超氧化物歧化酶(SOD)水平极显著高于A组(P0.01),各组MDA含量无显著性差异。与A组相比,苦参碱上调了B~E组BMECs中Caspase-3、p53、STAT1和SOCS3基因的相对表达量。【结论】低质量浓度苦参碱能够促进BMECs增殖,高质量浓度苦参碱则会抑制BMECs增殖;不同质量浓度苦参碱均可提高BMECs的抗氧化能力,其中50μg/mL苦参碱提高BMECs抗氧化能力的效果最明显。     

Phenolic extract of Morchella angusticeps peck inhibited the proliferation of HepG2 cells in vitro by inducing the signal transduction pathway of p38/MAPK

Morchella angusticeps Peck, one of the most popular edible mushrooms, has attracted great attention due to its delicious taste and healthy properties. However, both its biological effects and the possible mechanism of action have not yet been known. We investigated the anti-proliferative activity of the phenolic extract derived from Morchella angusticeps Peck (MPE) against HepG2 human hepatocellular carcinoma cells. Results showed that MPE at non-cytotoxicity doses significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner with inhibitory rates ranging from 18 to 90% (P<0.01). The possible mechanism might be that MPE induced apoptosis through initiating the mitochondrial death pathway by regulating Bax, Bcl-2 and cleaved caspase-3. On the other hand, MPE might trigger cell cycle arrest at G₀/G₁/S phases by managing p21, Cyclin D1, cyclin-dependent kinases-4 (CDK4) and proliferating cell nuclear antigen (PCNA). Additionally, MPE downregulated TRAF-2 and p-p53, while upregulated p-ASK1 and p-p38. Therefore, it could be inferred that MPE might induce the anti-proliferative function to HepG2 cells through the p38/MAPK signal transduction pathway.     

Deficits of learning and memory in Hemojuvelin knockout mice

Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(−/−) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(−/−) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(−/−) mice would be a useful model to study cognitive impairment induced by iron overload in brain.     

Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential

There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.     

基于热致液晶弹性体的仿生心脏泵的设计

为设计一款仿生心脏功能较佳的心室泵,采用柔性、热致伸缩的热致形变弹性体代替心肌,根据螺旋心室心肌带理论,选择心肌带的左心室段,并选取了Hilbert平面填充曲线作为热致导体在热致形变弹性体中的走行方式,设计出与真实心脏类似的心室泵结构.通过试验测量了所设计的心室泵的射血分数与心率,结果显示该心室泵的搏出量高于自然心脏,而其心率远低于自然心脏.相对于机械泵,所设计的心室泵结构与真实心脏类似,具有收缩能力强,射血分数高的优点,且不易破坏血细胞,生物相容性较好.不足之处在于,热致动液晶弹性体变形响应慢,暂时还未能达到正常心脏的心率.论证了构建双稳态结构,提高仿生心室泵效率的可能性,以及对于心肌纤维走向较为复杂的其他心肌带段,双轴拉伸机械雕刻对其仿生的可能性.此研究可为容积心脏泵的研发提供新的思路,也可以对右心衰竭等心脏疾病起到辅助治疗的作用.     

Effects of dissolved oxygen on the growth performance,haematological parameters,antioxidant responses and apoptosis of juvenile GIFT (Oreochromis niloticus)

This study investigated the effects of different dissolved oxygen (DO) levels on the growth performance, antioxidant response and apoptosis of juvenile GIFT (genetically improved farmed tilapia, Oreochromis niloticus). GIFT were fed with five DO levels (1, 2, 3, 4 and 5 mg/L) for 60 days, and the results showed that the final body weight, weight gain rate, specific growth rate and crude protein and crude lipid contents of the fish muscle increased at 5 mg/L DO. The activities of the antioxidant and digestive enzymes were significantly up‐regulated with increasing DO levels. However, the haemoglobin content, number of red blood cells, malondialdehyde content, transaminase activities, glucose content and lactic acid levels decreased at higher DO levels. Furthermore, the cardiomyocyte apoptotic index was significantly decreased with increasing DO levels. Our results show that 5 mg/L DO improved growth performance, promoted antioxidant enzyme activities and reduced liver damage in GIFT.     

Identification of a mitochondrial‐targeting secretory protein from Nocardia seriolae which induces apoptosis in fathead minnow cells

Nocardia seriolae is the main pathogen responsible for fish nocardiosis. A mitochondrial‐targeting secretory protein (MTSP) 3141 with an N‐terminal transit peptide (TP) from N. seriolae was predicted by bioinformatic analysis based on the genomic sequence of the N. seriolae strain ZJ0503. However, the function of the MTSP3141 and its homologs remains totally unknown. In this study, mass spectrometry analysis of the extracellular products from N. seriolae proved that MTSP3141 was a secretory protein, subcellular localization research showed the MTSP3141‐GFP fusion protein co‐localized with mitochondria in fathead minnow (FHM) cells, the TP played an important role in mitochondria targeting, and only the TP located at N‐terminus but not C‐terminus can lead to mitochondria directing. Moreover, quantitative assays of mitochondrial membrane potential (ΔΨm) value, caspase‐3 activity and apoptosis‐related gene (Bcl‐2, Bax, Bad, Bid and p53) mRNA expression suggested that cell apoptosis was induced in FHM cells by the overexpression of both MTSP3141 and MTSP3141ΔTP (with the N‐terminal TP deleted) proteins. Taken together, the results of this study indicated that the MTSP3141 of N. seriolae was a secretory protein, might target mitochondria, induce apoptosis in host cells and function as a virulence factor.     

Effect of hydrogen sulfide on myocardial fibrosis and PPARγ and NF-κB expression in rat model of diabetes

AIM: To explore the effects of hydrogen sulfide (H₂S) on the myocardial fibrosis in a rat model of diabetes and its mechanism.METHODS: Single intraperitoneal injection of streptozotocin (STZ) was utilized to establish a rat model of diabetes. Sodium hydrosulfide was used as an exogenous donor of hydrogen sulfide. Male SD rats were randomly divided into control group, STZ group, STZ+H₂S group and H₂S group. Eight weeks later, HE and VG staining methods were used to observe the collagen distribution and collagen volume fraction was measured by image analysis. The expression levels of type I collagen, PPARγ and NF-κB in the cardiac tissues were determined by Western blotting.RESULTS: Compared with control group, collagen distribution and the expression levels of type I collagen and NF-κB in the cardiac tissues were markedly increased (P<0.05), while PPARγ was significantly decreased in STZ group (P<0.05), but these indexes were reversed significantly in STZ+H₂S group (P<0.05). The expression levels of type I collagen, PPARγ and NF-κB had no significant difference between H₂S group and control group.CONCLUSION: Hydrogen sulfide attenuates cardiac fibrosis in diabetic rats, and its mechanism may be related to PPARγ-NF-κB signaling pathway.