Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats

Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200-250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatoctyes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats.     

Arylamine N-acetyltransferases: a new inhibitor of apoptosis in HepG2 cells

Objective  To explore how arylamine N-acetyltransferases (NATs) is related to cell apoptosis. Methods  NAT activity in apoptotic HepG2 cells was measured using high performance liquid chromatography (HPLC); the apoptosis rate of HepG2 cells acted upon by an NAT inhibitor was measured using flow cytometry. Results  NAT activity was lowered in apoptotic HepG2 cells; apoptosis rate induced by camptothecin (CAM) increased after inhibition of NAT activity in HepG2 cells. Conclusion  NAT can inhibit apoptosis in HepG2 cells. Project supported by the National Natural Science Foundation of China (No. 30400591), the Science Foundation of Heilongjiang Province, China (Nos. D2004-13 and D200505), and the Young Scientist Fund of Harbin City, China (No. 2004AFQXJ035)     

Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules

Objective  

To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.     

银杏叶总黄酮对人肝癌HepG2细胞凋亡的影响及其机制研究

目的探讨银杏叶总黄酮对体外培养的人肝癌HepG2细胞凋亡的促进作用及其分子机理。方法采用TUNEL法检测银杏叶总黄酮对HepG2细胞凋亡的影响,提取Bcl-2基因的mRNA,以RT-PCR法研究银杏叶总黄酮对Bcl-2基因表达的影响。结果银杏叶总黄酮使人HepG2细胞凋亡指数增加（P〈0．01）,且呈剂量依赖效应;Bcl-2基因mRNA水平随银杏叶总黄酮浓度升高而降低。结论银杏叶总黄酮可促进人HepG2细胞的凋亡过程,并使Bcl-2基因mRNA水平降低,从而起到抗肿瘤的治疗作用。     

骨髓间充质干细胞防治心肌细胞凋亡的Bcl-2和Bax蛋白表达研究

论文通过文献资料法、逻辑分析法等对骨髓间充质干细胞作用于心肌细胞凋亡应用,以及心肌细胞凋亡与Bcl-2和Bax蛋白表达的关系进行研究,旨在探讨骨髓间充质干细胞调控Bcl-2、Bax基因蛋白表达的方式对心肌细胞凋亡的作用机制。研究发现,心肌细胞凋亡与Bcl-2、Bax基因蛋白的表达存在高度相关性,通过调控Bcl-2、Bax的基因表达能够在一定程度上防止心肌细胞凋亡的发生与发展,而骨髓间充质干细胞则可以通过自身诱导分化的特性有效的调控Bcl-2和Bax蛋白的表达,使损伤后的心肌功能得到改善。     

Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats

Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer’s lactate solution (RS) or 5% (w/v) albumin (ALB), and the left lower lobes of the lungs were resected. Results: Albumin administered during reperfusion markedly attenuate...     

Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury

Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Methods: Experiments were conducted in male Spragne-Dawley rats (n=78) weighing 300-400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h, 24 h or continuously, followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site, rostral site and caudal site (7.5 mm away from the lesion). Results: The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day l, and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression, compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2 (Bcl-2)-associated X-protein (Bax), but not to Bcl-2, correlated with those of TUNEL-positive cells. Conclusion: Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.     

Arylamine N-acetyltransferases: a new inhibitor of apoptosis in HepG2 cells

Objective: To explore how arylamine N-acetyltransferases (NATs) is related to cell apoptosis. Methods: NAT activity in apoptotic HepG2 cells was measured using high performance liquid chromatography (HPLC); the apoptosis rate of HepG2 cells acted upon by an NAT inhibitor was measured using flow cytometry. Results: NAT activity was lowered in apoptotic HepG2 cells;apoptosis rate induced by camptothecin (CAM) increased after inhibition of NAT activity in HepG2 cells. Conclusion: NAT can inhibit apoptosis in HepG2 cells.     

A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.     

Review：BRCA1/2 associated hereditary breast cancer

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers. Project supported by the National Natural Science Foundation of China (No. 30772510) and the Joint Program of Ministry of Health and Zhejiang Provincal Government of China (No. WKJ2006-2-008)     

Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway

rectal cancer.     

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice

Objective  To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods  A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A₂ (PLA₂) in blood, and pathological changes of the hearts were investigated. Results  The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA₂ (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion  In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA₂ in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats. Projected supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province (Nos. 2003C130 and 2004C142), the Grave Foundation Project for Technological and Development of Hangzhou City (No. 2003123B19), and the Intensive Foundation Project for Technology of Hangzhou City (No. 2004Z006), China     

Prevalence of sensitization to weed pollens of Humulus scandens, Artemisia vulgaris, and Ambrosia artemisiifolia in northern China

Objective:Weed pollens are common sources of allergens worldwide.The prevalence of weed pollen sensitization is not yet fully known in China.The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia,Ambrosia,and Humulus in northern China.Methods:A total of 1144 subjects(aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources.Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris,Ambrosia artemisiifolia,and Humulus scandens,and against the purified allergens,Art v 1 and Amb a 1.Results:Of 1144 subjects,170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing.The prevalence of positive intradermal responses to pollens of Artemisia sieversiana,Artemisia annua,A.artemisiifolia,and H.scandens was 11.0%,10.2%,3.7%,and 6.6%,respectively.Among the intradermal positive subjects,the prevalence of specific IgE antigens to A.vulgaris was 58.3%,to A.artemisiifolia 14.7%,and to H.scandens 41.0%.The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%,and to Amb a 1 was 11.2%.The correlation between the presence of IgE antibodies specific to A.vulgaris and to the Art v 1 antigen was very high.Subjects with A.artemisiifolia specific IgE also had A.vulgaris specific IgE,but with relatively high levels of A.vulgaris IgE antibodies.There were no correlations between the presence of IgE antibodies to H.scandens and A.vulgaris or to H.scandens and A.artemisiifolia.Conclusions:The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%.Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.     

Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction

Background:Bone marrow mesenehymal stem cell(MSC)transplantation is a promising strategy in the treatment of myocardial infarction(MI).However,the time for transplanting cells remains controversial.The aim of this study was to find an optimal time point for cell transplantation.Methods:MSCs were isolated and cultured from Sprague-Dawley(SD) rats.MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery.MSCs were directly injected into the infarct berder zone at 1 h,1 week and 2 weeks after MI,respectively.Sham-operated and MI centrel groups received equal volume of phosphate buffered saline(PBS).At 4 weeks after MI,cardiac function Was assessed by echocardiography;vessel density Was analyzed on hematoxylin-eosin stained slides by light microscopy;the apoptosis of cardiomyocytes Was evaluated by terminal deoxynucleotidy1 transferase-mediated dUTP nick end-labeling(TUNEL) assay;the expressions of proteins were analyzed by Western blot.Results:MSC transplantation improved cardiac function.reduced the apoptosis of cardiomyocytes and increased vessel density.These benefits were more obvious in l-week group than in 1-h and 2-week groups.There are more obvious increases in the ratio of bc1-2/bax and the expression of vascular endothelial growth factor(VEGF)and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups.Conclusion:MSC transplantation was beneficial for the recovery of cardiac function.MSC transplantation at l week post-MI exerted the best effects on increases of cardiac function,anti-apoptosis and angiogenesis.     

人参皂苷Rg1对糖尿病大鼠心肌氧化应激及细胞凋亡的影响（英文）

目的:探讨人参皂苷Rg1对高血糖所致心肌损害的保护作用及其机制。创新点:使用糖尿病大鼠为实验对象,探讨三种浓度的人参皂苷Rg1对糖尿病心肌损伤的保护作用及其机制,检测其是否具有浓度依赖性。方法:将60只Wistar大鼠随机分组,其中空白对照组10只,另50只给予高脂高糖饲养,4周后腹腔注射40 mg/kg链脲佐菌素(STZ)。成功制备糖尿病大鼠模型40只,再随机分为糖尿病模型组,糖尿病大鼠+低剂量人参皂苷Rg1(10 mg/(kg·d)),糖尿病大鼠+中剂量人参皂苷Rg1(15 mg/(kg·d)),糖尿病大鼠+高剂量人参皂苷Rg1(20 mg/(kg·d))。12周后处死大鼠,取血测定空腹血糖、总胆固醇(TC)、甘油三酯(TG)、心肌酶及氧化应激水平,留取心肌组织使用透射电镜观察心肌细胞超微结构改变,应用TUNEL法检测心肌细胞凋亡,免疫组化检测细胞凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶3(CASP3)和Bcl-x L的表达。结论:人参皂苷Rg1对糖尿病大鼠糖脂代谢无明显影响,人参皂苷Rg1可降低糖尿病大鼠血清肌钙蛋白(c Tn I)和肌酸激酶同工酶(CK-MB)水平,改善心肌细胞超微结构,减少心肌细胞凋亡,降低大鼠血清和心肌组织中丙二醛(MDA)含量,提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH)水平,降低凋亡蛋白CASP3的表达,同时提高Bcl-x L蛋白表达。总之,人参皂苷Rg1能显著保护糖尿病大鼠心肌损伤,其机制可能与其抗氧化及抗细胞凋亡作用有关。     

Protective effect of recombinant Lactobacillus plantarum against H2O2-induced oxidative stress in HUVEC cells

This study probed the protective effect of recombinant Lactobacillus plantarum against hydrogen peroxide(H_2O_2)-induced oxidative stress in human umbilical vein endothelial cells(HUVECs). We constructed a new functional L. plantarum(NC8-p SIP409-alr-angiotensin-converting enzyme inhibitory peptide(ACEIP)) with a double-gene-labeled non-resistant screen as an expression vector. A 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2 H-tetrazolium bromide(MTT) colorimetric assay was carried out to determine the cell viability of HUVEC cells following pretreatment with NC8-p SIP409-alr-ACEIP. Flow cytometry(FCM) was used to determine the apoptosis rate of HUVEC cells. Cysteinyl aspartate specific proteinase(caspase)-3/8/9 activity was also assayed and western blotting was used to determine protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), inducible nitric oxide synthase(i NOS), nicotinamide adenine dinucleotide phosphate oxidase 2(gp91 phox), angiotensin II(Ang II), and angiotensin-converting enzyme 2(ACE2), as well as corresponding indicators of oxidative stress, such as reactive oxygen species(ROS), mitochondrial membrane potential(MMP), malondialdehyde(MDA),and superoxide dismutase(SOD). NC8-p SIP409-alr-ACEIP attenuated H_2O_2-induced cell death, as determined by the MTT assay. NC8-p SIP409-alr-ACEIP reduced apoptosis of HUVEC cells by FCM. In addition, compared to the positive control, the oxidative stress index of the H_2O_2-induced HUVEC(Hy-HUVEC), which was pretreated by NC8-p SIP409-alr-ACEIP, i NOS,gp91 phox, MDA, and ROS, was decreased obviously; SOD expression level was increased; caspase-3 or-9 was decreased, but caspase-8 did not change; Bcl-2/Bax ratio was increased; permeability changes of mitochondria were inhibited; and loss of transmembrane potential was prevented. Expression of the hypertension-related protein(Ang II protein) in HUVEC cells protected by NC8-p SIP409-alr-ACEIP decreased and expression of ACE2 protein increased. These plantarum results suggested that NC8-p SIP409-alr-ACEIP protects against H_2O_2-induced injury in HUVEC cells. The mechanism for this effect is related to enhancement of antioxidant capacity and apoptosis.     

Active changes of lignification-related enzymes in pepper response to Glomus intraradices and/or Phytophthora capsici

The activities of enzymes responsible for lignification in pepper, pre-inoculation with arbuscular mycorrhizal (AM) fungus ofGlomus intraradices and/or infection with pathogenic strain ofPhytophthora capsici, and the biological control effect ofG. intraradices on Phytophthora blight in pepper were investigated. The experiment was carried out with four treatments: (1) plants pre-inoculated withG. intraradices (Gi), (2) plants pre-inoculated withG. intraradices and then infected withP. capsici (Gi+Pc). (3) plants infected withP. capsici (Pc), and (4) plants without any of the two microorganisms (C). Mycorrhizal colonization rate was reduced by about 10% in pathogen challenged plants. Root mortality caused by infection ofP. capsici was completely eliminated by pre-inoculation with antagonisticG. intraradices. On the ninth day after pathogen infection, Peroxidase (POD) activity increased by 116.9% in Pc-treated roots but by only 21.2% in Gi+Pc-treated roots, compared with the control, respectively. Polyphenol oxidase (PPO) and Phenylalanine ammonia-lyase (PAL) activities gradually increased during the first 3 d and dramatically decreased in Pc-treated roots but slightly decreased in Gi+Pc-treated roots, respectively. On the ninth day after pathogen infection, PPO and PAL decreased by 62.8% and 73.9% in Pc-treated roots but by only 19.8% and 19.5% in Gi+Pc-treated roots, compared with the control, respectively. Three major POD isozymes (45000, 53000 and 114000) were present in Pc-treated roots, while two major bands (53000 and 114000) and one minor band (45000) were present in spectra of Gi+Pc-treated roots, the 45000 POD isozyme was significantly suppressed byG. intraradices, suggesting that the 45000 POD isozyme was induced by the pathogen infection but not induced by the antagonisticG. intraradices. A 60000 PPO isozyme was induced in Pc-treated roots but not induced in Gi+Pc-treated roots. All these results showed the inoculation of antagonisticG. intraradices alleviates root mortality, activates changes of lignification-related enzymes and induces some of the isozymes in pepper plants infected byP. capsici. The results suggested thatG. intraradices is a potentially effective protection agent againstP. capsici. Project supported by Korea Science and Engineering Foundation (KOSEF) through the Agricultural Plants Stress Research Center (APSRC) at Chonnam National University, Korea     

《老子》的象喻言道方式及其诗学意义

面对"道"难以言明的困境,《老子》采用了"以象言道"的方式。"象喻"是《老子》特殊的言道方式,具体表现为:取譬引喻,以水、谷等自然之"象"形容"道";执象悟道,由草木、婴儿等"象"体悟"道";以物观物,通过对"象"的整体直观抵达"道"之本质。这种言道方式是诗性的,对后世文学创作与文学批评产生了极其重要的影响,催生了意象论及"以象喻文"话语方式,开启了对澄明本真之境的审美追求。     

Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy

Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMN1 exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NAIP deletion. The findings of homozygous deletions of exon 7 and/or exon 8 of SMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion of SMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMA1. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA. Project supported by the National Natural Science Foundation of China (No. J0710043), and the Natural Science Foundation of Zhejiang Province (No. 2007C33049), China