辛伐他汀和罗格列酮对糖尿病患者动脉粥样硬化的影响

目的研究辛伐他汀和罗格列酮对2型糖尿病患者动脉粥样硬化的作用。方法 78例2型糖尿病伴颈动脉粥样斑块患者随机分为辛伐他汀组、罗格列酮组和联合组,分别口服辛伐他汀20mg/次、罗格列酮4mg/次及辛伐他汀20mg+罗格列酮4mg/次,每日1次,疗程3个月。在基线水平和疗程结束时经颈动脉超声检测CIMT,同时检测患者脂肪因子和炎症因子水平。观察治疗前后颈动脉内膜中层厚度及斑块变化。结果各组用药治疗3月后血脂、脂肪因子和炎性因子降低,CIMT厚度减低、斑块面积缩小,但斑块数量无减少,且联合用药比单一用药效果更显著。结论 2型糖尿病患者联合使用辛伐他汀和罗格列酮可改善胰岛素抵抗、改善脂类代谢、抑制大血管炎症反应、稳定和缩小动脉粥样斑块。     

Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress,inflammation and caspase-3

Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer.Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activitypresent in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate thenephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistaralbino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats receivedboldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip)was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidneyindex. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS,an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities andtumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Induciblenitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicityinduced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, anddecreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at bothboldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathologicalfindings supported biochemical findings. Taken together these findings indicate that boldine has promising protectiveeffect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations andby alleviating caspase 3 expression.     

Association between preterm birth risk and polymorphism and expression of the DNA repair genes <i>OGG1</i> and <i>APE1</i> in Saudi women

Genomic instability and mutations caused by increases in oxidative stress during pregnancy can damage the fetoplacental unit and can upshot preterm birth. Oxidative damage to DNA may possibly be involved in etiology of preterm birth (PTB) which can be repaired by DNA repair gene. In the present study, we assessed the association of base excision repair gene family by analyzing the association of single nucleotide polymorphisms and genes expression in 8-oxoguanine glycosylase-1 (OGG1) and apurinic-apyrimidinic endonuclease 1 (APE1) genes with risk of preterm birth in Saudi women. We analyzed genotypes of four single nucleotide polymorphisms (SNPs) (rs1052133, rs293795, rs2072668 and rs2075747) in OGG1 gene and three SNPs (rs1130409, rs3136814, and rs3136817) in APE1 gene using TaqMan Genotyping assay kits in 50 pairs of preterm cases and individually matched controls. Also, gene expression level was explored by RT-PCR in 10 pairs of preterm placental tissues and individually matched normal placental tissues. Two OGG1 SNP, rs1052133 (OR=0.497; c2=1.11; p=0.292) and rs2072668 (OR=0.408; c2=1.90; p=0.167) and one APE1 SNP rs3136817 (OR=0.458; c2=0.40; p=0.527) showed nonsignificant protective effect against PTB development. The expression of both genes under study was found lower in the PTB patients. Genotype and allele frequencies of both gene SNPs did not show any association with the risk of preterm delivery in Saudi women (P˃0.05). However, synthesis and release of OGG1 and APE1 proteins decreased in preterm placental tissues compared to term delivery reflects the probability of being one of the mechanisms leading to preterm birth.     

Cardioprotective effect of ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway in myocardial ischemia/reperfusion injury induced in H9c2 cell

Post-resuscitation myocardial dysfunction (PRMD) is the most severe myocardial ischemia-reperfusion injury(MIRI) and is characterized by difficult treatment and poor prognosis. Research has shown the protective effects of therational use of ivabradine (IVA) against PRMD; however, the molecular mechanisms of IVA remain unknown. In thisstudy, an ischemia-reperfusion injury (IRI) model was established using hypoxic chambers. The results demonstratedthat pretreatment with IVA reduced IRI-induced cytotoxicity and apoptosis. IVA attenuated mitochondrial damage,eliminated excess reactive oxygen species (ROS), suppressed IRI-induced ATP and NAD⁺, and increased theAMP/ATP ratio. We further found that IVA increased the mRNA levels of sirtuin 1 (SIRT1) and peroxisomeproliferator-activated receptor-γ coactivator 1α (PGC-1α) and upregulated the expression levels of phosphorylatedAMP-activated protein kinase (p-AMPK)/AMPK, SIRT1, and PGC-1α proteins. Interestingly, no change in AMPKmRNA levels was observed. Cardiomyocyte energy metabolism significantly changed after IRI. The aim of this studywas to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1α signaling pathway inmyocardial ischemia/reperfusion injury-induced in H9c2 cell.     

20(R)-ginsenoside Rg3, a product of high-efficiency thermal deglycosylation of ginsenoside Rd,exerts protective effects against scrotal heat-induced spermatogenic damage in mice

Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular andvarious organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and canprotect against multiple organs, also used as functional food to adjust the balance of the human body, but thetherapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim ofthe present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate thecontribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows:normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, thenexposed to a single scrotal heat treatment (43°C, 18min) on the 7th day. After HS treatment, the morphology of testisand epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells indestructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. Afteradministration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels andsuperoxide dismutase (SOD) activity, glutathione (GSH) content significantly (p < 0.01) increase compared with theHS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) (p < 0.05 orp < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing theprotein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), and heat shock protein 70 (HSP70)but also modulating the Bcl-2 family (p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase(MAPK) signaling pathways (p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibitedpotent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present studydemonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting theMAPK-mediated oxidative stress and apoptosis in mice.     

Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway

Scutellarin (SCU) is a herbal flavonoid glucuronide with multiple pharmacological activities, including anti-oxidant, anti-inflammation, vascular relaxation, anti-platelet, and myocardial protection. However, the effect of SCU on complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) had not been studied. In this study, we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma levels of immunoglobulin (Ig)G, IgE, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG). Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints. The proportions of T helper type 1 (Th1) and T helper type 2 (Th2) cells of CD4+ T lymphocyte subsets were analyzed by flow cytometry. The expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was analyzed using real-time quantitative PCR (RT-qPCR) and western blotting assays. The present study demonstrated that SCU prevented CFA-induced RA, and inhibited the expression of inflammation factors, IgG, IgE, TNF-α, IL-1β, and IL-6. While SCU also reduced the RANKL level, it increased OPG expression in RA mice. The Th1/Th2 ratio was significantly lower in mice treated with SCU. Additionally, HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment. Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.     

Astaxanthin delayed the pathogenesis of diabetic nephropathy in type 1 diabetic rats

This study was designed to investigate the protective effects of Astaxanthin (AST) in rats with diabetes mellitus(DM) induced by streptozotocin. SD rats were divided into control group (n = 5, only received normal saline), DM group(n = 8) and AST + DM group (n = 8; AST: 50 mg/kg/day). DM rats were induced by intraperitoneal injection ofstreptozocin (STZ, 65 mg/kg). Blood glucose level and body weight were determined at weeks 0, 2, 4, 6 and 8,respectively. At week 8, kidney function was determined, together with expression of P53 and dynamin-relatedprotein-1 (Drp1) by Western blot analysis and immunofluorescence. AST led to increase of body weight in rats withDM. AST + DM group showed a significant decrease in blood glucose level at week 4 compared with DM group(P < 0.05). AST improved renal function and significantly reduced expression of P53 and Drp1 in DM rats. Inaddition, AST can effectively reduce the blood glucose in DM rats, and delayed the pathogenesis of diabeticnephropathy. Such delay mediated by AST may be associated with the downregulation of Drp1 and P53.     

Caveolin-1 and mitochondrial alterations in regenerating rat liver

The liver has a remarkable ability to regenerate after partial hepatectomy (PH), although the factors governing such ability are still poorly understood. During the prereplicative phase of the regeneration, ultrastructural alterations of periportal hepatocytes were seen, including mitochondrial swelling, abnormal accumulation of lipids, and myelin figures which could lead to the formation of lipid droplets. As it has been hypothesized that caveolin-1 is involved in lipidogenesis and in mitochondrial homeostasis, we aimed to study the subcellular distribution of caveolin-1 in hepatocytes at an early stage following PH. Liver samples were processed for light and electron microscopy at 0 h, 24 h, and 96 h after PH. The expression and subcellular distribution of caveolin-1 was assessed by immunohistochemical and immunocytochemical techniques. Following PH, at 24 h, membranes of altered mitochondria of periportal hepatocytes exhibited significant decrease of caveolin-1 expression compared with control. Myelin figures showing high expression of caveolin-1 were also seen. At 96 h, hepatocytes became ultrastructurally similar to the control liver, and the expression of caveolin-1 on mitochondria showed a moderate increase compared with 24 h after PH. Decrease of expression of caveolin-1 in the altered liver mitochondrial membranes at 24 h following PH, and the high expression of caveolin-1 observed on myelin figures, suggests involvement of caveolin-1 is in both mitochondrial homeostasis and lipidogenesis. Addressing the role played by caveolin-1 during liver regeneration might disclose additional features of mitochondrial homeostasis and lipidogenesis during frequent metabolic liver diseases.     

低合金高强钢焊接构件在高温锅炉水中的应力腐蚀开裂行为研究

分析了某公司的2#乙二醇R-120环氧乙烷反应器中C-11环焊缝开裂原因。对开裂C-11环焊缝开展了化学成分、金相观察、硬度测试、断口微观观察、EDS能谱分析等试验研究。试验发现：壳程、管板母材和焊缝金属化学成分分别满足SA543 Type B CL.1,SA508 Gr.4N CL.1和MGS 80的要求;从内壁管板侧热影响区起裂的主裂纹穿晶扩展,裂纹尖端沿晶扩展并有分叉,具有应力腐蚀裂纹特征;内壁附近焊缝两侧热影响区局部有马氏体组织;管板侧热影响区硬度最高为466.3 HV10;断口观察发现裂纹在内壁产生,是多源裂纹,沿壁厚向外壁扩展15 mm,断口上有冰糖状等轴晶和柱状晶;裂纹断口探测到P和Na元素。该反应器开裂原因是由于焊接导致在管板与壳程焊接区域存在较高的残余应力,在高温锅炉水介质中,发生了应力腐蚀开裂,由内壁向外扩展,最终导致泄漏。     

Bushen Yizhi Formula regulates the IRE1α pathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

Background: While the Bushen Yizhi Formula can treat Alzheimer’s disease (AD), the yet to be ascertainedspecific mechanism of action was explored in this work. Methods: Different concentrations of the Bushen YizhiFormula and amyloid-beta peptide (Aβ) were used to treat rat pheochromocytoma cells (P12) and humanneuroblastoma cells (SH-SY5Y). Cell morphological changes were observed to determine the in vitro cell damage. CellCounting Kit (CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively. Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmicreticulum stress (ERS)-related proteins (GRP78 and CHOP), p-IRE1α, IRE1α, ASK1, p-JNK, JNK, Bax, Bcl-2, XBP-1,and Bim. Fura 2-acetoxymethyl ester (Fura-2/AM) was used to determine the intracellular calcium (Ca²⁺)concentration. Also, an AD model was constructed by injecting Aβ into the CA1 area of the hippocampus in SpragueDawley rats. AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutivedays. The Morris water maze experiment was conducted to test the learning and memory of rats. Hematoxylin &Eosin (H&E) and Terminal-deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL)staining were done to determine histopathological changes in the brain. Results: Bushen Yizhi Formula relieved theAβ-induced effects including cell injury, decreased viability, increased apoptosis, G0/G1 phase cell cycle arrest, upregulation of GRP78, CHOP, p-IRE1α, p-JNK, Bax, XBP-1 and Bim, as well as down-regulation of Bcl-2. Theseresults were also seen with IRE1α silencing. While Aβ suppressed the learning and memory abilities of rats, theBushen Yizhi Formula alleviated these effects of Aβ. Brain nerve cell injury induced by Aβ could also be treated withBushen Yizhi Formula. Conclusion: Bushen Yizhi Formula could influence ERS through the IRE1α signaling pathwayto achieve its therapeutic effects on AD.     

5-HT 1A and 2A receptor positive cells in the cerebella of mice and human and their decline during aging

This study evaluated the 5-HT1A and 5-HT2A receptor positive cells in the cerebella of mice and human by immunocytochemistry. Mice were of ages 1, 3, and 12 months whereas the human subjects were divided into two groups, a younger 57–78 years old group and an older 82–91 years old group. Both 5-HT1A and 5-HT2A receptor positive cells were observed in the molecular and granular layers of the cerebella of mice and human. Although there was a decline in these positive cells during aging, no regional difference in the positive cells were observed in the anterior, middle, and posterior regions of the cerebella. Microsc. Res. Tech. 2009. © 2009 Wiley-Liss, Inc.     

Ultrastructural localization of defined sequences of viral RNA and DNA by in situ hybridization of biotinylated DNA probes on sections of herpes simplex virus type 1 infected cells

The influence of fixation and enzymatic digestions on the ability of a denatured double-stranded DNA probe to bind specifically to related sequences of RNA and DNA in sections of Lowicryl embedded cells was investigated. Specificity of the hybridization was assessed using a biotinylated cloned subgenomic herpes simplex virus type 1 DNA fragment to localize viral nucleic acids in sections of infected cells. The probe was detected by anti-biotin antibodies and indirect immunogold labeling. Controls indicated that protease digestion of proteins from the section eliminated non-specific binding of the probe and labeling of endogenous biotin. Both formaldehyde and glutaraldehyde fixation retained viral RNA in protease digested sections. Its labeling was randomly and sparsely distributed over the fibrillo-granular network of the infected nucleus and over the ribosome-rich regions of cytoplasm. Labeling of single-stranded portions of viral DNA in protease-RNase digested sections was infrequent. It was located precisely over nucleoids of a few viral nucleocapsids whatever their location in the cell and their stage of maturation. Labeling of double-stranded viral DNA by denaturation of the DNA in the sections of Lowicryl embedded cells was possible after fixation with formaldehyde but not glutaraldehyde. Among several denaturation protocols, 0.5 N NaOH treatment was best for hybridization of both nonencapsidated and encapsidated viral DNA in protease-RNase digested sections. Free viral genomes were detected exclusively within the virus-replicating region of infected nuclei. Labeling of viral nucleoids was independent of their location in the cell. The high percentage of labeled viral nucleoids suggests that the related viral DNA sequence is not aggregated in the nucleoid but is extended and therefore numerous portions of this defined DNA sequence are accessible at the surface of the section for the binding of the probe.