Hypercoagulability in cats with cardiomyopathy

BACKGROUND: Arterial thromboembolism (ATE) is a common complication of feline cardiomyopathy; however, the pathogenesis of ATE is unknown. HYPOTHESIS: Systemic activation of the coagulation cascade (hypercoagulability) and endothelial injury promote ATE in cardiomyopathic cats. ANIMALS: Healthy cats (n = 30) and 3 groups of cardiomyopathic cats: Group (1) left atrial enlargement only (LAE [n = 11]), ie, left atrial to aortic ratio >1.4; Group (2) LAE with spontaneous echocardiographic contrast, atrial thrombi or both (SEC-T [n = 16]); and Group (3) acute ATE with LAE (n = 16). METHODS: Hypercoagulability was defined by 2 or more laboratory abnormalities reflecting coagulation factor excess (high fibrinogen concentration or Factor VIII coagulant activity), inhibitor deficiency (low antithrombin activity), or thrombin generation (high thrombin-antithrombin complex [TAT] and d-dimer concentrations). High von Willebrand factor antigen concentration (vWF : Ag) was considered a marker of endothelial injury. Data were analyzed using nonparametric statistics. RESULTS: The 3 groups of cats with cardiac disease had higher median fibrinogen concentrations than did the healthy cats. Criteria of hypercoagulability were found exclusively in cats with SEC-T (50%) and ATE (56%). Hypercoagulability was not associated with left atrial size or congestive heart failure (CHF). ATE cats had significantly higher median vWF : Ag concentration than did the other groups. CONCLUSION AND CLINICAL IMPORTANCE: Systemic hypercoagulability is evident in many cardiomyopathic cats, often without concurrent CHF or overt ATE. Hypercoagulabilty may represent a risk factor for ATE. High vWF : Ag in ATE cats was attributed to downstream endothelial injury from the occlusive thrombus.     

Time-course changes in the expression levels of miR-122, -155, and -21 as markers of liver cell damage,inflammation, and regeneration in acetaminophen-induced liver injury in rats

Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.     

Relationship between FRAS1 protein and brain metastases of NSCLC

AIM: To explore the relationship between FRAS1 protein and brain metastases of non-small cell lung cancer (NSCLC).METHODS: The mRNA expression of FRAS1 in the brain metastatic tumor tissues and primary tumor tissues of NSCLC was detected by qPCR. The protein expression of FRAS1 in the tumor tissues and normal tissues adjacent to tumor tissues of NSCLC was measured by SP method of immunohistochemistry. The protein expression of FRAS1 in NSCLC primary tumor tissues with or without brain metastases was also determined.RESULTS: The mRNA expression of FRAS1 in the brain metastatic zone was nearly 10 times higher than that in the primary tumor tissues, and there was significant difference between the 2 groups (P<0.05). FRAS1 protein was expressed in the NSCLC primary tumor tissues, but was not found in the normal tissues adjacent to primary tumor tissues. The protein expression of FRAS1 in the NSCLC with brain metastases was significantly higher than that without brain metastases (P<0.01).CONCLUSION: FRAS1 protein may be associated with the occurrence of NSCLC. The over-expression of FRAS1 protein may be related to brain metastases with NSCLC.     

Traditional Chinese medicine YHTJF prevents lung ischemia-reperfusion injury via caspase-12 pathway

AIM: To explore whether Yiqi Huoxue Tongluo Jiedu Fang (YHTJF) decreases the injury during lung ischemia-reperfusion (I/R) in the mice though caspase-12 pathway.METHODS: C57BL/6J male mice (n=70) were randomly divided into 7 groups: control, carboxyl methyl cellulose-Na (CMC-Na), sham, I/R, YHTJF-low (L), YHTJF-middle (M) and YHTJF-high (H) groups. YHTJF was injected intraperitoneally at 46, 92 and 184 mg/kg every day in YHTJF-L, YHTJF-M and YHTJF-H groups, respectively. The carboxyl methyl cellulose-Na was administered with the same volume of YHTJF-L in control, sham and I/R groups. After 3 h-reperfusion, the left lung tissue was harvested to determine the lung wet/dry weight ratio (W/D), the total lung water content (TLW), and index of quantitative evaluation (IQA) of alveolar damage. Morphological observation and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were applied to evaluate the structural changes and the apoptosis index (AI) of the lung tissues, respectivety. The expression of caspase-12 and glucose-regulated protein 78 (GRP78) at protein and mRNA levels in the lung tissues were detected by Western blot and RT-PCR. RESULTS: Compared with control, the W/D, TLW, IQA, AI, and the expression of caspase-12 and GRP78 at mRNA and protein levels in I/R group obviously increased (P<0.01), while no significant difference was observed between control and sham groups. Compared with I/R group, the above indexes (except GRP78) in YHTJF-L, YHTJF-M and YHTJF-H groups were all decreased (P<0.01). CONCLUSION: YHTJF may attenuate the I/R injury of the lung by inhibition of apoptosis via caspase-12 pathway.     

Variation of CD8 after traumatic brain injury in serum of rats

AIM: To explore the character of CD8 after traumatic brain injury (TBI) in peripheral blood. METHODS: Improved Feeney's free-fall method was used to set up traumatic brain injury model. The levels of neuron-specific enolase (NSE) and CD8 in the serum of the rats were detected by ELISA. The correlation of both NSE and CD8 in the serum was analyzed by Pearson product-moment correlation. The FasL expression in the lymphocytes of peripheral blood was determined by Western blot. RESULTS: The elevated level of CD8 lagged behind the level of NSE in the serum after TBI. The serum level of NSE was significantly increased at the 1st day after TBI and reached a peak at the 3rd day, subsequently gradually decreased to a lower level; the serum level of CD8 was increased at the 3rd day after TBI, and reached a peak at the 7th day, then gradually decreased. The serum levels of NSE at 1st, 3rd and 7th days were positively correlated with the serum level of CD8 at 3rd, 7th and 14th days. However, the FasL expression in the CD8⁺ lymphocytes of peripheral blood showed no variation at different time points after TBI. CONCLUSION: NSE in the serum released from neural tissues after TBI stimulates immune response and induces the augmentation of CD8 in peripheral blood, which may be a cause of secondary injuries in the brain.     

肾素血管紧张素系统(RAS)两条轴相互负向调节与大鼠非酒精性脂肪肝病(NAFLD)肝损伤的关系研究

探讨了肾素血管紧张素系统(renin angiotensin system,RAS)两条轴对大鼠非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)肝脏损伤的相互负向调节作用。30只雄性SD大鼠随机分为正常对照组、模型组和用药组。除正常对照组外,其余2组饲喂高脂饲料,用药组另外给伐他汀50 mg/kg·d。3周后,宰杀大鼠,测定血清中甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)的含量;测定肝组织匀浆羟自由基(·OH)、一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)酶活性;ELISA法测定组织匀浆中血管紧张素Ⅱ(AngⅡ)、血管紧张素1-7(Ang1-7)及白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量;Western blot分析肝组织血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)、血管紧张素Ⅱ受体1亚型(AT1R)、Mas受体(MasR)蛋白水平。结果:与正常对照组相比,模型组大鼠血清TG、AST和ALT含量以及·OH和NOS活性均显著升高(P<0.05), T-AOC、SOD活性显著降低(P<0.05);IL-1β和TNF-α含量极显著升高(P<0.01);ACE、ACE2的蛋白表达水平与ACE/ACE2的比值均显著升高(P<0.05),AngⅡ、Ang1-7含量与AT1R表达升高(P<0.05),MasR表达有升高趋势(P>0.05)。结论:高脂饲料连续饲喂3周可诱导大鼠发生NAFLD,肝脏局部RAS两条轴均处于激活状态,ACE介导AngⅡ-AT1R经典轴促进肝损伤,而ACE2介导Ang1-7-MasR轴抵抗肝损伤;ACE2负性调节RAS作用,对大鼠NAFLD时肝脏氧化应激及炎性损伤有一定保护作用。