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1.
The sarcoplasmic reticulum was isolated and characterized in the pure form from normal caprine (Capra hircus) hearts. Under ischemic condition, fatty acids like palmitic acid, palmitoyl carnitine and oleic acid accumulatein vivo. These are known to have a detrimental effect on membrane components. The effects of simulated ischemia on the Ca2+-ATPase were studied using these fatty acidsin vitro at concentrations at which they occurin vivo in the ischemic heart. All three fatty acids inhibited Ca2+-ATPase activity. At lower concentrations, palmitoyl carnitine was the most potent, followed by oleic acid while palmitic acid displayed the least potency. Electron microscopy studies with fatty acids showed morphological disruptions in SR vesicles. The decline in Ca2+-ATPase activity could be attributed to the change in membrane morphology.  相似文献   

2.
Twenty four Wistar strain albino rats were used for the investigations. Lecithin 50 and 100 mg/kg b wt was administered for 1 week by oral route. Liver damage was induced by intra peritoneal administration of 400 mg/kg b wt d-galactosamine on the last day. At the end of the study animals were sacrificed and liver enzyme levels, histopathology, mitochondrial integrity, expression of p53, Bax and Bcl-2 mRNA levels were studied. Increases in the liver enzyme levels by d-GalN were significantly inhibited by pretreatment with lecithin. Histopathological observation further confirmed the hepatoprotective effect of lecithin. In addition, the disruption of mitochondrial membrane, up regulation of Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with lecithin. The results of the present study validate our conviction that d-GalN causes hepatic damage via mitochondrial pathway involving Bax and Bcl-2.  相似文献   

3.
Objective of this study was to obtain a better understanding of the mechanism responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100 mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced by intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day of catechin treatment. At the end of treatment all animals were killed and liver enzyme levels were estimated. Dissected hepatic samples were used for histopathology, RNA isolation, expression studies of Bax, Bcl-2 and p53 mRNA levels and mitochondrial membrane potential studies. We found that increases in the liver enzyme activity and decrease in antioxidant enzyme activity by d-GalN were significantly restricted by oral pretreatment with catechin. Disruption of mitochondrial membrane potential, up regulation of p53, Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with catechin.  相似文献   

4.
The development of reactive oxygen species (ROS) generation agents that can selectively produce sufficient ROS at the tumor site without external energy stimulation is of great significance for the further clinical application of ROS-based therapies. Herein, we designed a cascade-responsive ROS nanobomb (ZnO2@Ce6/CaP@CPPO/BSA, designated as Z@Ce6/CaP@CB) with domino effect and without external stimulation for the specific generation of multiple powerful ROS storms at the tumor site. The calcium phosphate shell and ZnO2 core gradually degrade and release Ca2+, Zn2+ and hydrogen peroxide (H2O2) under acid stimulation. On the one hand, Zn2+ can enhance the generation of endogenous superoxide anions (·O2–) and H2O2 through the inhibition of the mitochondrial electron transport chain. On the other hand, the generation of large amounts of exogenous H2O2 can cause oxidative damage to tumor cells and further activate bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-mediated chemiexcited photodynamic therapy. In addition, the oxidative stress caused by the generated ROS can lead to the uncontrolled accumulation of Ca2+ in cells and further result in Ca2+ overload-induced cell death. Therefore, the introduction of Z@Ce6/CaP@CB nanobombs triggered the ‘domino effect’ that caused multiple heavy ROS storms and Ca2+ overload in tumors and effectively activated anti-tumor immune response.  相似文献   

5.
Iron is an essential nutrient for a number of cellular activities. However, excess cellular iron can be toxic by producing reactive oxygen species (ROS) such as superoxide anion (O2−) and hydroxyl radical (HO·) that damage proteins, lipids and DNA. Mutagenic and genotoxic end products of lipid peroxidation can induce the decline of mitochondrial respiration and are associated with various human ailments including aging, neurodegenerative disorders, cancer etc. Zingiber officinale Roscoe (ginger) is a widely used spice around the world. The protective effect of aqueous ethanol extract of Z. officinale against ROS-induced in vitro lipid peroxidation and DNA damage was evaluated in this study. The lipid peroxidation was induced by hydroxyl radical generated from Fenton’s reaction in rat liver and brain homogenates and mitochondrial fraction (isolated from rat liver). The DNA protection was evaluated using H2O2-induced changes in pBR-322 plasmid and Fenton reaction-induced DNA fragmentation in rat liver. The results indicated that Z. officinale significantly (P<0.001) protected the lipid peroxidation in all the tissue homogenate/mitochondria. The extract at 2 and 0.5 mg/ml could protect 92 % of the lipid peroxidation in brain homogenate and liver mitochondria respectively. The percent inhibition of lipid peroxidation at 1mg/ml of Z. officinale in the liver homogenate was 94 %. However, the extract could partially alleviate the DNA damage. The protective mechanism can be correlated to the radical scavenging property of Z. officinale. The results of the study suggest the possible nutraceutical role of Z. officinale against the oxidative stress induced human ailments.  相似文献   

6.
The EGF-R, also known as HER-1 or erbB-1 (EGF-R/HER-1/erbB-1), is a member of the human epithelial receptor tyrosine kinase family. sEGF-R is considered to play a role in cardiac (patho)physiology. We aimed to investigate whether soluble EGF-R is increased in congestive heart failure (CHF) patients and if related to disease severity. Soluble EGF-R, vitamin D, parathyroid hormone (PTH) was studied, and being evaluated in relation to Ca2+, lipids, hsCRP, fibrinogen, serotonin, norepinepherine (NE). The study compared non-smoker, non-obese male CHF patients (n = 50) with age and gender-matched essential hypertension (HTN) patients (n = 20). Moreover, comparison with healthy control volunteers (n = 20) were employed. EGF-R/HER-1/erbB-1 was higher (P = 0.013) in 50 CHF male patients mean 12 ± 0.7 fmol/ml, than in 20 HTN, 9.25 ± 0.6 fmol/ml or in 20 controls, 6.25 ± 1 fmol/ml. Serum EGF-R levels correlated positively with hsCRP and NE, and were highest among CVD patients (n = 70) as well as negatively with vitamin D and HDL-C. EGF-R/HER-1/erbB-1 levels are increased in HTN and more in CHF patients. This study confirms a strong association between catecholamines as well as EGF-R/HER-1/erbB-1 levels with PTH and low vitamin D levels, being related to hyperlipidemia and inflammation (hsCRP and fibrinogen) in CVD. Moreover, contributing to the complex process of the inflammatory component of atherosclerosis in hypertensive patients that leads eventually to CHF.  相似文献   

7.
BackgroundThe heterologous expression of parasitic proteins is challenging because the sequence composition often differs significantly from host preferences. However, the production of such proteins is important because they are potential drug targets and can be screened for interactions with new lead compounds. Here we compared two expression systems for the production of an active recombinant aldehyde dehydrogenase (SmALDH_312) from Schistosoma mansoni, which causes the neglected tropical disease schistosomiasis.ResultsWe produced SmALDH_312 successfully in the bacterium Escherichia coli and in the baculovirus expression vector system (BEVS). Both versions of the recombinant protein were found to be active in vitro, but the BEVS-derived enzyme showed 3.7-fold higher specific activity and was selected for further characterization. We investigated the influence of Mg2+, Ca2+ and Mn2+, and found out that the specific activity of the enzyme increased 1.5-fold in the presence of 0.5 mM Mg2+. Finally, we characterized the kinetic properties of the enzyme using a design-of-experiment approach, revealing optimal activity at pH 7.6 and 41°C.ConclusionsAlthough, E. coli has many advantages, such as rapid expression, high yields and low costs, this system was outperformed by BEVS for the production of a schistosome ALDH. BEVS therefore provides an opportunity for the expression and subsequent evaluation of schistosome enzymes as drug targets.How to cite: Harnischfeger J, Beutler M, Salzig D, et al. Biochemical characterization of the recombinant schistosome tegumental protein SmALDH_312 produced in E. coli and baculovirus expression vector system. Electron J Biotechnol 2021;54. https://doi.org/10.1016/j.ejbt.2021.08.002  相似文献   

8.
Special Lectures     
Calcineurin, a Ca2+—Calmodulin dependent protein phosphatase, is important for Ca2+ mediated signal transduction. The main objective of this study was to examine the potential role of calcineurin in idiopathic mental handicap. Calcineurin levels were estimated in 20 children in the age group of 5–16 years with idiopathic mental handicap attending the Special. Education Centre for the Mentally Handicapped in Hyderabad. The results of the present study showed decreased activity of serum calcineurin in children with idiopathic mental handicap compared to those of normal subjects in the same age group. The observations thus suggest impaired calcineurin activity in children with mental handicap. Calcineurin that is involved in biosynthesis and release of neurotransmitters at the synaptic terminal brain is affected thereby causing brain damage and leading to mental handicap. Impaired calcineurin activity was already indicated in many human diseases such as Down's syndrome, Alzheimers, Brain ischemia, cardiac hypertrophy etc. It is therefore necessary to check the calcineurin levels in children with mental handicap to understand the role of calcineurin in the causation of Mental handicap.  相似文献   

9.
To examine the possible involvement of human B cell leukemia/lymphoma 2 (Bcl-2), CD4+ cells, hepatocyte growth factor (HGF), and metalloproteinase-9 (MMP-9), as biomarkers in early diagnosis of hepatocellular carcinoma (HCC), activities of these biomarkers in serum were demonstrated by the method of Enzyme Linked Immunosorbant Assay. Two groups of subjects (60 for each), were examined in this study; healthy controls and patients with HCC. The present results declare that, significant decrease in Bcl-2 (p ≤ 0.0001), and CD 4+ (p ≤ 0.001), while significant increase in HGF and MMP-9 (p ≤ 0.05). These findings imply an influence of these biomarkers by the existence of hepatic carcinoma that might reflect the progression of disease and a distinction between the pathological mechanisms involved in hepatic carcinoma. Since, the serum MMP-9 activity was significantly varied between each stage of HCC. An individual profile of the present investigated parameters was detected that might serve as an easy accessing serum marker to monitor the progression of hepatic cell disorders.  相似文献   

10.
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11.
Aqueous extract of the wood ofPterocarpus marsupium, commonly known as ‘bijasar’, is used in Indian Ayurveda system of medicine for treatment of diabetes. The active anti-diabetic principle in its aqueous extract has been found to be (-)epicatechin, a flavonoid. The present work was undertaken to study the effect of (-)epicatechin on erythrocyte membrane Ca++-ATPase from type 2 diabetic patients. The activity of erythrocyte Ca++-ATPase was significantly lower in type 2 diabetics.In vitro insulin treatment of erythrocyte ghosts, resulted in the increase of Ca++-ATPase activity in diabetic patients. Treatment with (-)epicatechin (1mM) resulted in an increase in the activity of erythrocyte Ca++-ATPase in both normal individuals and type 2 diabetic patients. The insulin like effect of (-)epicatechin on erythrocyte membrane Ca++-ATPase in type 2 diabetics is an interesting finding. Further work is needed to elucidate the mechanism of action of (-)epicatechin on modulation of erythrocyte membrane bound enzymes.  相似文献   

12.
天山乌鲁木齐河源区径流水化学特征及影响因素分析   总被引：3，自引：0，他引：3  
冯芳  李忠勤  张明军  金爽  王飞腾 《资源科学》2011,33(12):2238-2247
在乌鲁木齐河源区采集两年的大气降水和1号冰川、空冰斗、总控3个水文点逐日定时径流样品,对主要离子、pH、电导率EC和总溶解固体TDS进行了分析。结果表明,大气降水离子类型为Ca^2＋-Na^＋-HCO3--SO4^2-,接近中性;径流离子类型为Ca^2＋-Na^＋-HCO3--SO4^2-,呈弱碱性。径流中EC和TDS均值总控〉1号冰川〉空冰斗,其中1号冰川径流的峰值远高于其它两个水文点。受不同下垫面的影响,1号冰川水文点TDS变化受日径流量影响显著,而空冰斗水文点基本不受影响。径流中离子组成主要受岩石风化作用影响,离子比值和Piper图分析说明控制径流离子的主要过程是碳酸盐、黄铁矿和长石类矿物风化。海盐校正分析得出,大气降水对1号冰川、空冰斗、总控径流离子贡献率分别为4.91％,9．10％和5．42％。通过阳离子通量计算,2006年、2007年1号冰川径流的化学风化侵蚀率分别为18．1t／（km^2·a）和12．3t／（km^2·a）。  相似文献   

13.
The effect of DL α-lipoic acid, a potent antioxidant was studied in relation to certain erythrocyte membrane parameters in calcium oxalate stone forming rats. Induction of calcium oxalate lithiasis was done by feeding a diet containing 3% w/w sodium glycollate. Erythrocyte membrane (Na+, K+)-ATPase showed a significant decrease in stone formers whereas (Ca2+)-ATPase showed a significant increase. Lipoic acid administration brought about an elevation in the activity of (Ca2+)-ATPase. Changes in membrane (Mg2+)-ATPase was minimal. Membrane cholesterol and phospholipids were found raised significantly in lithogenic rats. The changes may be attributed to enhanced lipid peroxidative mechanisms and altered serum lipid profile observed in this group. Treatment with lipoic acid reduced membrane cholesterol levels. Phospholipids were also decreased moderately. The above observations suggest that lipoic acid administration to calculogenic rats reduces the erythrocyte strucutral changes observed in this condition.  相似文献   

14.
This review presents the extensive work carried out on lipid components of dermatophytes, their biosynthesis, turnover and regulation. It emerges from the work done so far that the pathways of lipid biosynthesis/ degradation and the lipid composition in dermatophytes are similar to those in yeasts and other fungi. Second messengers (Ca2+, cAMP) were demonstrated to have a regulatory role in phospholipid metabolism and they mainly act by stimulating Ca2+/CaM or cAMP dependent protein kinase(s). Both these kinases were purified and characterized inMicrosporum gypseum. Further work is being carried out to elucidate the molecular mechanism of regulation of phospholipid metabolism by these second messengers.  相似文献   

15.
Cardiac mitochondria provide energy for the contraction/relaxation cycle. The aim of our study was to isolate and characterize mitochondria from Caprine hearts under control and in-vitro induced ischemia. A decrease in activities of all the enzymes was observed in the ischemic models. Further characterization of proteins was done by SDS-PAGE and BN-PAGE. Lipids have been characterized by analyzing the phospholipids by HPTLC and fatty acids by GLC in both groups. Our results indicated that injury occurs early in the course of ischemia and progresses during ischemia. TBARS and carbonyl content have also been measured. The in-vitro effects of fatty acids have been studied on the enzymes and complexes of mitochondria.  相似文献   

16.
BackgroundMyostatin (MSTN) negatively regulates muscle mass and is a potent regulator of energy metabolism. However, MSTN knockout have affect mitochondrial function. This research assessed the mitochondrial energy metabolism of Mstn −/+ KO cells, and wondered whether the mitochondria biogenesis are affected.ResultsIn this study, we successfully achieved Mstn knockout in skeletal muscle C2C12 cells using a CRISPR/Cas9 system and measured proliferation and differentiation using the Cell-Counting Kit-8 assay and qPCR, respectively. We found that MSTN dysfunction could promote proliferation and differentiation compared with the behaviour of wild-type cells. Moreover, Mstn KO induced an increase in KIF5B expression. The mitochondrial content was significantly increased in Mstn KO C2C12 cells, apparently associated with the increases in PGC-1α, Cox1, Cox2, ND1 and ND2 expression. However, no differences were observed in glucose consumption and lactate production. Interestingly, Mstn KO C2C12 cells showed an increase in IL6 and a decrease in TNF-1α levels.ConclusionThese findings indicate that MSTN regulates mitochondrial biogenesis and metabolism. This gene-editing cells provided favourable evidence for animal breeding and metabolic diseases.How to cite: Wang L, Ding Q, Ma S, et al. CRISPR/Cas9-mediated MSTN gene editing Induced Mitochondrial Alterations in C2C12 myoblast Cells. Electron J Biotechnol 2019;40. https://doi.org/10.1016/j.ejbt.2019.03.009  相似文献   

17.
伊犁谷地灰钙土和风沙土剖面特性及生态建设意义   总被引：2，自引：0，他引：2  
西部的生态环境安全关系到国家的生态安全。研究土壤特性及其垂直分布,能对区域生态环境建设和可持续发展提供重要的理论基础和指导。灰钙土与风沙土是新疆伊犁谷地的两种主要土壤类型。本文在对新疆伊犁谷地实地考察基础上,运用42个灰钙土剖面和12个风沙土剖面自然发生层各层的土壤样品测试数据—土壤有机质、pH值、电导率、总盐、八大阴阳离子,研究了灰钙土和风沙土土壤特性的垂直分布,并进行了比较;在此基础上提出区域生态建设中土壤利用和保护的建议。研究表明,伊犁河谷的不同土壤,其土壤特性的垂直分布和变化具有一致性和差异性。一致性体现在有机质和K＋的含量随土壤深度增加而减少,pH值、CO32-、Mg2＋和Na＋的含量随土壤深度增加而增加。差异性体现在两类土壤的有机质、pH值、电导率和总盐在数量上不同。此外,两类土壤的电导率、总盐及SO42-,Cl-,HCO3-,Ca2＋的含量随土壤深度发生变化的趋势不同。  相似文献   

18.
Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls n = 50. Selection criteria—history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired ‘t’ test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) (>2), ALP and GGT compared to controls (P < 0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (P < 0.05). This study suggests that De Ritis ratio >2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratio <1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD.  相似文献   

19.
Oxygen derived free radicals have been implicated in a number of clinical disorders including atherosclerosis (1), ischemic heart disease (IHD) (2), post ischemic reperfusion injury (3) and respiratory distress syndrome (4). These radical are generated by sequential reduction of molecular oxygen; the primary product being superoxide anion (O2 .−) which is subsequently reduced to hydrogen peroxide (H2O2), hydroxy1 radical (OH.) and singlet oxygen (1O2). However the evidence for ODFR induced cell damage in various clinical disorders is still debated and rests largely on free radical scavenging studies, through electron paramagnetic resonance spectroscopic (EPRS) studies have provided direct evidence for ODFR generation following coronary artery ligation (5). By definition, a free radical is an atom, ion or molecule with one or more unpaired electrons (the presence of unpaired electron in a free radical being represented by a superscribed bold dot-R.) and may be formed as a result of homolytic fission of a covalent bond or by electron transfer reactions, and may have cationic (NH3 +), anionic (O2 .−) or neutral (NO) characteristics. The most important in vivo source for these radical species have been found to be univalent biochemical redox reactions involving oxygen. (a) A:B→A.+B. (b) A:+B→A.+B.  相似文献   

20.
The solution of the differential equation y″ + 2Ry′ + n2y = E cos pt is written in a new form which clearly exhibits many important facts thus far overlooked by theoretical and experimental investigators. Writing s = n ? p, and Δn = n ? √n2 ? R2, it is found: (a) When s ≠ Δn, there are “beats,” and the first “beat” maximum is greater than any later maximum while the first “beat” minimum is less than any later “beat” minimum. The “beat” frequency is (s ? Δn)2π. (b) When n2 ? p2 = R2, there are no “beats,” and the resultant amplitude grows monotonically from zero to the amplitude of the forced vibration, (c) At resonance, when n = p, we still have maxima which occur with a frequency Δn2π in a damped system. (d) The absence of “beats” is neither a sufficient nor a necessary condition for resonance in a damped system.In the experimental investigation the upper extremity of a simple pendulum was moved in simple harmonic motion and photographic records obtained of the motion of the pendulum bob. Different degrees of damping were used, ranging from very small to critical.The experimental results are in excellent agreement with theory.  相似文献   

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