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ObjectiveTo explore the effect of Qishengwan on ileal flora during its treatment of Alzheimer's disease （AD） under the guidance of the theory of "interior-exterior relationship between heart and small intestine". MethodThe AD model was established by bilateral intraventricular injection of β-amyloid 1-42 （Aβ1-42）. The rats were then randomly divided into the blank group， sham-operated group， model group， low-， medium-， and high-dose （5.6， 11.2，22.4 g·kg-1·d-1） Qishengwan groups， and donepezil （0.46 mg·kg-1·d-1） group. After medication for 28 successive days， the spatial memory ability of rats was observed in water maze test， and the levels of Aβ1-42， nuclear transcription factor-κB （NF-κB）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in the hippocampus were analyzed by enzyme-linked immunosorbent assay （ELISA）. Additionally， the contents of the ileum were collected and subjected to 16SrRNA-sequencing analysis for figuring out the changes in ileal flora. ResultCompared with the blank group and sham-operated group， the model group exhibited significantly reduced stay time in the target quadrant and number of target quadrant and platform crossings （P<0.05， P<0.01） and elevated Aβ1-42 content in the hippocampus （P<0.01） and central inflammatory factors NF-κB， TNF-α， and IL-6 （P<0.05， P<0.01）. Compared with the model group， Qishengwan at each dose significantly alleviated the impaired spatial memory function （P<0.05， P<0.01）， improved the deposition of Aβ1-42 in the hippocampus of rats （P<0.05， P<0.01）， and reduced the expression of central nervous system inflammatory factors （P<0.05， P<0.01）， thus exerting a good therapeutic effect on AD rats. The 16SrRNA-sequencing analysis results showed that the structure of the ileal flora in the model group was significantly separated from those in the blank group and sham-operated group. The abundance of Lachnospiraceae NK4A136 group was significantly increased （P<0.01）， while that of Escherichia-Shigella was reduced （P<0.05， P<0.01）. Qishengwan at each dose significantly changed the ileal flora structure and regulated the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae. ConclusionQishengwan has a positive therapeutic effect on AD. It can significantly enhance the memory and cognitive abilities in AD rats， which may be related to its regulation of the structure of rat ileal flora and the relative abundance of Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Ruminococcaceae， the attenuation of the central neuroinflammatory response， and the reduction of central Aβ1-42 deposition.
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Thioredoxin⁃interacting protein (TXNIP), also known as vitamin D3 up⁃regulation protein 1, is named for its ability to bind to thioredoxin (TRX) and inhibit its activity and expression. This article summarizes the discovery and structure of TXNIP, and its effect on the development of prediabetes by regulating the metabolism of glucose and lipid. On this basis, two main pathways of TXNIP participating in the development of diabetes are summarized: TXNIP induces apoptosis of islet cells by antagonizing the anti⁃apoptosis effect of TRX; Over⁃expression of TXNIP promotes the phosphorylation of islet cells and increases the expression of tumor suppressor⁃related protein, which leads to the senescence of islet cells. The role of TXNIP in diabetic complications such as diabetic cardiomyopathy, diabetic diabetic nephropathy and diabetic retinopathy is emphasized. TXNIP can further participate in physiological and biochemical processes such as oxidative stress, autophagy, apoptosis, glucose and lipid metabolism and activation of inflammation through various indirect pathways. Therefore, it is important to understand the mechanism of TXNIP in diabetes mellitus and its complications. Finally, the potential application of TXNIP in diabetes was discussed. Methylation of single TXNIP gene cannot fully reveal the molecular mechanism of diabetes and its complications. In the future, we can study how TXNIP gene interacts with other genes or risk factors, and participates in the occurrence and development of diabetes and its complications. These in⁃depth studies will lay a foundation for the application of target molecules in the diagnosis and treatment of diabetes and its complications.
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It has been found that X-linked inhibitor of apoptosis (XIAP) is the most characteristic and strongest inhibition of apoptosis proteins. The characteristic structures of XIAP are BIR domain and RING domain, which are important structures for XIAP to play an anti- apoptotic role. A variety of endogenous inhibitory proteins (XAF1, SMAC and OMI) can also inhibit XIAP’s anti-apoptotic effect in different ways. XIAP can directly inhibit the initiation and persistence of apoptosis pathway of caspase. XIAP participates in the death receptor pathway and mitochondrial pathway of inhibiting apoptosis in a variety of ways, such as directly binds to caspases, and activates NF-кB way and other signal pathways, which is essential for regulating the survival and development of tumor cells. XIAP is highly expressed in many kinds of tumor tissues. The high expression of XIAP is closely related to the occurrence and development, drug resistance, treatment and prognosis of tumors. XIAP deletion can significantly reduce the tumorigenicity of tumor cells, and XIAP is the downstream factor of cell apoptosis formed by blocking multiple signal pathways. Therefore, XIAP has become a new target for clinical anticancer drug design. At present, three potential directions of XIAP application in clinical treatment of cancer are small molecule inhibitors, antisense oligonucleotide inhibitors and XIAP gene silencing. This paper will introduce the biological function of XIAP against apoptosis and its role in the occurrence and development, drug resistance, treatment and prognosis of tumor diseases.
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Objective::To study the effect of evodia on lipid metabolism and low-density lipoprotein-receptor(LDL-R) mRNA expression in hyperlipidemia mice. Method::Kunming mice (n=80) were randomly divided into normal control group (n=20) and model group (n=60). Serum lipids of the model group were measured after 3 weeks.After successful modeling, the mice can be randomly divided into 5 groups (with 10 in each group): model group (equivalent normal saline), positive control group (simvastatin, 5 mg·kg-1·d-1), drug group (evodia of 5.25, 10.5, 21 mg·kg- 1·d- 1). The mice were given drugs for 3 weeks.Htoxylin-eosin(HE) staining was used to observe the liver cell structure and the change of aortic arch atherosclerosis in the mice.The enzyme linked immunosorbent assay kit was used to test the contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total serum adiponectin (ADPN) in serum of the mice.The expression of LDL-R mRNA in liver of each group was detected by reverse transcription-polymerase chain reaction (RT-PCR). Result::Liver HE staining showed hepatocyte swelling with steatosis in the model group, and alleviated liver steatosis in high-dose, medium-dose evodia and simvastatin groups.HE staining showed damages on the aortict arch wall in the model group, with obvious intima thickening and inflammatory cell infiltration.The intima was thickened obviously in the low-dose group, and the structure of aortic vessel wall was clear in the high-dose group.Compared with the normal group, TC, TG and HDL-C levels in serum of the model group were increased, while HDL-C level was decreased (P<0.01). Serum TC and TG levels of mice in the medium and high-dose groups decreased, whereas LDL-C and HDLl-C levels increased in low, medium and high-dose groups (P<0.05, P<0.01). Compared with the normal group, the adiponectin level in the model group was decreased, while the serum adiponectin levels in medium and high-dose groups were significantly increased (P<0.01). The LDL-R mRNA expression in the liver of mice in the model group was significantly reduced compared with the normal group (P<0.01). The LDL-R mRNA expression in medium and high-dose evodia groups was significantly increased compared with the model group (P<0.01). Conclusion::Evodia can improve the tendency of hepatic lesions and aortic atherosclerosis in hyperlipidemia mice, which may be related to the regulation of adiponectin level, the reduction of lipid content in mice and the up-regulation of LDL-R mRNA expression in mice liver.
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<p><b>OBJECTIVE</b>To observe the changes of electrocardiogram (ECG) and pregnancy outcome of the late pregnancy women.</p><p><b>METHODS</b>Late pregnancy women were divided into two groups by age: over 35 group and under 35 group. The incidence of abnormal electrocardiogram was recorded when the patients were subjected to routine ECG examination. Then the pregnancy, delivery outcome and if there's low birth weight newborn were recorded later.</p><p><b>RESULTS</b>The incidence of abnormal ECG in over 35 group was significantly higher than that in under 35 group (P < 0.05). And the incidence of ST segment changes, arrhythmia in the group of former was higher than that in the group of latter (P < 0.05). Among the different type of arrhythmia, the incidence of sinus bradycardia and ventricular premature beat in the group of former were higher than those in the group of latter (P < 0.05). But the incidence of sinus tachycardia in the former group was obviously lower than that in the latter group (P < 0.05). The incidence of pregnancy loss in over 35 with abnormal ECG group was significantly higher than that in under 35 with normal or abnormal ECG groups (P < 0.05). The incidence of premature birth in over 35 with abnormal ECG group was significantly higher than that in over 35 with normal ECG group (P < 0.05). The incidence of low body weight in over 35 with abnormal ECG group was significantly higher than that in under 35 with normal ECG group (P < 0.05).</p><p><b>CONCLUSION</b>The late pregnancy women with the age of over 35 are more likely to have ECG abnormalities, such as arrhythmia, myocardial ischemia and so on. The older pregnant women with abnormal ECG easily suffer from pregnancy losing, premature birth and having a low birth weight baby.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Age Factors , Arrhythmias, Cardiac , Epidemiology , Electrocardiography , Pregnancy Outcome , EpidemiologyABSTRACT
The aim of the present study is to investigate the change of thioredoxin (Trx) system in myocardial tissue of type 2 diabetic rats after myocardial injury and the underlying mechanism. Adult Sprague Dawley rats were randomly divided into two groups: normal control (NC) group and diabetes (DM) group. Rats in DM group were subjected to high-sugar, high-fat diet and streptozotocin (STZ) injection. Rats in NC group were only given normal diet and equal amount of citric acid buffer injection. At week 1, 2, 4, 12, 21 after STZ injection, plasma glucose concentration and the concentrations of insulin, creatine kinase MB (CK-MB), cardiac troponin I (cTnI) in serum were measured. Myocardial Trx and thioredoxin reductase (TR) activities, as well as caspase-3 activity, were determined by respective assay methods. Protein and mRNA levels of Trx, TR, Trx interacting protein (TXNIP) were determined by Western blot and real time PCR, respectively. The results showed that type 2 diabetic rat model was successfully established at week 1 after STZ injection, and myocardial injury was induced from week 2. Moreover, caspase-3 activity was significantly increased at week 4, 12 in diabetic rats. The activities of myocardial Trx and TR in diabetic rats was decreased from week 2, and continually aggravated as the disease developed. Compared with those in NC group, the mRNA levels of Trx1, Trx2, TR1, TR2 in DM group decreased at week 4, and then increased in week 12. In DM group, the protein levels of Trx1, Trx2, TR1 and TR2 increased significantly at week 12. The mRNA expressions of myocardial TXNIP in diabetic rats were significantly increased at week 4, 12, 24 and protein expression was increased at week 12. These results suggest diabetes can decrease myocardial Trx, TR activity, inducing myocardial cell apoptosis and heart injury. The inhibitory effect of diabetes is mainly associated with TXNIP up-regulation and Trx nitration.
Subject(s)
Animals , Rats , Apoptosis , Carrier Proteins , Metabolism , Caspase 3 , Metabolism , Creatine Kinase, MB Form , Blood , Diabetes Mellitus, Experimental , Diet, High-Fat , Insulin , Blood , Myocardium , Pathology , Rats, Sprague-Dawley , Streptozocin , Thioredoxin-Disulfide Reductase , Metabolism , Thioredoxins , Metabolism , Troponin I , Blood , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of two brain protective methods for aortic operation according to S100beta protein (S100beta) and interleukin-6 (IL-6) in cerebrospinal fluid (CSF).</p><p><b>METHODS</b>From November 2004 to April 2005, 14 patients who underwent aortic operations with circulatory arrest were alternatively allocated to one of two methods of brain protection: only deep hypothermic circulatory arrest (core temperature, 18 degrees C) for descending thoracic aorta operations (group DHCA, n = 5) or selective antegrade cerebral perfusion (core temperature, 20 degrees C; flow rate, 10 ml kg(-1) min(-1)) for aortic arch operations with DHCA (group ASCP, n = 9). Indications for surgical intervention were Stanford type A dissection in 11 patients, Stanford type B dissection in 2 patients, false aneurysm on thoracoabdominal aorta in 1 patient. S100beta and IL-6 in CSF were assayed in all patients from each group before cardiopulmonary bypass, as well as 0, 6, 12, 24, 48, 72 h after the operation.</p><p><b>RESULTS</b>There were no significant differences in lowest core temperature (P > 0.05), hematocrit in lowest core temperature (P > 0.05) and the velocity of rewarming. Mean circulatory arrest time in ASCP group was significant longer than in DHCA group (P < 0.05). There were much more patients with jugular arteries impaired or accompanied with related cerebrovascular diseases in group ASCP compared to group DHCA. The baseline of S100beta in CSF before cardiopulmonary bypass was no difference. S100beta value in CSF ascended to peak level in 12 h after the operation, showing significantly higher in group DHCA than in group ASCP [DHCA vs. ASCP, (0.90 +/- 0.11) microg/ml vs. (0.61 +/- 0.26) pg/ml]. In most hours after operation there was significant intergroup difference. IL-6 value in CSF ascended to peak level in 12 h postoperative for group DHCA and 0 h postoperative for group ASCP. There was no significance difference observed in IL-6 of CSF between two groups except 6 h and 12 h postoperative.</p><p><b>CONCLUSIONS</b>Brain ischemic injury occurred during aortic operations assisted by brain protective methods is not serious. Unilateral ASCP which can delivery adequate oxygen to brain during circulation arrest has some advantage of alleviating ischemic injury compared with only DHCA.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Aortic Aneurysm , Cerebrospinal Fluid , General Surgery , Brain , Circulatory Arrest, Deep Hypothermia Induced , Methods , Interleukin-6 , Cerebrospinal Fluid , Nerve Growth Factors , Cerebrospinal Fluid , Perfusion , Postoperative Period , S100 Calcium Binding Protein beta Subunit , S100 Proteins , Cerebrospinal FluidABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of MMP-2 and MMP-3 in periodontal tissues of rat periodontitis model at different stages of inflammation of varied severity.</p><p><b>METHODS</b>The periodontal tissues were immunohistochemically stained by antibody of MMP-2 and MMP-3.</p><p><b>RESULTS</b>MMP-2 and MMP-3 were both strongly positive in gingival epithelia and fibroblasts in periodontal ligament in rat periodontitis model. And chronic periodontitis showed lower expression of MMP-2 and MMP-3 than that of acute gingivitis and acute peridontitis.</p><p><b>CONCLUSION</b>The expression of MMP-2 and MMP-3 varies in different stage of periodontitis. MMP-2 and MMP-3 may play an important role in development of periodontitis.</p>