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The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases, such as depression and anxiety. Meanwhile, the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor (CB1R), which is strongly expressed in the amygdala of non-human primates (NHPs). However, it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases. Here, we investigated the role of CB1R by knocking down the cannabinoid receptor 1 (CNR1) gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA. We found that CB1R knockdown in the amygdala induced anxiety-like behaviors, including disrupted night sleep, agitated psychomotor activity in new environments, and reduced social desire. Moreover, marmosets with CB1R-knockdown had up-regulated plasma cortisol levels. These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets, and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
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Animales , Callithrix , Receptores de Cannabinoides , Ansiedad , Amígdala del Cerebelo , Cannabinoides , FenotipoRESUMEN
Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2+) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST+), but not protein kinase C-δ-expressing (PKC-δ+), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2+ neurons. The SST+ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST+ GABAergic neurons, but not PKC-δ+ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeASST-DpMeVGLUT2 circuit that regulates licking behavior and promotes water intake.
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Objective:To explore the predictive value of systemic immune-inflammation index (SII) and small and dense low-density lipoprotein-cholesterol (sdLDL-C) on contrast-induced acute kidney injury (CI-AKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI).Methods:This retrospective analysis included 674 STEMI patients who underwent emergency PCI in Affiliated Hospital of Xuzhou Medical University from November 2019 to October 2021, all patients were divided into a training cohort ( n=450) and validation cohort ( n=224) at a ratio of 2∶1 according to the chronological sequence. The patients in the training cohort were further divided into CI-AKI group ( n=92) and non-CI-AKI group ( n=358). Information at admission and emergency blood biochemical indexes were collected, and the SII was calculated. Multifactorial logistic regression analysis was used to explore the independent factors influencing the occurrence of CI-AKI in STEMI patients undergoing emergency PCI in the training cohort and a predictive model was established. Receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test were used to evaluate the model discrimination and calibration. Results:The prevalence of CI-AKI was 20.4% (92/450). Age, proportion of women, sdLDL-C, urea, baseline creatinine, uric acid, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and SII were significantly higher in the CI-AKI group than in the non-CI-AKI group (all P<0.05), and left ventricular ejection fraction (LVEF), high-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR) and lymphocyte count were significantly lower in the CI-AKI group than in the non-CI-AKI group (all P<0.05). The results of multifactorial logistic regression analysis showed that age ( OR=1.046, P=0.001), LVEF ( OR=0.916, P<0.001), sdLDL-C ( OR=4.754, P<0.001), uric acid ( OR=1.012, P=0.007), eGFR ( OR=0.994, P=0.002), and lnSII ( OR=2.471, P<0.001) were independent determinants of CI-AKI after emergency PCI in STEMI patients. ROC curve analysis showed that area under the curve (AUC) for the diagnosis of CI-AKI was 0.688 with a sensitivity of 73.9% and specificity of 61.5% for the SII cut-off point of 1 179.07×10 9/L. The AUC for the diagnosis of CI-AKI was 0.709 with a sensitivity of 65.2% and specificity of 77.4% for the sdLDL-C cut-off point of 1.147 mmol/L. The AUC for the diagnosis of CI-AKI was 0.847 with a sensitivity of 88.0% and a specificity of 70.6% for the combination of SII and sdLDL-C with age, LVEF, uric acid and eGFR. The Hosmer-Lemeshow test (χ2=6.913, P=0.546) proved the goodness of fit of the model. Conclusions:SII and sdLDL-C have significant clinical value in the prediction of CI-AKI. SII and sdLDL-C combined with age, LVEF, uric acid and eGFR could further improve the predictive efficacy of CI-AKI.
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Objective:To investigate whether astaxanthin (AST) down-regulates dynamin-related protein 1 (Drp1) through activating the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway, thereby attenuating contrast-induced acute kidney injury.Methods:Forty adult male Sprague-Dawley rats weighing 160-180 g were randomly divided into five groups: sham surgery group (Sham group), contrast medium injury group (CM group), astaxanthin-intervention group (AST+CM group), SIRT1 inhibitor Ex527 intervention group (Ex527+CM group), and astaxanthin combined with Ex527 intervention group (AST+Ex527+CM group). After 72 hours of modeling, heart blood was removed and kidney tissues were collected for follow-up testing. Serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress-related indexes total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by biochemistry; hematoxylin and eosin staining was performed to observe the pathological changes in the kidney; mitochondrial morphology and number were observed by transmission electron microscopy; reactive oxygen species (ROS) levels were detected by ROS staining in frozen sections; TUNEL staining was performed to detect apoptosis level. The expression levels of SIRT1, p53, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Drp1 and apoptosis-related proteins Bcl-2 and Bax were detected by Western blotting.Results:(1) Compared with the CM group, Scr and BUN level were significantly lower, T-SOD level was higher and MDA level was lower in the AST+CM group, while T-SOD level decreased and MDA level increased after the combination of Ex527 (all P<0.05). (2) ROS expression was lower in the AST+CM group compared to the CM group and higher after the combination of Ex527 (both P<0.05). (3) The number of apoptotic cells was significantly reduced in the AST+CM group compared to the CM group and increased after the combination of Ex527 (both P<0.05). (4) The protein expression levels of SIRT1, PGC-1α and Bcl-2 were increased and the protein expression levels of p53, Drp1 and Bax were decreased (all P<0.05) in the AST+CM group compared with the CM group, and the protein expression levels of SIRT1, PGC-1α and Bcl-2 were decreased and the protein expression levels of p53, Drp1 and Bax were increased when Ex527 was combined (all P<0.05). Conclusion:Astaxanthin can inhibit Drp1-mediated mitochondrial fission by activating the SIRT1 pathway, thereby reducing contrast-induced acute kidney injury in rats.
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Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O
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Animales , Ratones , Cardiomegalia/inducido químicamente , Insuficiencia Cardíaca , Isoproterenol/toxicidad , Mitocondrias , Miocitos Cardíacos/metabolismoRESUMEN
This study is to identify Chinese medicinal materials Rhizoma et Radix Heraclei, Angelicae Sinensis, Radix Angelicae Pubescentis and Rhizoma et Radix Notopterygii based on ITS2 and its secondary structure. Total 26 ITS sequences of 7 species were downloaded from GenBank, the ITS2 sequences were annotated by HMMer method. The NJ phylogenetic tree was built by MEGA software, the intraspecific and interspecific K2P genetic distance were analyzed by MEGA as well. The ITS2 secondary structures of all taxa were predicted by ITS2 database. Sequence matrix of primary structure and secondary structure was aligned by 4Sale software. And the profile neighbor joining (PNJ) phylogenetic tree was constructed via the the ProfDistS software based on the distance method. The results show that, the average interspecific genetic distance was far greater than the average intraspecific genetic distance, an obvious barcoding gap was noted among all taxa; NJ tree showed that all species were clustered into seperate branches; each species had different secondary structures; the PNJ tree showed higher resolution than NJ tree. Therefore, ITS2 is suggested to be used as a barcode for distinguishing the original plants of Rhizoma et Radix Heraclei, Radix Angelicae Sinensis, Radix Angelicae Pubescentis and Rhizoma et Radix Notopterygii in this study, this provides some scientific basis for classification and accurate identification of these Chinese medicinal materials.
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Objective To study the severe fever with thrombocytopenia syndrome bunyavirus (SFTSV)-related vector biological monitoring in Daishan County, Zhoushan Island of Zhejiang Province, and to explore the prevention and control strategies. Methods The monitoring was conducted as follows:squirrel-cage method was used for rodents from 2012 to 2014;the Buqi method for free tick density in villages and towns with confirmed cases in Daishan County from 2015 to 2018;and body surface comb method for parasitic ticks.RT-PCR method was used to detect SFTSV in ticks and rat specimens.Epidemiological survey followed by extensive health education was conducted from 2011 to 2015.Comprehensive health prevention and control measures, such as precision health education and chemical elimination of vectors were taken from 2016 to 2018. Results A total of 327 rodents were captured, including 172 stinking shrews, accounting for 52.60%, and 92 yellow mice, accounting for 28.13%.The main species of ticks was Haematopsus longicortus, accounting for 94.20%.Among them, there were 135 parasitic ticks in three species:Haematopsus longicorum, S.scallopus, and T.nigra. There were 382 free ticks in 6 species, including Haematopsichum longicorum, Sickle fan tick, Hemophilus fannicus, Ixodes ovaliformis, Ixodes granulata, and Ixodes sinensis.From May to October in 2015, the density of field ticks was ≥50 per cloth flag.From May 2016 to 2018, after the elimination application of chemical agents for elimination, the density of ticks was ≤50 per cloth flag.All ticks and rodent specimens tested by RT-PCR were negative for SFTSV.Since precision education in 2016, the awareness rate of SFTS in rural areas has increased from 32.05% to 83.33%.Approximately 70 early warning notices for the epidemic situation were issued in advance.Since 2017, the number of SFTS has been declining year by year, and only 8 cases occurred in 2018. Conclusion In the field environment, chlorothalonil is the dominant mouse species and long horn blood ticks are the dominant ticks.The government leadership, cooperation among departments, technical service provided by professional organization, health education, reduction of tick density in residential environment, timely risk early warning notice, and other comprehensive prevention and control hand strategy all contribute to the achieved result of prevention and control.
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Objective To observe the clinical efficacy of self-prescribed Guchong Decoction combined with Ferroids for the treatment of iron deficiency anemia (IDA)patients with unconsolidation of thoroughfare and conception vessels. Methods A total of 70 IDA patients with unconsolidation of thoroughfare and conception vessels were randomized into treatment group and control group,35 cases in each group. The control group was given oral use of Ferroids, and the treatment group was treated with self-prescribed Guchong Decoction combined with Ferroids. One month constituted a treatment course,and both groups were treated for 2 courses. Before and after treatment,we compared the parameters of blood routine test for red blood cells(RBC),hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC),white blood cells(WBC)and platelets,as well as reticulocytes(Ret)and iron metabolism indexes including serum iron(SI),serum ferritin(SF),and total iron-binding capacity(TIBC). The adverse reaction was monitored during the treatment. After treatment,both western medicine clinical efficacy and traditional Chinese medicine (TCM)syndrome clinical efficacy of the two groups were evaluated. A 3-month follow-up was carried out after treatment to evaluate the recurrence rate. Results(1)Drop-out occurred in one case from the treatment group and in 2 cases from the control group because of short-term medication suspension.(2)After treatment for 2 months, western medicine clinical cure rate of the treatment group was 82.4％ and that of the control group was 60.6％, and TCM syndrome clinical cure rate of the treatment group was 94.1％ and that of the control group was 51.5％,the difference being significant(P < 0.05 or P < 0.01).(3)The levels of RBC,HGB,Ret, MCV, MCH, MCHC, and WBC of the two groups were obviously increased after treatment (P < 0.01), and PLT level was markedly decreased (P < 0.01)as compared with those before treatment,but the inter-group differences after treatment were insignificant (P > 0.05). (4)After treatment,iron metabolism indexes of SF and SI of the two groups were significantly increased (P < 0.01), and TIBC of the treatment group was significantly decreased (P < 0.01). The treatment group had stronger effect on increasing SF and SI and on decreasing TIBC than the control group (P < 0.05 or P < 0.01). (5)The incidence of adverse reaction and the recurrence rate in the treatment group were lower than those of the control group,the difference being significant (P< 0.01). Conclusion Guchong Decoction combined with Ferroids is effective for the treatment of IDA with unconsolidation of thoroughfare and conception vessels through relieving symptoms rapidly, reducing gastrointestinal adverse reaction,and decreasing recurrent rate.
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Objective To explore the association of Lipoprotein-associated phospholipase A2(LP-PLA2) and Antithrombin Ⅲ(AT-Ⅲ)level with the severity of coronary artery lesion in patients with coronary disease. Methods 276 patients undergoing coronary angiography were recruited in the Affiliated Hospital of Xuzhou Medical University from March,2016 to March,2017. Patients were sent to one of the two following groups according to their CAG reports:the controlled group(n=111)and the CAD group(n=165). Gensini scores were calculated in CAD group,and divided CAD group into 4 groups by quartiles:group 1(n=41),group 2(n=39),group 3 (n=42)and group 4(n=43). LP-PLA2 and AT-Ⅲwere then compared in different groups and correlation was analyzed in deciding the severity of coronary artery disease. Results (1)LP-PLA2 level in CAD group was signifi-cantly higher than the controlled group(342.9 ± 91.9 vs. 131.8 ± 27.0,P<0.05),but AT-Ⅲlevel was lower than controlled group and(91.0 ± 12.9 vs. 97.8 ± 11.0,P<0.05).(2)Both LP-PLA2 and AT-Ⅲlevel were different in groups stratified by the quartiles of Gensini scores,and the difference is statistically significant.(3)LP-PLA2 was a risk factor while AT-Ⅲwas a protectional factor for coronary artery disease(OR=1.08,95%CI:1.05~1.11,P<0.01;OR=0.95,95%CI:0.93~0.98,P<0.01;respectively )analyzed by Logisitic regression model.(4)Correla-tion analysis showed a positive association of LP-PLA2 level with Gensini scores(r=0.48,P<0.01),and a nega-tive association of AT-Ⅲlevel with Gensini scores(r=-0.24,P<0.01). Conclusion LP-PLA2 level was higher in CAD patients compared to normal patients ,while the relationship of AT-Ⅲ level among the two groups was reversed. Elevated LP-PLA2 level was associated with the increased severity of coronary artery and can provide guidance for clinic.
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Objective: To explore the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) level, antithrombinⅢ (AT-Ⅲ ) activity and global registry of acute coronary events (GRACE) score in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS); to analyze the predictive value of Lp-PLA2, AT- Ⅲ on risk stratification and nearby risk assessment in NSTE-ACS patients. Methods: Our research included in 2 groups: NSTE-ACS group, n=260 patients with confirmed diagnosis and regular treatment; Control group, n=50 in-hospital patients with coronary angiography excluded coronary artery disease (CAD).plasma level of Lp-PLA2 and AT-Ⅲ activity were examined in the next morning of admission. GRACE score was calculated in NSTE-ACS patients and based on GRACE score, NSTE-ACS group was further divided into 3 subgroups as Low risk subgroup, GRACE score≤108, n=121, Middle risk subgroup, GRACE score (109-140), n=73 and High risk subgroup, GRACE score>140, n=66. The relationships between Lp-PLA2 level, AT-Ⅲ activity and GRACE score were evaluated and the occurrence of major adverse cardiovascular events (MACE) was recorded within 3 months of discharge. Results: ① Compared with Control group, NSTE-ACS group had increased Lp-PLA2 level, P<0.05 and decreased AT-Ⅲ activity, P<0.01. ② In NSTE-ACS group, Lp-PLA2 levels were elevating from Low risk subgroup to Middle risk subgroup and to High risk subgroup accordingly, all P<0.01; compared with Low risk and Middle risk subgroups, High risk subgroup showed decreased AT-Ⅲ activity, P<0.01 and P<0.05; while AT-Ⅲ activity was similar between Low risk and Middle risk subgroups, P>0.05. ③Partial correlation analysis presented that GRACE score was positively related to Lp-PLA2 (r=0.641, P=0.000) and negatively related AT-III (r=-0.179, P=0.006). ④ The area under ROC curve for MACE occurrence in GRACE score was 0.811, in Lp-PLA2 was 0.862 and in AT- Ⅲ was 0.631, all P<0.01; multivariate Logistic regression analysis indicated that Lp-PLA2, GRACE score and HDL-C were the independent predictors for nearby MACE occurrence in NSTE-ACS patients. Conclusion: Blood Lp-PLA2 level and AT-Ⅲ activity were important for risk stratification in NSTE-ACS patients;AT- Ⅲ had less value than Lp-PLA2 and GRACE score for nearby risk assessment.
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The immune system is a complex system involving multiple organs,and it is vulnerable to age,gender,environment and other factors.For a variation normal physiological range,it is a great challenge to evaluate drug-induced immunotoxicity in preclinical safety study.Histomorphologic assessment of the immune system is a recognized cornerstone in the identification of immunotoxicity at present.In this paper,the principles of pathological evaluation for immune system,and pathological evaluation for important immune organs including thymus,spleen,lymph nodes are discussed briefly,so that it is intended to assist toxicity pathologists in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system.
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Objective To investigate the clinical superiority of Chaiqin tiaogan capsule in the treatment of hepatitis B virus.Methods 126 cases of patients admitted to hospital from January 2014 to June 2015 were randomly divided into two groups, the control group (interferon and lamivudine) and the experimental group (interferon, lamivudine and Chaiqin tiaogan capsule), each group of 63 cases.The HBsAg and HBV-DNA negative rate, the changes of liver function and the incidence of adverse reactions in the experimental group were observed and compared.Results The HBsAg negative rate and the HBV-DNA negative rate after treatment three and six months in the control group were significantly higher than the experimental group ( P<0.05).The levels of ALT, AST and DBiL in the control group and the experimental group were significantly decreased, and the levels of ALT, AST and DBiL after treatment six months in the control group were significantly lower than the experimental group ( P <0.05 ) .There were no serious adverse reactions in the control group and experimental group, there was no significant difference between two groups.Conclusion Chaiqin tiaogan capsule can effectively inhibit HBV replication and improve liver function, it has good tolerability and safety applied to clinical.
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Objective To investigate the role of miR-429 in osteosarcoma stem cells.Methods We employed different approaches to test the expression of miR-429 in osteosarcoma stem cells.miR-429-high and miR-429-low cells were separated using molecular probes and their stem cell-like properties were compared.The effect of miR-429 on osteosarcoma stem cell-like properties was further tested through transfection assays.Furthermore,the miR-429 downstream target gene was confirmed by luciferase assay.Results The expression of miR-429 in osteosarcoma stem cells was much lower than that in control cells.miR-429-high cells displayed fewer stem celllike properties than did miR-429-low cells.These observations were confirmed by transfection assays.Additionally,our luciferase assays showed that miR-429 regulates Sox2 at the post-transcriptional level.Conclusion miR-429 negatively regulates osteosarcoma stem celllike properties by targeting Sox2.
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Objective To explore the protective effect and mechanism of astaxanthin (AST) on the acute kidney injury induced by iohexol in rats.Method Thirty rats were randomly divided into five groups:control group (Ctrl);iohexol group (CM);astaxanthin group (AST,100 mg/kg),low astaxanthin dose group (LAST+CM,50 mg/kg) and high astaxanthin dose group (HAST+CM,100 mg/kg),6 in each group.The rats in AST,LAST+CM,HAST+CM groups were administrated with AST by oral gavages using an intubation needle for 10 consecutive days.The rats in Ctrl and CM groups rats in Ctrl,CM groups were given with dissolvant instead in equal volume.Except for the Ctrl and AST groups,on day 8,rats were given indomethacin,L-NAME and iohexol in their femoral vein under chloral hydrate anesthesia to build a contrast induced-nephropathy (CIN) model.At the end of the experiment (72 h after CIN induction),all rats were sacrificed.The Scr level,BUN level,renal histology,renal tissue activities in superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GPx),Glutathione (GSH) and level of malondialdehyde (MDA) were performed.Apoptosis of renal cells was detected by Bcl-2,Bax and Caspase-3 p17 with Western blot.Results Compared with Ctrl group,the levels of Scr,BUN were significantly increased in CM group (all P ＜ 0.01);while compared with CM group,the indicators were decreased in treatment groups (P ＜ 0.01).Renal tubular structure damage,medulla congestion,loss of brush border,vacuolar degeneration,apoptosis and proteinaceous casts were observed in the CM group,and the renal injury scores were higher compared with Ctrl group (P ＜ 0.05),however,administrated with AST could significantly improve the changes (P ＜ 0.05).Oxidative stress indicators showed that MDA level were increased while SOD,GPx,GSH activities were significantly decreased at CM group (all P ＜ 0.05),and the indicators above were ameliorated in treatment groups (all P ＜ 0.05).Western blot showed that the expression of Bcl-2 was down-regulated while the Bax,Caspase 3 p17 was up-regulated respectively at CM group (P ＜ 0.05),while the HAST+CM group could prevent the changes.Conclusions Iohexol can results in oxidative stress increased in kidney,which activate Caspase-3 p17 signal path,down-regulated Bcl-2 expression,up-regulated Bax expression respectively,and lead to cell apoptosis.AST can ameliorate the changes,especially with high AST dose,which suggest that the possible protection mechanism is by ameliorating oxidative stress and inhibiting apoptosis pathways.
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Objective: To investigate the relationship between Bilirubin blood lipid comprehensive index and ifbrinogen (FIB) to severity of coronary lesions in patients with coronary artery disease (CAD). Methods: A total of 324 patients with angiography (CAG) conifrmed diagnosis were divided into 2 sets of groups.①By CAG examination, the patients were divided into 2 groups: CAD group,n=262 and Non-CAD group,n=62.②By Gensini scoring system, the patients were divided into 4 quartile groups: 1st quartile group,n=58, 2nd quartile group,n=110, 3rd group, n=80 and 4th quartile group,n=76. The blood levels of total bilirubin (TBIL), total cholesterol (TC), LDL-C, HDL-C, TG and ifbrinogen were measured and bilirubin blood lipid comprehensive index, TC/(HDL-C+TBIL) and LDL-C/(HDL-C+TBIL) were calculated respectively. Results:①By CAG examination, compared with Non-CAD group, CAD group had increased TC, LDL-C, ratios of TC/(HDL-C+TBIL), LDL-C/(HDL-C+TBIL) and FIB,P Conclusion: Bilirubin blood lipid comprehensive index and ifbrinogen were positively related to severity of coronary lesions in CAD patients.
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<p><b>OBJECTIVE</b>To investigate the effects of curcumin on release of cytochrome c and expressions of Bcl-2, Bax, Bad, Bcl-xL, caspase-3, poly ADP-ribose polymerase (PARP), and survivin of HT-29 cells.</p><p><b>METHODS</b>HT-29 cells were treated with curcumin (0 approximately 80 micromol/L) for 24 h. The release of cytochrome c from the mitochondria and the apoptosis-related proteins Bax, Bcl-2, Bcl-xL, Bad, caspase-3, PARP, and survivin were determined by Western blot analysis and their mRNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Curcumin significantly induced the growth inhibition and apoptosis of HT-29 cells. A decrease in expressions of Bcl-2, Bcl-xL and survivin was observed after exposure to 10 approximately 80 micromol/L curcumin, while the levels of Bax and Bad increased in the curcumin-treated cells. Curcumin also induced the release of cytochrome c, the activation of caspase-3, and the cleavage of PARP in a dose-dependent manner.</p><p><b>CONCLUSION</b>These data suggest that curcumin induced the HT-29 cell apoptosis possibly via the mitochondria-mediated pathway.</p>
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Humanos , Antineoplásicos , Farmacología , Apoptosis , Caspasa 3 , Genética , Metabolismo , Núcleo Celular , Supervivencia Celular , Curcumina , Farmacología , Citocromos c , Secreciones Corporales , Células HT29 , Proteínas Inhibidoras de la Apoptosis , Potencial de la Membrana Mitocondrial , Proteínas Asociadas a Microtúbulos , Genética , Mitocondrias , Fisiología , Proteínas Proto-Oncogénicas c-bcl-2 , Genética , ARN Mensajero , Proteína X Asociada a bcl-2 , Genética , Proteína bcl-X , GenéticaRESUMEN
<p><b>BACKGROUND</b>To summarize the effect of Iressa for refractory patients with advanced non small cell lung cancer (NSCLC) failed to prior chemotherapy.</p><p><b>METHODS</b>Thirty-one patients, with unresectable stage IIIB or IV NSCLC who had disease progression or relapse after prior chemotherapy using platinum-based regimen for at least 2 cycles, were admitted to the Osaka Prefectural Hobikino Hospital. Iressa 250 mg was administered once a day until disease progression was noted. Weekly chest x-ray and monthly CT scan were performed for response assessment each month.</p><p><b>RESULTS</b>Among the 31 patients, one complete response (CR) and 7 partial responses (PR) were observed. CR rate was 3.2% (95% confidence interval: 0-17%), PR rate 22.6% (95% confidence interval: 10%-41%), disease control rate including both tumor responses and stable disease was 80.6% (95% confidence interval: 52%-92%). The rate of symptoms relieves was 51.6% (95% confidence interval: 33%-70%), the most effective symptoms being cough and pain. The median time to improved symptoms was 14 days. The most common adverse events were grade I or II skin rash and diarrhea which were readily manageable and reversible. No patients were withdrawn due to the adverse events</p><p><b>CONCLUSIONS</b>Monotherapy using Iressa is effective and tolerable for the patients with advanced NSCLC who failed prior chemotherapy.</p>