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ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 (PbK173)-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free (SPF) male C57BL/6 mice were randomly divided into three groups, with 30 mice each in the control group and PbK173-resistant (PbK173-R) group, and 42 mice in the PbK173-sensitive (PbK173-S) group. Except for the control group, the rest groups were vaccinated with 1×107 PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods (control group, PbK173-R/PbK173-S), dihydroartemisinin (DHA, 40 mg·kg-1) and malaridine (MD, 6 mg·kg-1) were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration (dosing period) and on the fifth day at the end of administration (recovery period), and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods, there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period, there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However, during the recovery period, the red blood cell count, hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group (P<0.05) in the MD group. Compared with that of the control group, the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced (P<0.01), and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group (P<0.01). The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period (P<0.01). The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period (P<0.05). Compared with those in the control group, the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced (P<0.01). Compared with those in the PbK173-R group, the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane, and the erythrocyte flexibility exhibited a decreasing trend in the following order: normal group, PbK173-R group, and PbK173-S group.
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自噬是细胞内一种高度保守的生理过程,可通过溶酶体系统降解过量或受损的细胞器、有毒的蛋白聚集体和病原体等。最新研究表明,海马钙素样1(HPCAL1)可作为特异性自噬受体和铁死亡的正调节因子。HPCAL1可选择性降解钙粘素2(CDH2),加速脂质过氧化,促进癌细胞铁死亡。iHPCAL1是抑制HPCAL1的小分子化合物,可抑制Erastin诱导的肿瘤细胞铁死亡。此外,它还可以抑制铁死亡诱导的急性胰腺炎。本文通过对HPCAL1在铁死亡中的具体作用机制进行概述,为HPCAL1作为铁死亡相关疾病的潜在治疗靶点提供新思路和理论依据。
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Ferroptose , Linhagem Celular Tumoral , AutofagiaRESUMO
@#In this study, in order to overcome the shortcomings of the current methods used to identify Bifidobacterium animalis, such as long time, complicated operation and low adaptability of experimental environment, specific primer probes were designed based on ERIC-PCR technology to identify and detect B.animalis.Based on the genomic DNA of B.animalis HP-B1124, the ERIC-PCR reaction conditions of B.animalis HP-B1124 were optimized, and the ERIC-PCR fragments were obtained one by one and sequenced.Two pairs of specific primer probes were designed.The accuracy, specificity, limitation and universality of the two pairs of primer probes were evaluated, and the two pairs of specific primer probes were used for testing the products containing B.animalis in the commercially published formula.The two pairs of specific primer probes designed in this study could be used for identified strains of B.animalis more simply, quickly and targeted.This method has optimized the current relatively traditional methods of pure culture and plate counting identification of B.animalis, and has solved the high requirements of SNP genotyping technology and real-time fluorescence quantitative PCR method for experimental equipment and reagents in the identification of B.animalis to a certain extent.It has the characteristics of low cost, high specificity and earn a broad market development prospect.
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ObjectiveTo observe the intervention effect of artesunate (ART) and Qingfei Paidu decoction (QFPD) on the mouse model of cytokine storm (CS) induced by viral mimic Poly (I∶C). MethodEighty-four SPF male BALB/c mice were randomly divided into seven groups, with 12 mice in each group. Mice, except for those in the blank group (n=12), were subjected to CS model induction by tail vein injection of Poly (I∶C) at 15 mg·kg-1, followed by drug treatments of low-dose ART (ART-l, 10 mg·kg-1), medium-dose ART (ART-m, 20 mg·kg-1), high-dose ART (ART-h, 40 mg·kg-1), Qingfei Paidu Decoction (QFPD, 2.4 g·kg-1), and dexamethasone (DXM, 10 mg·kg-1). After 6 hours, lung tissues, bronchoalveolar lavage fluid (BALF), spleen, lung, and peripheral blood were collected. The lung and spleen indexes were calculated and the number of inflammatory cells in BALF was detected. The pathological changes in lung tissues were observed by hematoxylin-eosin (HE) staining and the levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and IL-6 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The expression of immune cells in BALF and peripheral blood was detected by flow cytometry. ResultThe analysis of lung and spleen indexes showed that compared with the blank group, the model group showed increased lung and spleen indexes to varying degrees (P<0.05). Compared with the model group, the ART groups showed reduced spleen index (P<0.05) and the ART-l group showed reduced lung index (P<0.05). Additionally, the QFPD group showed reduced lung and spleen indexes (P<0.05). ELISA results showed that except for TNF-α, the levels of IFN-γ, IL-1β, and IL-6 in the model group increased compared with those in the blank group (P<0.05). Compared with the model group, the ART-l group and the QFPD group showed reduced content of TNF-α (P<0.05), and all groups with drug intervention showed reduced content of IFN-γ, IL-1β, and IL-6 (P<0.05). The number of inflammatory cells in BALF showed a downward trend in the model group, and the number of cells increased in the groups with drug intervention except for the DXM group (P<0.05). Flow cytometry showed that compared with the blank group, the model group showed decreased number of CD3 in the peripheral blood (P<0.05), increased Ly-6G and F4/80 (P<0.05), decreased expression of CD45, CD3, and F4/80 in BALF (P<0.05), and increased expressions of Ly-6G (P<0.05). Compared with the model group, the ART groups and QFPD group showed increased CD45 content in peripheral blood (P<0.05), decreased Ly-6G and F4/80 content (P<0.05), increased CD45 and F4/80 content in BALF (P<0.05), and decreased expression of Ly-6G (P<0.05). ConclusionART and QFPD have a good protective effect on Poly (I∶C)-induced CS in mice, and the mechanism is related to the effective intervention in immune cell disorder.
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Chimeric antigen receptor T-cell (CAR-T) is one of the effective methods for treatment of lymphoma. The way to improve the efficacy and control the reverse reactions still needs to be explored further. Several clinical trials have indicated CAR-T could have favorable effects on the B-cell lymphoma patients with controllable reverse reactions. However, antigen loss is a major factor for the acquired resistance to CD19 CAR-T therapy. Other clinical researches, including CD22 for treatment of B-cell lymphoma and CD30 for Hodgkin lymphoma, have increased the efficacy of CAR-T. Moreover, lots of trials have suggested that the patients who received cyclophosphamide or bendamustine plus fludarabine lymphodepletion can get a high effective rate.
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Objective Analysis and adscription of volatiles from Guizhi Tang and study on its improvement of the learning and memory in dementia mice induced by scopolamine.Methods The volatile oil from Guizhi Tang(GZT),Guizhi and Shengjiang was extracted using steam distillation method and was analyzed by GC-MS. Morris water maze and step-down test were carried out for obtain the difference of the learning and memory improvement in 40 ICR mice from randomized groups, such as the control group, the model group, the donepezil group (2 mg/kg), the low dose of volatile oil of GZT (5 mg/kg), and the high dose of volatile oil of GZT (20 mg/kg), and ACh, AchE, BchE and chE in serum were detected by ELISA. Results Among 38 identyfied volatile ingredients from GZT, 18(44% in weight) was from Guizhi, and 9 was from Shengjiang. Compared with the model group, the low and high dose of GZT volatile oil significantly increased swimming distance ratio in destination quadrant (26.74% ± 16.42%vs.9.42% ± 8.50%, P<0.05); goal quadrant time scale (43.51% ± 25.12%vs. 14.50% ± 12.23%,P<0.05)) increased significantly than the model group ; the number of errors in the experiment platform (1.63 ± 1.19vs. 0.25 ± 0.46, P<0.05) obviously increased than model group ; platform test in the made errors times (0.57 ± 0.98vs. 4.43 ± 2.4, P<0.05) significantly reduced. The GZT total volatile oil groups significantly reduced cognitive obstacles small rat serum in the cholinester enzyme (chE) (140.90 ± 3.27, 144.79 ± 6.71vs. 134.49 ± 3.36,P<0.05); acetylcholinesterase (AchE) (3.30 ± 1.31, 3.94 ± 0.78 vs.8.52 ± 3.39,P<0.05); butyrylcholinesterase (BchE) (3.22 ± 0.45, 3.66 ± 0.53vs. 7.99 ± 0.79,P<0.05); and acetylcholine (Ach) (4.10 ± 0.38, 3.03 ± 0.25vs.1.72 ± 0.50, P<0.05) significantly increased.Conclusions The GZT volatile oil mainly from Guizhi and Shengjiang can improve the learning and memory ability in dementia mice induced by scopolamine via a cholinergic mechnism.
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Objective:To observe the effects of FNS007 on collagen Ⅱ-induced arthritis(CIA) rat models and investigate the underlying mechanism.Methods: CIA model was induced by intradermal injection of Freunds adjuvant and bovine CⅡ.Rats were randomly divided into six groups:normal control group,model group,methotrexate group,high,middle and low doses of FNS007 groups,with 12 rats in each group.FNS007 was gived by intravenous injection,the normal control and model group were administrated with PBS.Observing the paw thickness,ankle joint width and the arthritis scores in the CIA rats during the experiment.On d 22 after injection of the drug, all rats were killed.Interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6) and level of anti-CⅡantibody in serum were examined by enzyme-linked immunosorbent assay (ELISA).The pathological score and radiography of ankle joint were evaluated.Results: Data revealed that FNS007 treated groups showed a significant reduction in paw thickness,ankle joint width and the arthritis scores compared to model group (P<0.05,P<0.01),especially FNS007 high dose goup.The levels of TNF-α,IFN-γ,IL-6 and anti-CⅡantibodies in serum in high dose goup were significantly lower than those of model group(P<0.05,P<0.01).X-ray examination showed that FNS007 could significantly alleviate the damage of joint and decrease the radiographic scores.Pathological examination exhibited that FNS007 could significantly reduce pathological scores,alleviate inflammatory cell infiltration and synovial hyperplasia,improve the histopathological changes.Conclusion: FNS007 has a treating effect on CIA rats,and the mechanisms may be through competitive inhibition of T cell,inhibiting inflammatory cytokines and anti-CⅡantibodies secretion,regulating the abnormal immune responses.
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Aim To investigate the effect of non-T cell binding peptide(FNS007)on collagen type Ⅱ-induced arthritis(CIA)in mice and the possible mechanisms.Methods The CIA model was induced by intradermal injection of bovine CⅡ+Freunds adjuvant.At the clinical onset of CIA,mice were randomly divided into 6 groups: blank control group(Control),model group,ORENCIA(abatacept)group,FNS007 low dose(1.2 mg·kg-1)group,FNS007 middle dose(2.4 mg·kg-1)group and FNS007 high dose(4.8 mg·kg-1)group.FNS007 was given by intravenous injection on the first day of arthritis and every other day until the study was terminated on d 28 after injection of the drug.The paw thickness and the ankle joint width were measured,and the arthritis scores were recorded.At termination,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and level of anti-CⅡ antibody in serum were examined by enzyme-linked immunosorbent assay(ELISA).Bone injury was analyzed by X-ray imaging,and HE staining was conducted to observe the histopathologic changes and pathological score of ankle tissues.Results CIA models were successfully induced.Compared with CIA group,FNS007 high dose significantly reduced the paw thickness and the ankle joint left-right diameter,lowered arthritis scores in CIA mice,reduced serum concentrations of IFN-γ,IL-6 and anti-CⅡ antibodies,and lowered the radiographic and histologic scores.Compared with CIA group,FNS007 middle dose group showed marked reduction in the arthritis scores,IL-6 content in serum,and inhibion in the radiographic and histologic scores.The arthritis scores,concentration of IFN-γ,the radiographic and histologic scores were significantly reduced in FNS007 low dose group compared with those in model group.Conclusion FNS007 can effectively inhibit the progression of CIA through inhibiting T-cell activation and reducing inflammatory cytokines,anti-CⅡ antibodies,and histoclasia and bone destruction.
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Objective To study the clinical features, effects of therapeutic regimen and prognosis of patents with mantle cell lymphoma (MCL). Methods Clinical data of 27 MCL patients admitted in Tianjin Medical University Cancer Institute&Hospital from January 2008 to December 2014 were retrospectively analyzed. Cox regression analysis was used to analyze influencing factors of prognosis of MCL. Results The median age was 68 years old for 27 patients, and the male-to-female ratio was 4.4∶1. Ann Arbor staging showed that 25 cases were stageⅢ-Ⅳ(92.6%), 8 cases were heptosplenomegaly (29.6%), 7 cases showed extranodal involvement (25.9%). ECOG scoring showed that 4 cases with scores of 2-4 (14.8%), 8 cases were 0-3 (29.6%), 14 cases were 4-5 (51.9%) and 5 cases were 6-11 (18.5%). The Ki-67 index≤30%was found in 9 cases (33.3%), and>30%was found in 18 cases (67.7%). Patients with B symptom was found in 10 (37.0%). The elevated lactate dehydrogenase (LDH) was found in 17 cases (63.0%). The increased Beta 2- microglobulin was found in 8 cases (29.6%). Seven patients were found with bone marrow involvement. The total effective rate (ORR) was 81.8%in group with R-CHOP method, and the ORR was 68.8%in group with CHOP method. Multivariate analysis showed that age, LDH and Ki-67 were independent factors influencing the prognosis of MCL (P60 years, elevated LDH and Ki-67 index>30%are with poor prognosis.
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Objective To investigate the relationship between Sfrp5 and T2DM macroangiopathy , and to evaluate the activation of calcium dobesilate. Methods T2DM patients were divided into experimental group (IMT≥0.90 mm,n = 65)and control group (IMT 0.05). IMT in group A were decreased when compared with group B (P < 0.05). Conclusion Sfrp5 is negatively correlated with macroangiopathy. Calcium dobesilate can elevate Sfrp5 and IL-10,thus delay the progression of macroangiopathy.
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Objective To observe the effects of Jieyu-Chufan capsule(JCC) on the behavior and the monoamine neurotransmitter content of cerebral in depression mouse model and explore its mechanism. Methods The ICR male mouse were randomly divided into seven groups according to their weights(the model group, the low, middle and high doses group, Baiyoujie group, the amitriptyline group, the normal control group). The low, middle and high doses group were given JCC with 1.250, 2.500, 5.000 g/kg separately by intragastric administration. Baiyoujie group was given 0.014 g/kg Baiyoujie by gavage. The amitriptyline group was given 0.050 g/kg amitriptyline by gavage. The model group and the normal control group received the same volume of distilled water intragastrically. The drugs were administrated once a day. The brepharoptosis and movement conditions of mouse were observed after 22 days. The monoamine neurotransmitter content of each group was measured after 25 days. Results Compared to the model group, the number of mouse with brepharoptosis decreased in the high dose group after 1, 2, 6 hour with reserpine injection (P<0.05 or P<0.01);the number of mouse came out from the circle increased after 4 hours with reserpine injection (P<0.05 or P<0.01);the content of NA (880.45 ± 428.81 ng/g, 875.98 ± 449.33 ng/g vs. 299.92 ± 267.08 ng/g) and DA (2 305.99 ± 530.37 ng/g, 2 169.99 ± 278.19 ng/g vs. 1 439.34 ± 357.33 ng/g) in the middle and high dose group increased (P<0.01);the content of 5-HT (781.43 ± 135.10 ng/g vs. 492.01 ± 192.80 ng/g) in the middle group increased (P<0.01). Conclusions JCC showed an antidepression influence in depression mouse model induced by reserpine. The mechanism may be related to regulating the level of monoamine neurotransmitter in the nervous centralis .
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The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.
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Humanos , Regiões 3' não Traduzidas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Linfoma Difuso de Grandes Células B , Genética , Metabolismo , Terapêutica , MicroRNAs , Genética , Metabolismo , Proteínas Proto-Oncogênicas c-bcl-6 , GenéticaRESUMO
OBJECTIVE:To establish a method for the contents determination of 9 components in Guizhi decoction,and com-pare the effects of traditional decoction method and the extracting machine decoction method on these contents in Guizhi decoction. METHODS:HPLC was performed on the column of Agilent Zorbax SB-C18 with mobile phaseof acetonitrile- 0.1% phosphoric ac-id(gradient elution)at a flow rate of 1.0 ml/min,the detection wavelength was 230 nm,254 nm and 280 nm,the column tempera-ture was 25℃,and the injection volume was 10μl. RESULTS:The linear range was 0.410 2-210.0μg/ml for gallic acid(r=0.999 9), 0.994 0-254.5μg/ml for albiflorin(r=0.999 9),1.636 0-1 675.0μg/ml for paeoniflorin(r=0.999 9),0.988 3-506.0μg/ml for liquiri-tin(r=0.999 6),0.987 3-31.59 μg/ml for coumarin(r=0.999 5),0.486 8-124.6 μg/ml for cinnamic acid(r=0.999 5),2.458 0-314.6μg/ml for cinnamaldehyde(r=0.999 5),0.034 3-1.096 μg/ml for 2-methoxy cinnamaldehyde(r=0.999 8),and 1.711 0-219.0 μg/ml for glycyrrdhizic acid (r=0.999 7);RSDs of precision,stability and reproducibility tests were lower than 5%,recoveries were 93.56%-103.19%(RSD=4.00%,n=9)、101.51%-107.32%(RSD=2.21%,n=9)、95.08%-103.76%(RSD=2.87%,n=9)、100.82%-105.73%(RSD=1.85%,n=9)、85.08%-89.12%(RSD=1.40%,n=9)、92.31%-99.12%(RSD=2.71%,n=9)、99.17%-102.32%(RSD=1.24%,n=9)、100.15%-103.98%(RSD=1.18%,n=9)、99.93%-102.61%(RSD=1.03%,n=9). The content of total effective components from the extracting machine decoction method was 4 565μg/g,that from the traditional decoc-tion method was 2 742 μg/g.CONCLUSIONS:The method is simple,stable and reproducible,and can be used for the simultaneous determination of 9 componentsin Guizhi decoction. The contents of gallic acid,albiflorin and 2-methoxy cinnamaldehyde are first re-ported. The total effective components from the extracting machine decoction method are higher than that from the traditional decoc-tion method.
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Objective To investigate effects of H2 S on myocardial ischemia injury in rats and explore the possible mechanism from oxidative stress.Methods Fourty-eight male SD rats were randomly divided into 6 groups:sham operation group,ischemia group,ischemia + NaHS low,middle and high dose groups and ischemia + PPG group.The acute myocardial ischemia model was established by ligating the left anterior descending coronary artery(LAD) of the rats.Saline was intraperitoneally administrated in ischemia group.LADs were not ligated but only threaded in sham operation group in rats.In ischemia + NaHS low,middle and high dose groups or ischemia + PPG group,sodium hydrosulfide(NaHS) or DL-propargylglycine(PPG) was intraperitoneally injected respectively at 3 hours after ischemia.All rats were killed at 6 hours after the operation.The content of malondialdehyde (M DA),and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in myocardial tissue were respectively measured.The pathological changes of myocardial tissue were observed with electron microscope.Results Compared with those of sham operation group,the myocardial structural damage was increased,the content of MDA was significantly increased,and the activities of SOD and GSH-Px were significantly decreased in ischemia group in rats ((P < 0.01).Compared with those of ischemia group,the myocardial structural damage was alleviated,the content of MDA was significantly decreased,and the activity of SOD was significantly increased in ischemia + NaHS low,middle and high dose groups ; the activity of GSH-Px was significantly increased in ischemia + NaHS middle and high dose groups in rats (P < 0.05).Compared with those of ischemia group,the myocardial structural damage was increased,the content of MDA was increased,the activities of SOD and GSH-Px were decreased in ischemia + PPG group in rats (P < 0.05).Conclusion The administration of H2S could significantly alleviate the myocardial injury by increasing the activities of SOD and GSH-Px,and decreasing the MDA synthesis in acute myocardial ischemia.
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Objective To evaluate the effects of exogenous hydrogen sulfide on inflammatory responses during acute myocardial ischemia in rats.Methods Twenty-four adult male Sprague-Dawley rats,weighing 250-290 g,were randomly divided into 3 groups (n =8 each):sham operation group,acute myocardial ischemia group,and sodium hydrosulfide (NaHS) group.The animals were anesthetized with intraperitoneal chloral hydrate.The model of acute myocardial ischemia was established by ligating the left anterior descending branch of coronary artery.Normal saline 2 ml/kg and NaHS 3.12 mg/kg were intraperitoneally injected at 3 h of ischemia in AMI and NaHS groups,respectively.The rats were sacrificed at 6 h after ligation and hearts were removed for determination of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) contents (by ELISA) and intercellular adhesion molecule-1 (ICAM-1) mRNA expression (by semi-quantitative PCR) in myocardial tissues and for examination of myocardial ultrastructure with transmission electron microscope.Results Compared with S group,IL-1β,IL-6 and TNF-α conte.nts and ICAM-1 mRNA expression in myocardial tissues were significantly increased in AMI group (P < 0.05).Compared with AMI group,IL-1β,IL-6 and TNF-α contents and ICAM-1 mRNA expression in myocardial tissues were significantly decreased in NaHS group (P < 0.05).The damage to myocardial ultrastructure was significantly alleviated in NaHS group when compared with AMI group.Conclusion The mechanism by which exogenous H2S alleviates the acute myocardial ischemia injury is related to inhibition of the inflammatory responses in rats.
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<p><b>OBJECTIVE</b>The aim of the present study was to evaluate the modulating effect of glycyrrhizic acid C-18 epimers, 18alpha-glycyrrhizic acid (alpha-GL) and 18beta-glycyrrhizic acid (beta-GL) on both P-glycoprotein (P-gp) activity and expression in Caco-2 cell.</p><p><b>METHOD</b>The effects of P-gp activity were analyzed by rhodamine (Rhd 123) accumulation test, and those of P-gp expression were analyzed by flow cytometry and real-time PCR.</p><p><b>RESULT</b>At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL inhibited the function of P-gp and with on dose dependent while beta-GL induced the function of P-gp at three test concentrations with no dose dependent too. At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL down-regulated the expression of MDR1 mRNA. At high concentrations (60 micromol x L(-1)), beta-GL up-regulated the expression of MDR1 mRNA; At high concentrations (60 micromol x L(-1)), beta-GL induced the expression of P-gp protein while alpha-GL has no effect on the expression of P-gp protein at three test concentrations.</p><p><b>CONCLUSION</b>The effects of alpha-GL and beta-GL on the expression of MDR1 mRNA and CYP3A mRNA showed the same trend. The character that epimers of GL act on CYP3A and P-gp show similar stereo selectivity whether relate to PXR need further study.</p>
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Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Genética , Metabolismo , Células CACO-2 , Regulação para Baixo , Medicamentos de Ervas Chinesas , Farmacologia , Expressão Gênica , Ácido Glicirrízico , Química , FarmacologiaRESUMO
Cinnamaldehyde was shown to have significant anti-inflammatory and anti-pyretic actions in studies from both others' and our lab. Prostaglandin E2 (PGE2) plays a key role in generation of these pathological states, while PGE, synthase-1 (mPGES-1) is one of crucial biological elements in the process of PGE2 production. And as a downstream inducible terminal prostaglandin synthase of COX-2, mPGES-1 is now regarded as a more promising novel drug target than COX-2 and is attracting more and more attention from both academia and pharmaceutical industry. The purpose of present study was to further investigate the anti-inflammatory and antipyretic molecular mechanisms of cinnamaldehyde based on the mouse macrophage cell line RAW264. 7 in vitro. The PGE2 was identified by using the method of enzyme-linked immunosorbent assay (ELISA) and the expression of COX-2 and mPGES-1 at mRNA and protein levels was detected by the Real-time PCR and Western blotting methods respectively. The experimental results suggested that cinnamaldehyde could evidently reverse the increased production of PGE2induced by IL-1beta. Moreover, the up-regulated expression levels of mPGES-1 and COX-2 were significatly decreased. Together, these results provide compelling evidence that the down-regulated actions to both the production of PGE2 as well as the expression of mPGES-I might account for, at least in part, the anti-inflammatory and anti-pyretic effects of cinnamaldehyde.
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Animais , Camundongos , Acroleína , Farmacologia , Western Blotting , Linhagem Celular , Dinoprostona , Metabolismo , Interleucina-1beta , Farmacologia , Oxirredutases Intramoleculares , Metabolismo , Macrófagos , Metabolismo , Prostaglandina-E Sintases , Reação em Cadeia da Polimerase em Tempo RealRESUMO
ObjectiveTo evaluate the effect of aminooxyacetic acid on focal cerebral ischemia injury in rats.MethodsEighty healthy male SD rats aged 2.5 month weighing 250-280 g were randomly divided into five groups( n = 16 each):sham operation group(group S),cerebral ischemia group(group Ⅰ),aminooxoacetic acid low,medium and high dose groups(groups AL,AM and AH ).Focal cerebral ischemia was induced by occlusion of middle cerebral artery using a nylon thread with rounding tip which was inserted into right internal carotid artery in groups I,AL,AM and AH.Intraperitoneal amincoxoacetic acid 25,50 and 100 μmol/kg were administered at 3 h of ischemia in groups AL,AM and AH respectively,while equal volume of normal saline 1 ml/kg were injected in groups S and I.Neurological function was assessed and scored (0= no deficit,4= unable to move,unconscious) in 8 rats at 21 h after aminooxyacetic acid administration in each group.The animals were then sacrificed and the brains were removed for determination of the cystathionine beta-synthase (CBS) activities in cortex,hippocampus and striatum corpora.The other eight rats of each group were sacrificed at 21 h after amincoxoacetic acid administration for determination of the cerebral infarct volume.ResultsCompared with group S,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly increased,the infarct volumes were significantly enlarged in group Ⅰ ( P < 0.05).Compared with group Ⅰ,the neurological deficit scores and the CBS activities in cortex and hippocampus were significantly decreased,the cerebral infarct volumes were significantly reduced in groups AM and AH (P < 0.05).There was no significant difference in the above-mentioned variables between groups AL and Ⅰ.ConclusionAminooxoacetic acid can reduce focal cerebral ischemia injury by decreasing CBS activity and reducing H2 S production in rats.
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Clinical data of 13 patients with primary pulmonary lymphoma(PPL),treated in Tianjin Medical University Cancer Hospital from January 1999 to December 2009,were retrospectively reviewed.There were 8 patients with mucosa-associated lymphoid tissue(MALT)marginal zone lymphoma,2 patients with diffuse large B cell lymphoma,1 patient with NK/T cell lymphoma,1 patient with nodular sclerosis Hodgkin's lymphoma,and 1 patients with lymphocytic predominance Hodgkin's lymphoma.The main clinical symptoms were cough,fever,night sweat and weight loss.Two patients did not have any symptoms.Pulmonary consolidation shadows and multiple nodules were the main findings of CT scan.An air bronchogram was often seen in the consolidation imaging.The overall 5-year survival rate was 9/13 for all patients;while that was 7/8 for MALT marginal gone lymphoma.
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<p><b>OBJECTIVE</b>To study the effects of the ingredients from Chinese herbs with the nature of cold or hot on the expression of TRPV1 and TRPM8.</p><p><b>METHOD</b>The effects of ingredients from herbs on primary culture DRG neurons are observed in vitro. The expression quantity of gene is detected by the method of real time PCR. the 2 (-deltadeltaCT) method is applied to analyze the data.</p><p><b>RESULT</b>Ingredients from herbs with the nature of cold up-regulate the expression level of TRPV1 and down-regulate that of TRPM8, especially under the temperature condition of 39 degrees C; while ingredients from herbs with the nature of hot up-regulate the expression level of TRPM8 and down-regulated that of TRPV1, which is more significant under the temperature condition of 19 degrees C.</p><p><b>CONCLUSION</b>The regulatory changes of TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be related to the cold and hot natures of the herbs from which the ingredients are extracted. And this could be one of the therapeutic mechanisms for the treatment of Chinese herbal medicines to cold- and heat-related diseases.</p>