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1.
Acta Pharmacol Sin ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776448

RESUMO

Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg-1· d-1, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8-16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen-glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1678-1681, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607331

RESUMO

OBJECTIVE: To analyze the diagnostic value of (1, 3) -ß-D-glucan and galactomannan (GM) tests in the patients with acute leukemia complicated by invasive fungal disease, and explore the application of serological detection (G/GM) and lung CT for early diagnosis of invasive fungal disease (IFD). METHODS: A total of 493 patients with acute leukemia complicated by high risk invasive fungal infection, also receival G and GM tests, in Department of hematology of our hospital from June 2016 to December 2016 were selected and were divided into IFD-confirmed group (62 cases) including confirmed and clinical diagnesed IFD, and IFD-unconfirmed group (431 cases) including suspected IFD and non-IFD according to the diagnostic criteria of IFD. The results of G and GM tests in patients of 2 groups were analyzed, then the diagnostic efficacy of G and GM done and combination evaluated. In addition, 26 patients whose lung CT negative at hospitalization, moreover, presentation of changes in lung by CT during hospitalization and serological G and GM test positive were selected, and the difference of time between serological that postive and presentation of changes in lung by CT were compared for the estimation of early diagnotic value. RESULTS: The positive rate of (1, 3) -ß-D-glucan in IFD-confirmed group and IFD-unconfirmed group was 56.5% and 10.4%, respectively. Meanwhile, that of galactomannan test was 41.9% and 9.0%, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of (1, 3) -ß-D-glucan was 56%, 90%, 44% and 92%, and that of galactomannan was 42%、91%、40% and 93%, respectively. Moreover, the combination of (1, 3) -ß-D-glucan and galactomannan could raise the sensitivity to 69% and specificity to 98%. The positive results of serological detection (G/GM) come earlier about five days than CT changes. CONCLUSION: Both (1, 3) -ß-D-glucan and galactomannan test have high sensitivity and specificity, and the combination of them can improve the diagnostic efficacy, and make the clinical antifungal therapy more precisely. In the early clinical diagnosis of IFD, the positive results of serological detection coming earlier than lung CT.


Assuntos
Infecções Fúngicas Invasivas , Leucemia Mieloide Aguda , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/etiologia , Leucemia Mieloide Aguda/complicações , Mananas
3.
Biomed Pharmacother ; 118: 109389, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545275

RESUMO

The current treatment for diabetic nephropathy (DN) is still limited. NaoXinTong Capsule (NXT) is a Chinese Medicine prescribed to patients with cardiovascular disease. It can also ameliorate metabolic syndromes in patients indicating its anti-diabetic properties. Herein we report the therapeutic effects of NXT on the developed DN. The db/db diabetic mice at ˜12 weeks old, the age with DN at middle/advanced stages, were treated with NXT for 12 weeks. We found NXT treatment reduced diabetes-induced hyperglycemia and dyslipidemia, thereby substantially reduced DN progress. In the kidney, NXT reduced mesangial matrix expansion and glomerulosclerosis by inhibiting extracellular matrix accumulation through activation of matrix metalloproteinase 2/9 and inactivating transforming growth factor ß1 expression. NXT reduced podocyte injury by reducing renal inflammation and expression of adhesion molecules. Mechanically, NXT potently activated AMPKα in multiple tissues thereby enhancing energy metabolism. In the liver, NXT increased glucokinase expression and insulin sensitivity by increasing insulin receptor substrate 1/2 and protein kinase B (AKT) 1/2 expression/phosphorylation. In skeletal muscle, NXT activated expression of glucose transporter type 4, AKT, glycogen synthase and peroxisome proliferator activated receptor α/γ. In adipose tissue, NXT reduced fatty acid synthase while activating hormone-sensitive lipase expression. Taken together, our study demonstrates that NXT reduced progress of the developed DN by ameliorating glucose, lipid and energy metabolism, maintaining renal structural and functional integrity. Our study also indicates the potential application of NXT for DN treatment in clinics.

4.
Biomed Pharmacother ; 118: 109270, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401394

RESUMO

The landscape of cellular plasticity and sources with relevant niche signals in hepatocellular carcinoma is still obscure. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is involved in a variety of malignancies and overexpressed in hepatocellular carcinoma (HCC). We have investigated the role of TRPV1 in HCC from different angles by various experimental techniques, such as in vivo and in vitro experiments, and by bioinformatics analysis of data from genetic models induced by diethylnitrosamine (DEN), mice samples and human HCC samples. We find that TRPV1 knockout promotes to hepatocarcinogenesis and deconstructs the portal triad adjacent to tumor border that is contributed by originations of tumor initiating cells and biliary cells. Epithelial to mesenchymal transition (EMT) is involved and transcription factors Ovol2 and Zeb1 coordinated with Sox 10 drive gene expression in the event which is also confirmed by the expression of these proteins in human HCC samples. Treatment with TRPV1 agonist Capsaicin inhibits the growth of HCC cells in xenograft models. Our findings demonstrate that TRPV1 is a potential therapeutic target in human HCC and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10.

5.
Pharmacol Res ; 144: 167-180, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30986544

RESUMO

Formation of thrombosis is associated with activation of platelets and endothelial cells. The effect of LongShengZhi Capsule (LSZ), a traditional Chinese medicine used for treatment of vascular diseases, on thrombosis was investigated in this study. BALB/c mice were induced thrombosis by injection of carrageenan while receiving pre or simultaneous LSZ treatment. We also compared the therapeutic effects of LSZ and clopidogrel on formed thrombi. LSZ inhibited carrageenan-induced thrombi in mouse tissue vessels. In addition, LSZ but not clopidogrel reduced formed thrombi with a short time window. The reduction of thrombi by LSZ was associated with reduced serum P-selectin, reduced expression of TNF-α and P-selectin and activated matrix metalloproteinase 2 expression in tissues. In vitro, LSZ decreased thrombin-induced human platelet clot retraction which was associated with inactivation of AKT and ERK1/2. LSZ also reduced adhesion of platelets or THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein or lipopolysaccharide. The anti-adherent actions of LSZ was attributed to reduction of oxidative stress, expression of platelet receptors (P2Y12, PAR4 and CD36) and AKT activity in platelets. LSZ also reduced adhesion molecules or tissue factor but activated tissue factor pathway inhibitor expression in HUVECs. Taken together, our study demonstrates the antithrombotic properties of LSZ by reducing activation of platelets and endothelial cells, and suggests its potential application in clinics.

6.
World Neurosurg ; 127: e22-e29, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30790734

RESUMO

OBJECTIVE: Lymphocytic hypophysitis (LYH) is a rare autoimmune inflammatory disease of the pituitary gland. In this study, we aim to characterize LYH at presentation and focus on the management and prognosis of LYH. METHODS: A retrospective study of patients with LYH was conducted between 2011 and 2018 at a single institute. The patients were included by pathologic conformation and strict exclusion criteria. Clinical profile, imaging, and management data were collected. RESULTS: Twenty patients with LYH (16 women and 4 men) were included. Ten patients were diagnosed histologically and the remaining 10 patients were confirmed clinically of exclusion criteria. The median age at diagnosis was 37 years (range, 16-58 years). Presenting symptoms were followed by polyuria/polydipsia (11, 55%), vision changes (10, 50%), headache (8, 40%), menstrual irregularities and amenorrhea (4, 20%), diplopia (1, 5%), or sexual dysfunction (1, 5%). Eight patients had partial anterior pituitary hormone dysfunction. The thyroid-stimulating hormone axis was most involved. Ten patients received transsphenoidal surgery, 5 patients experienced steroid pulse therapy, and observation was performed on 5 patients. Only 5 patients (25%) showed improvement of anterior pituitary dysfunction after initial management. Recovery of diabetes insipidus occurred in 2 patients (18%). The overall recurrence rate was 22.2%. CONCLUSIONS: Nonoperative treatment is a better option for most patients with LYH because it is effective and noninvasive. Surgery is recommended for definitive diagnosis, severe or rapid progression of neurologic impairment, and glucocorticoid insensitivity. Periodic follow-up is mandatory in a patient's long-term management.


Assuntos
Hipofisite Autoimune/patologia , Imagem por Ressonância Magnética , Neuroimagem , Adolescente , Adulto , Hipofisite Autoimune/complicações , Hipofisite Autoimune/diagnóstico por imagem , Hipofisite Autoimune/terapia , Terapia Combinada , Diabetes Insípido/etiologia , Diagnóstico Diferencial , Diplopia/etiologia , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Hemianopsia/etiologia , Terapia de Reposição Hormonal , Humanos , Hipofisectomia/métodos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Doenças da Hipófise/etiologia , Hormônios Hipofisários/sangue , Hormônios Hipofisários/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
J Cardiovasc Pharmacol ; 73(2): 105-117, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30540683

RESUMO

Disorders of lipid metabolism and inflammation play an important role in atherosclerosis. LongShengZhi (LSZ) capsule, a Chinese herbal medicine, has been used for treatment of patients with vascular diseases for many years. In this article, we determined the effect of LSZ on the progression of established atherosclerotic lesions in apoE-deficient (apoE) mice. ApoE mice were prefed high-fat diet (HFD) for 8 weeks to induce atherosclerosis, then started with LSZ treatment contained in HFD for 10 weeks. Although LSZ had little effect on HFD-induced hypercholesterolemia, it substantially reduced en face and sinus aortic lesions. The reduction of lesions was associated with reduced macrophage/foam cell accumulation by activating ABCA1/ABCG1 expression. LSZ maintained the integrity of arterial wall by increasing collagen or smooth muscle cell content and inhibiting cell apoptosis. LSZ also attenuated HFD-induced fatty liver by down-regulating expression of lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes. Moreover, LSZ demonstrated potent anti-inflammatory effects. In vivo, LSZ reduced serum TNF-α levels, infiltration of neutrophils, Kupffer cells, and expression of inflammatory cytokines in the liver. In vitro, it inhibited lipopolysaccharide or palmitate-induced expression of inflammatory cytokines in macrophages. Therefore, LSZ reduces atherosclerosis by ameliorating hepatic lipid metabolism and inhibiting inflammation.

8.
Front Pharmacol ; 9: 1288, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483130

RESUMO

Wenxin Keli (WXKL) is a widely used Chinese botanical drug for the treatment of arrhythmia, which is consisted of four herbs and amber. In the present study, we analyzed the chemical composition of WXKL using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to tentatively identify 71 compounds. Through typical separate procession, the total extract of WXKL was divided into fractions for further bioassays. Cardiomyocytes and zebrafish larvae were applied for assessment. In vivo arrhythmia model in Cmlc2-GFP transgenic zebrafish was induced by terfenadine, which exhibited obvious reduction of heart rate and occurrence of atrioventricular block. Dynamic beating of heart was recorded by fluorescent microscope and sensitive camera to automatically recognize the rhythm of heartbeat in zebrafish larvae. By integrating the chemical information of WXKL and corresponding bioactivities of these fractions, activity index (AI) of each identified compound was calculated to screen potential active compounds. The results showed that dozens of compounds including ginsenoside Rg1, ginsenoside Re, notoginsenoside R1, lobetyolin, and lobetyolinin were contributed to cardioprotective effects of WXKL. The anti-arrhythmic activities of five compounds were further validated in larvae model and mature zebrafish by measuring electrocardiogram (ECG). Our findings provide a successful example for rapid discovery of bioactive compounds from traditional Chinese medicine (TCM) by activity index based approach coupled with in vivo zebrafish model.

9.
Biomed Pharmacother ; 105: 697-706, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29906748

RESUMO

The malignant phenotype of the cells resulting from human liver cancer is driven by liver cancer stem-like cells (LCSLCs). Transient Receptor Potential Vanilloid-type 2 channel (TRPV2) contributes to the progression of different tumor types, including liver cancer. In the current study, the TRPV2 expression levels give rise to the effect on stemness in liver cancer cell lines. TRPV2 knockdown in HepG2 cells enhanced spheroid and colony formation, and expression levels of CD133, CD44 and ALDH1 whereas the opposite effects were observed in TRPV2 enforced expression in SMMC-7721 cells. Furthermore, TRPV2 overexpression restored inhibition of spheroid and colony formation, and stem cell markers expression in HepG2 cells with TRPV2 silencing. The addition of the TRPV2 agonist probenecid and the TRPV2 antagonist tranilast suppressed and/or increased in vitro spheroid and colony formation, and stem cell marker expression of LCSLCs and/or liver cancer cell lines, respectively. Notably, probenecid and tranilast significantly inhibited or promoted tumor growth of HepG2 xenografts in the severe combined immunodeficiency (SCID) mouse model, respectively. TRPV2 expression at protein levels revealed converse correlation with those of CD133 and CD44 in human hepatocellular carcinoma (HCC) tissue. Collectively, the data demonstrate that TRPV2 exert effects on stemness of liver cancer and is a potential target in the treatment of human liver cancer patients.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Células-Tronco Neoplásicas/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/patologia , Camundongos SCID , Células-Tronco Neoplásicas/patologia , Canais de Cátion TRPV/antagonistas & inibidores , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Cardiovasc Pharmacol ; 72(1): 49-59, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29738376

RESUMO

Formation of thrombosis is mainly associated with dysfunctions of endothelial cells. NaoXinTong capsule (NXT), a traditional Chinese medicine, has been demonstrated multiple protective effects on vascular systems. However, it is unknown the effect of NXT on thrombosis. In this study, we determined whether NXT can inhibit carrageenan-induced thrombosis and the underlying mechanisms. Two days after carrageenan injection, severe thrombi were found in blood vessels of mouse tail and liver. By contrast, thrombi were substantially reduced by NXT treatment, and the reduction was associated with reduced serum tumor necrosis factor α and P-selectin levels. In vitro, NXT reduced lipopolysaccharide-activated adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) by inhibiting expression of adhesion molecules and interleukin 6, and reducing production of mitochondrial superoxide that is related to activation of antioxidant enzymes expression. NXT also reduced oxidized low-density lipoprotein-activated adhesion of platelets to HUVECs. In addition, NXT protected HUVECs against clopidogrel-induced cell death by inhibiting expression of tumor necrosis factor-like cytokine 1A and activating expression of vascular endothelial growth factor α. Taken together, our study indicates the potential application of NXT in antithrombosis by multiple antithrombotic functions.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Carragenina , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Fibrinolíticos/farmacologia , Fígado/irrigação sanguínea , Cauda/irrigação sanguínea , Trombose/prevenção & controle , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cápsulas , Adesão Celular/efeitos dos fármacos , Clopidogrel/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Fibrinolíticos/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Pós , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Trombose/sangue , Trombose/induzido quimicamente , Trombose/patologia
11.
Biomed Pharmacother ; 101: 910-919, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29635900

RESUMO

TRPV4 (transient receptor potential vanilloid 4), a member of the TRP superfamily, has been reported to correlate with several different forms of cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC) remains unclear. The present study demonstrated that elevated expression of TRPV4 was shown in HCC tumor tissues when compared with paired non-tumoral livers both in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was highly associated with histological grade (P = 0.036) and the number of tumors (P = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis and decreased the migration capability by attenuating the epithelial-mesenchymal transition (EMT) process in vitro. The p-ERK expression was apparently repressed after treatment with the TRPV4 antagonist, further blockade of the ERK pathway with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse xenograft models, intraperitoneal injection of HC-067047 could obviously suppress tumor growth and induce apoptosis in vivo. Together, our studies showed that the antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be attributed to the suppression of EMT process and inactivation of p-ERK which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 channel may be an option for HCC treatment.


Assuntos
Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , Canais de Cátion TRPV/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade
12.
Exp Ther Med ; 15(3): 2643-2648, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29456667

RESUMO

The aim of the present study was to investigate the mechanism of action by which naringin reverses the resistance of ovarian cancer cells to cisplatin. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting assays were used to detect the effects of different concentrations of naringin on the expressions of nuclear factor (NF)-κB and P-glycoprotein (P-gp) in the SKOV3/CDDP cell line. Small interfering RNA (siRNA) targeting NF-κB was designed and synthesized to silence NF-κB, and recombinant plasmid vectors overexpressing NF-κB were constructed to transfect cells. RT-qPCR and western blotting assays were subsequently performed to detect the effects of NF-κB on the expression of P-gp at the mRNA and protein levels. Naringin was added to the NF-κB-overexpressing SKOV3/CDDP cells and cultured for 48 h, followed by the detection of the expression of P-gp. RT-PCR and western blotting results demonstrated that the gene and protein expressions of NF-κB and P-gp were significantly decreased in a dose-dependent manner by naringin treatment (P<0.05). In cells overexpressing NF-κB, P-gp expression was significantly elevated (P<0.05), and the expression of P-gp was significantly decreased when NF-κB was silenced (P<0.05). Treatment with naringin was able to significantly ameliorate the NF-κB-induced overexpression of P-gp (P<0.05). These results indicate that naringin is able to inhibit the expression of NF-κB and P-gp in SKOV3/CDDP cells. Such an inhibitory effect may increase gradually with concentration, and is associated with blockade of the NF-κB signaling pathway. This pathway may represent one of the mechanisms of action by which Naringin reverses resistance to platinum-based agents in ovarian cancer cells.

13.
Life Sci ; 192: 91-98, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29166570

RESUMO

AIMS: Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown. MAIN METHODS: We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points. KEY FINDINGS: Compared with the PHx group mice, splenectomy accelerated hepatocyte proliferation in PHs group. The expression of Zonula occludens-1 (ZO-1) indicated that splenectomy promotes the formation of tight junction during liver regeneration. TNF-α, IL-6, HGF, TSP-1 and TGF-ß1 were essential factors for the formation of tight junction and the establishment of hepatocytes polarity in liver regeneration. After splenectomy, Partitioning defective 3 homolog (Par 3) and atypical protein kinase C (aPKC) regulate hepatocyte localization and junctional structures in regeneration liver. SIGNIFICANCE: Our data suggest that the time course expression of TNF-α, IL-6, HGF, TSP-1, and TGF-ß1 and the change of platelets take part in liver regeneration. Combination with splenectomy accelerates liver regeneration by improvement of the tight junction formation which may help to establish hepatocyte polarity via Par 3-aPKC. This may provide a clue for us that splenectomy could accelerate liver regeneration after partial hepatectomy of hepatocellular carcinoma and living donor liver transplantation.


Assuntos
Hepatectomia , Regeneração Hepática/fisiologia , Proteína Quinase C/fisiologia , Esplenectomia , Junções Íntimas/fisiologia , Animais , Proliferação de Células , Sobrevivência Celular , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Proteína Quinase C/genética , Proteínas de Junções Íntimas/biossíntese , Proteínas de Junções Íntimas/genética , Junções Íntimas/ultraestrutura , Proteína da Zônula de Oclusão-1/biossíntese
14.
Am J Transl Res ; 10(11): 3733-3741, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662623

RESUMO

The essential ingredient of Centella asiatic is asiatic acid (AA). There are a lot of biological activities in AA, such as anti-oxidant, anti-diabetic. However, so far, there have been no reports on the underlying protective mechanism of AA on podocytes. In this research, we observed the morphological changes of podocytes in diabetic rats by optics microscope and transmission electron microscopy and the protective effect of AA. Additionally, we investigated the expressions of nephrin, desmin and p-JNK, JNK in podocytes of diabetic rats and the influence of AA on podocytes and JNK signaling pathway. The results showed that AA could reduce renal function and urinary albumin. It could attenuate abnormal pathological findings of podocytes in kidney tissue of diabetic rats. Besides, treatment with AA could significantly improve the expression of nephrin and decrease expression of desmin. The ratio of p-JNK protein to JNK protein in podocytes was reduced considerably by AA. With the treatment dose of AA increased, the renal protective effect of AA was gradually improved. These results indicate that asiatic acid has a significant protective effect on diabetic nephropathy. Potential mechanisms include inhibiting the production of oxidants effectively, protection of podocytes, and suppression of the JNK signaling pathway activation. Therefore, there is an excellent prospect of using AA to treat diabetic nephropathy.

15.
J Exp Bot ; 68(16): 4613-4625, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28981770

RESUMO

Cytoplasmic male sterile (CMS) rice has been widely used for hybrid rice seed production in China. However, CMS rice suffers from undesirable flowering habits including scattered floret opening time (FOT), which causes different FOTs among parental rice plants and greatly reduces hybrid rice seed production. Little is known about the mechanism of scattered FOT in CMS rice. Our results demonstrate that scattered FOT in CMS rice Zhenshan 97A (ZS97A) resulted from the lack of a driving force to open florets, which was directly caused by retarded lodicule expansion. Our results indicate that retarded lodicule expansion in ZS97A was caused by reduced water accumulation due to retarded accumulation of osmotic regulation substances (ORSs). Further, the retardation in accumulation of ORSs and water were caused by jasmonic acid (JA) deficiency, resulting from down-regulation of OsAOC expression. Applying JA restored scattered FOT in ZS97A by promoting ORS and water accumulation, and inducing the expansion of the lodicules. Taken together, JA deficiency inhibited lodicule expansion by retarding the accumulation of ORSs and water, leading to scattered FOT in CMS rice ZS97A.


Assuntos
Ciclopentanos/metabolismo , Flores/fisiologia , Oryza/metabolismo , Oxilipinas/metabolismo , Quimera , Ciclopentanos/farmacologia , Flores/genética , Regulação da Expressão Gênica de Plantas , Oryza/efeitos dos fármacos , Oryza/fisiologia , Oxilipinas/farmacologia , Infertilidade das Plantas , Água/metabolismo
16.
Biomed Pharmacother ; 94: 140-149, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28759751

RESUMO

Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated guanosine triphosphatase, an important molecule modulating a large number of cells and involved in the regulation of reactive oxygen species (ROS). For the study described here, we supposed that Rac2 knockout protects mice against CCl4-induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced liver tissues. CCl4-treated Rac2 knockout (Rac2-/-) mice had reduced CD24 levels and steatosis. In addition, CCl4-induced high expression of pro-inflammatory cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2 and TGF-ß1 were also down-regulated in Rac2 knockout mice induced by CCl4. Significantly, oxidative stress induced by CCl4 was also suppressed owing to the lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by CCl4, which was reversed in the liver of Rac2-/- mice through western blot and immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to hepatocytes isolated from WT mice and Rac2-/- mice. The data further confirmed the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine, as well as fibrosis-related signals. Of note, production of ROS induced by LPS was reduced in Rac2-/- cells, accompanied with enhanced SOD1, SOD2 and reduced XO and phosphorylated-JNK expressions. Our results indicated that Rac2 played an essential role in acute liver injury induced by CCl4, providing the compelling information of the effects of Rac2 on liver injury, and revealing a novel regulatory mechanism for acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Inflamação/sangue , Estresse Oxidativo , Proteínas rac de Ligação ao GTP/deficiência , Animais , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/complicações , Quimiocinas/sangue , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Técnicas de Inativação de Genes , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/patologia , Masculino , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
17.
Int J Chron Obstruct Pulmon Dis ; 12: 1933-1946, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28740374

RESUMO

The study aimed to determine the relationship between throat microbiome and COPD. Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included. Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity. Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD. The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different. The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria. The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella. Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified. Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD. By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD. Otu4 also showed a slight potential as a COPD biomarker. To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract. This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD.


Assuntos
Bactérias/classificação , Microbiota , Faringe/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Fumar/efeitos adversos , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , China , Estudos Transversais , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ribotipagem , Índice de Gravidade de Doença
18.
Oncotarget ; 8(17): 29101-29115, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28418858

RESUMO

Among the diverse co-regulatory relationships between transcription factors (TFs) and microRNAs (miRNAs), feedback loops have received the most extensive research attention. The co-regulation of TFs and miRNAs plays an important role in colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two isoforms of p63, TAp63 and ΔNp63, via iASPP, while p63 modulates signal transducers and activators of transcription 1 (STAT1) expression by targeting miR-155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124. Taken together, these results reveal a feedback loop between miRNAs and TFs. This feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and ΔNp63, which are essential for CRC growth. Moreover, this feedback loop is perturbed in human colon carcinomas, which suggests that the manipulation of this microRNA-TF feedback loop has therapeutic potential for CRC.


Assuntos
Neoplasias Colorretais/genética , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Imunoprecipitação da Cromatina , Neoplasias Colorretais/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Int J Biol Markers ; 32(2): e182-e189, 2017 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-28315505

RESUMO

BACKGROUND: A number of studies have been conducted to explore the relationship between CD24 expression and the prognosis of breast cancer; however, the results remain inconsistent. Therefore, we performed this meta-analysis to clarify the impact of CD24 expression on clinicopathological features and prognosis of breast cancer. METHODS: A comprehensive literature search for relevant studies was performed, and statistical analysis was conducted using Stata software. RESULTS: Twenty studies, including 5,179 cases, were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (odds ratio [OR] = 0.68, for negative vs. positive, 95% confidence interval [95% CI], 0.53-0.87, p = 0.002) and TNM stage (OR = 0.63, for I + II vs. III + IV, 95% CI, 0.49-0.81, p<0.001). The prognosis analysis also suggested CD24 overexpression indicated a poorer 5-year overall survival (OS) rate (relative risk ratio [RR] = 0.93, 95% CI, 0.86-0.99, p = 0.03) and 5-year disease-free survival (DFS) rate (RR = 0.90, 95% CI, 0.83-0.98, p = 0.02). However, CD24 expression had no correlation with tumor size, tumor grade, distance metastasis, estrogen receptor (ER) status, progesterone receptor (PR) status, or HER2 status. CONCLUSIONS: Our results suggest that higher CD24 expression is significantly associated with lower OS rate, lower DFS rate and some clinicopathological factors such as lymph node invasion and TNM stage. This meta-analysis suggested that CD24 is an efficient prognostic factor in breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Antígeno CD24/genética , Prognóstico , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Invasividade Neoplásica/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Receptores de Progesterona/genética
20.
Future Oncol ; 13(11): 1021-1034, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28088868

RESUMO

AIM: To assess the prognostic values of Ki-67 in neoadjuvant setting for breast cancer patients. METHODS: PubMed and EMBASE were searched. Revman software was used to conduct random-effect model meta-analysis. RESULTS: 49 studies (14,076 patients) were included. High Ki-67 before and after neoadjuvant chemotherapy were associated with worse overall survival (OS; before: hazard ratio [HR]: 2.29; 95% CI: 1.42-3.69; after: HR: 2.24; 95% CI: 1.82-2.75) and disease-free survival (DFS; before: HR: 1.54; 95% CI: 1.23-1.95; after: HR: 2.08; 95% CI: 1.83-2.37). Low/no reduction or increase might be associated with worse DFS (HR: 2.13; 95% CI: 1.51-3.02) and OS. CONCLUSION: Ki-67 before and after neoadjuvant chemotherapy, as well as the change could predict the prognosis for breast cancer patients.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Antígeno Ki-67/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Terapia Neoadjuvante , Prognóstico , Viés de Publicação , Análise de Sobrevida , Resultado do Tratamento
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