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1.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3228-3232, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726033

RESUMO

To study the effect of Huangqin Qingre Chubi Capsules containing serum on the protein expressions of AMPK and FoxO3 a in peripheral blood mononuclear cells of patients with rheumatoid arthritis(RA), in order to explore the mechanism of anti-oxidation. Peripheral anticoagulant was collected from patients and normal people. Monocytes(PBMC) were isolated through density gradient centrifugation, and the logarithmic phase cells were cultured. Drug containing serum was prepared through intragastric admini-stration to SD rats. The rats were divided into five groups, namely normal group, model group, AMPK blocker group(compound C 10 µmol·L~(-1)), medium-dose HQC+AMPK blocker group, and middle-dose HQC group. The cell inhibition rate was calculated by MTT method. The levels of IL-1ß, IL-4, LPO, MDA, SOD and TAOC were detected by ELISA. The expressions of AMPK, p-AMPK, p-FoxO3 a and FoxO3 a were detected by Western blot. The HQC containing serum had an inhibitory effect on human monocytes in peripheral blood. The best concentration was observed in middle-dose HQC, and the best time was 24 hours. Middle-dose HQC group was better than model group, AMPK blocker group and middle-dose HQC + AMPK blocker group in terms of increase of SOD, p-AMPK, p-FoxO3 a and decrease of LPO. It was better than model group and AMPK blocker group in terms of increase of IL-4, TAOC, AMPK, FoxO3 a and decrease of IL-1ß, MDA. The differences were statistically significant(P<0.05 or P<0.01). The HQC containing serum may increase the levels of TAOC and SOD, decrease the level of MDA and LPO, activate AMPK, directly phosphorylate FOXO3 a, enhance its transcriptional activity, and improve the state of oxidative stress in RA patients.


Assuntos
Artrite Reumatoide , Scutellaria baicalensis , Proteínas Quinases Ativadas por AMP , Animais , Cápsulas , Proteína Forkhead Box O3 , Humanos , Leucócitos Mononucleares , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
2.
Oncogene ; 39(27): 5056-5067, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32518374

RESUMO

Williams syndrome transcription factor (WSTF) is a transcription factor and tyrosine kinase. WSTF overexpression promotes migration and proliferation of various cancers, and Ser158 (WSTFS158) phosphorylation plays an important role in this process. However, the role of the other posttranslational modifications of WSTF is unknown. Here, we report that lysine (K) 426 on WSTF is acetylated by MOF and deacetylated by SIRT1. Mechanistically, male-specific lethal (MSL) 1v1 interaction with WSTF facilitates its interaction with MOF for WSTF acetylation, which in turn promotes WSTFS158 phosphorylation. The kinase and transcriptional regulatory activity of WSTF were enhanced by acetylation. WSTFK426ac levels positively and significantly correlated with tumor size, histological grade, and age. Moreover, we demonstrated that acetylated WSTF promotes cancer cell proliferation, migration, invasion, and tumor formation. In conclusion, we identified the enzymes regulating WSTF K426 acetylation, and demonstrated an acetylation-dependent mechanism that modulates the activities of WSTF and contributes to tumorigenesis. Our findings provide new clues to study WSTF-mediated normal development and disease.


Assuntos
Carcinogênese/patologia , Histona Acetiltransferases/metabolismo , Neoplasias/patologia , Fatores de Transcrição/metabolismo , Acetilação , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação da Expressão Gênica , Células HEK293 , Histona Acetiltransferases/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Transplante de Neoplasias , Fosforilação , Processamento de Proteína Pós-Traducional , Interferência de RNA , RNA Interferente Pequeno/genética , Sirtuína 1/genética , Sirtuína 1/metabolismo , Transplante Heterólogo
3.
Dis Markers ; 2020: 7253531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454907

RESUMO

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, and an unfavorable outcome is usually attributed to advanced stage NPC. Current methods for the early diagnosis of NPC have limitations in clinical practice. The aim of this study was to investigate the diagnostic ability of Septin 9 methylation for NPC. A quantitative methylation-sensitive PCR (qMS-PCR) assay was developed to measure the methylation status and levels of Septin 9 in nasopharyngeal tissues and paired swabs from patients with NPC, chronic nasopharyngitis, and healthy donors. Methylated Septin 9 was detected in 92% (23/25) of NPC tissues and 25% (4/16) of nasopharyngitis controls (p < 0.05). High-frequency hypermethylation with decreased mRNA expression of Septin 9 in NPC was also identified. Further, Septin 9 methylation was identified in 90.5% (19/21) of NPC biopsies and 71.4% (15/21) of paired swabs, indicating a good concordance between the two sample types. In addition, methylated Septin 9 was found in 16 (72.7%) nasal swabs from 22 NPC patients, 2 of 19 (10.5%) nasopharyngitis, but not in any of the healthy controls (p < 0.01). The methylation score in nasal swabs of the NPC group was also significantly higher than that of non-NPC controls (p < 0.001). Moreover, receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.882 of Septin 9 methylation tests to discriminate NPC from non-NPC subjects. Our study demonstrated that frequent methylation of Septin 9 was present in NPC. Its detection in nasopharyngeal swabs may provide a minimally invasive and informative method for identifying early NPC cases.

4.
Physiol Plant ; 170(1): 75-92, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32306425

RESUMO

Green leaf volatiles (GLVs) are released by plants when they encounter biotic stress, but their functions in the response to abiotic stress have not been determined. We have previously shown that exogenous application of (Z)-3-hexeny-1-yl acetate (Z-3-HAC), a kind of GLV, could alleviate salt stress in peanut (Arachis hypogaea L.) seedlings; however, notably little is known concerning the transcription regulation mechanisms of Z-3-HAC. In this study, we comprehensively characterized the transcriptomes and physiological indices of peanut seedlings exposed to Z-3-HAC and/or salt stress. Analysis of transcriptome data showed that 1420 genes were upregulated in the seedlings primed with Z-3-HAC under salt stress compared with the non-primed treatment. Interestingly, these genes were significantly enriched in the photosynthetic and ascorbate metabolism-related categories, as well as several plant hormone metabolism pathways. The physiological data revealed that Z-3-HAC significantly increased the net photosynthetic rate, SPAD value, plant height and shoot biomass compared with the non-primed peanut seedlings under salt stress. A significantly higher ratio of K+ :Na+ , reduced-to-oxidized glutathione (GSH:GSSG), and ascorbate-to-dehydroascorbate (AsA:DHA) were also observed for the plants primed with Z-3-HAC compared with the salt stress control. Meanwhile, Z-3-HAC significantly increased the activity of enzymes in the AsA-GSH cycle. Taken together, these results highlight the importance of Z-3-HAC in protecting peanut seedlings against salt stress by affecting photosynthesis, cellular redox homeostasis, K+ :Na+ homeostasis, and phytohormones.


Assuntos
Arachis , Fotossíntese , Acetatos , Glutationa , Homeostase , Oxirredução , Estresse Salino , Plântula , Estresse Fisiológico
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(2): 207-212, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32220189

RESUMO

Objective: To observe the changes of cardiac function in arthritic rats and the effect of triptolide on it. Methods: Forty rats were divided in random into normal control (NC) group, model control (MC) group, leflunomide (LEF) group and triptolide (TP) group. Except for the normal group, rats in the other three groups were injected with Freund's complete adjuvant to create arthritic inflammation in the right hind paws, and the interventional drug was administered on the 12th day after the inflammation. By treating for 30 d, the cardiac function of rats was detected by left ventricular catheterization. The expressions of superoxide dismutase (SOD), malondialdehyde (MDA), reacitve oxygen species (ROS), total antioxidation (T-AOC), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum were measured by enzyme-linked immunosorbent assay. The expressions of keap-like protein 1 ( Keap1), muscular aponeurotic fibrosarcom ( maf) and nuclear factor-E2 related factor2 ( Nrf2) mRNAs in cardiac tissue were detected by real-time PCR. The expressions of Keap1, maf and Nrf2 proteins in heart tissues were detected by Western blot. Results: Comparing with the normal group, the heart rate (HR), heart index (HI), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) of the model group were significantly increased, whereas the maximum change rate of ventricular pressure rise or decline (±dp/dtmax) was significantly decreased ( P<0.01). SOD, MDA, ROS, T-AOC, and TNF-α were all increased, and IL-10 was significantly decreased ( P<0.01). The mRNA and protein expressions of Keap1, maf and Nrf2 in heart tissues were increased ( P<0.01). Comparing with the model group, HR, HI, LVSP, and LVEDP in the triptolide group were significantly decreased, whereas the ±dp/dtmax was significantly increased ( P<0.01). SOD, MDA, T-AOC, ROS, TNF-α decreased while the IL-10 increased ( P<0.05, P<0.01). The expressions of Keap1, maf and Nrf2 mRNAs and proteins in the heart tissues of the triptolide group were decreased ( P<0.01). Conclusion: Triptolide could improve cardiac function in arthritic rats, and the mechanism may related to its ability of improving the anti-oxidationin cardiomyocytes, reducing oxidative stress damage, and inhibiting abnormal immune inflammatory response.


Assuntos
Artrite/complicações , Diterpenos/farmacologia , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Imunossupressores/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Fenantrenos/farmacologia , Animais , Compostos de Epóxi/farmacologia , Cardiopatias/complicações , Proteína 1 Associada a ECH Semelhante a Kelch , Miócitos Cardíacos/fisiologia , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo/efeitos dos fármacos , Ratos
6.
J Vasc Surg ; 71(1): 141-148, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31327613

RESUMO

OBJECTIVE: The purpose of this study was to examine the efficacy and safety of catheter-directed thrombolysis (CDT) for first-line treatment of popliteal and infrapopliteal acute limb ischemia. METHODS: A total of 28 consecutive patients (30 limbs) who underwent CDT for treatment of popliteal and infrapopliteal acute limb ischemia of thromboembolic origin between March 2012 and December 2017 were enrolled in this study. Per the Society for Vascular Surgery, limbs were classified into three runoff score groups: <5, good; 5 to 10, compromised; and >10, poor. The primary end points were primary patency and limb salvage assessed by Kaplan-Meier survival analysis. Secondary end points were technical success and clinical success. The Society for Vascular Surgery-recommended scale for gauging changes in clinical status was used to assess clinical success. Safety of the procedure was evaluated on the basis of periprocedural complications according to the Society of Interventional Radiology classification system. RESULTS: Technical success was achieved in 25 (83.33%) treated limbs. Improved clinical status (grade +3/+2) was achieved in 93.33% of limbs. Primary patency and limb salvage for the entire cohort were 76.67% and 90% at 6 months and 60.0% and 76.67% at 12 months, respectively. The patency rate at 6 months and 12 months was 91.67% and 83.33% for the good runoff group, 80% and 60% for the compromised runoff group, and 50% and 25% for the poor runoff group, respectively. The patency rate of the good runoff group was significantly higher compared with that of the poor runoff group (P = .004). Major amputation rate and mortality rate were 16.67% and 7.14%, respectively, at 12 months. The reintervention rate was 3.57% at 6 months and 21.42% at 12 months. CONCLUSIONS: CDT is safe and effective for revascularization of smaller vessel acute arterial thromboembolism as a primary therapy. However, more studies with a larger sample are warranted.

7.
Medicine (Baltimore) ; 98(51): e18361, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860994

RESUMO

BACKGROUND: Diabetic mellitus erectile dysfunction (DMED) refers to erectile dysfunction (ED) secondary to diabetes. As people's lifestyle changes and the population ages, the incidence of DMED continues to increase. Many clinical trials have proven that PDE5-inhibitors-vardenafil has a significant effect in the treatment of Diabetic mellitus erectile dysfunction. In this systematic review, we aim to evaluate the effectiveness and safety of PDE5-inhibitors-vardenafil for Diabetic mellitus erectile dysfunction. METHODS: We will search PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to February 2019.We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of Diabetic mellitus erectile dysfunction. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of PDE5-inhibitors-vardenafil for treating Diabetic mellitus erectile dysfunction. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018095185.


Assuntos
Complicações do Diabetes , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Dicloridrato de Vardenafila/uso terapêutico , Humanos , Masculino , Metanálise como Assunto , Revisões Sistemáticas como Assunto
8.
Biochem Biophys Res Commun ; 516(1): 270-277, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31248593

RESUMO

Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays critical roles in attenuating various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Bardoxolone (Bard), a synthetic triterpenoid based on natural product oleanolic acid, is one of the most potent Nrf2 activator. However, if Bard could prevent lipopolysaccharide (LPS)-induced ALI by inducing Nrf2 activation and its down-streaming signals, is still poorly understood. In this study, we attempted to explore the protective effect of Bard on ALI and the underlying molecular mechanisms. The results indicated that Bard significantly attenuated ALI through reducing the lung wet/dry weight ratio and protein concentration, neutrophil infiltration, malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and improving superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, Bard effectively ameliorated histopathological alterations, reactive oxygen species (ROS) production, pro-inflammatory cytokines release, and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX2) and high mobility group box 1 (HMGB1). Moreover, the inhibitory role of Bard in inflammation was also attributed to its suppression of nuclear factor-κB (NF-κB) signaling. Furthermore, the activation of mitogen-activated protein kinases (MAPKs) signaling, including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), induced by LPS was substantially ameliorated by Bard. The beneficial effects of Bard on ALI were confirmed in LPS-incubated cells in vitro. Meanwhile, the in vitro studies also demonstrated that Bard-improved ALI was largely due to its role in inducing Nrf2 signaling through a dose-dependent manner. Importantly, we found that Bard-attenuated histological changes, inflammation, ROS production, NF-κB and MAPKs signaling in Nrf2+/+ mice were significantly abolished in mice with Nrf2 knockout. Therefore, our study for the first time provided evidence that Bard could effectively ameliorate LPS-induced ALI by reducing oxidative stress and inflammation mainly through the activation of Nrf2 signaling.

9.
Int Immunopharmacol ; 72: 437-444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030100

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. METHODS: 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. RESULTS: Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. CONCLUSIONS: Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.


Assuntos
Imunossupressores/uso terapêutico , Neuropilina-1/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Talidomida/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Neuropilina-1/genética , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Talidomida/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
10.
Opt Express ; 27(5): 6370-6376, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876223

RESUMO

The research of Airy beams has attained much attention due to their unique characteristics. Coherent control of Airy beams is important for further light beam manipulation and information processing. In this paper, we experimentally investigate the storage and retrieval of 2D Airy wavepackets in a solid-state medium driven by electromagnetically induced transparency (EIT). The transverse profile of the weak probe pulse is modulated by Airy wavepackets. Under EIT condition, the probe Airy wavepackets are stored into the experimental medium by manipulating the intensity of the control field, and later retrieved by the opposite process. The retrieved Airy wavepackets keep a high similarity compared with those before the storage. Furthermore, the self-healing property of the retrieved Airy wavepackets is investigated. This storage of Airy wavepackets develops the control method of Airy beams, which will be useful in further applications.

11.
Zhongguo Zhen Jiu ; 39(1): 65-71, 2019 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-30672259

RESUMO

OBJECTIVE: To explore the effects of huayu tongluo (resolving stasis, promoting collateral circulation) moxibustion on learning and memory ability and the expressions of brain derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the rats of vascular dementia (VD) in the microenvironment of neurovascular niche. METHODS: Using 2-vessel occlusion (2-VO), the VD rat models were duplicated. The neural stem cells (NSCs) labeled with lentiviral vector-mediated enhanced green fluorescent protein (EGFP) were co-cultured with endothelial progenitor cells (EPCs) to structure the NSCs + EPCs implant. The implant was transplanted into the lateral ventricle of VD rats and the VD rat models with neurovascular niche were established. In No.1 experiment, the successful-modeled rats were divided into 3 groups, i.e. a NSCs + EPCs moxibustion group, a NSCs + EPCs blank group and a model group, 12 rats in each one. No any treatment was provided in the model group and the NSCs + EPCs blank group. The huayu tongluo moxibustion therapy was adopted in the NSCs + EPCs moxibustion group, in which, the suspending moxibustion technique was applied to "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenting" (GV 24), 20 min at each acupoint. The treatment was given once every day and a 14-day treatment was as one course. Totally, 3 courses of treatment were required. At the end of treatment, Morris water maze experiment was adopted to determine the learning and memory ability of the rats in each group. In the No.2 experiment, the model rats were divided into 3 groups, a NSCs + EPCs moxibustion group, a NSCs + EPCs blank group and a model group, 18 rats in each one. In each group, according to the durations of treatment, 3 subgroups were divided and 6 rats in each one. The intervention method was same as the No.1 experiment. Additionally, after corresponding treatment course, using perfusion, the brains were collected in each subgroup and the slices were frozen. BDNF/TrkB expressions were observed in the immunofluorescence test. RESULTS: After treatment, in the NSCs + EPCs moxibustion group, the escape incubation was reduced, the time of the first running-cross platform was shortened and the frequency of running-cross platform increased as compared with the model group and the NSCs + EPCs blank group (P<0.01, P<0.05). The protein expressions were increased in tendency among the 3 courses of treatment in the NSCs + EPCs moxibustion group, indicating the significant differences (all P<0.05), in which, the increase of the protein expressions in the NSCs + EPCs moxibustion group was better than the NSCs + EPCs blank group (P<0.05, P<0.01). CONCLUSION: The huayu tongluo moxibustion therapy is the effective approach to VD in clinical treatment. This therapy up-regulates the BDNF/TrkB protein expressions in the microenvironment of neurovascular niche, co-modulates NSCs-EPCs coupling mechanism, promotes nerve neogenesis and repairs the injured nerve.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Demência Vascular , Moxibustão , Proteínas Tirosina Quinases/metabolismo , Animais , Fator B do Complemento , Demência Vascular/metabolismo , Medicamentos de Ervas Chinesas , Hipocampo , Ratos , Ratos Sprague-Dawley
12.
Mol Immunol ; 105: 76-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496979

RESUMO

Activation of NLRP3 inflammasomes is crucial in the pathological process of Ulcerative colitis (UC), which could be negatively regulated by PINK1/Parkin-driven mitophagy. Palmatine is a herb derived isoquinoline alkaloid with potent anti-inflammatory and anti-bacteria activities. In present study, we evaluated the effect of palmatine on dextran sulfate sodium (DSS)-induced mice colitis and examined whether its effect is exerted by promoting mitophagy-mediated NLRP3 inflammasome inactivation. The result showed that palmatine (40, 100 mg/kg) significantly prevented bodyweight loss and colonic shortening in DSS mice, and reduced the disease activity index and histopathologic score. The levels of MPO, IL-1ß, TNF-α and the number of F4/80+ cells in colon of DSS mice were remarkably decreased by palmatine. Moreover, palmatine suppressed NLRP3 inflammasomes activation, but enhanced the expression of the mitophagy-related proteins involving LC3, PINK1 and Parkin in colonic tissue of DSS mice. These effects was consistent with the in vitro data revealing that palmatine inhibited the activation of NLRP3 inflammasomes, while promoted the expression and mitochondrial recruitment of PINK1 and Parkin in THP-1 cell differentiated macrophages. Furthermore, the effect of palmatine on THP-1 cells was neutralized by a mitophagy inhibitor Cyclosporin A (CsA) and PINK1-siRNA. In parallel, CsA significantly attenuated the therapeutic effect of palmatine in DSS mice, illustrating that the anti-colitis effect of palmatine is closely related to mitophagy. Taken together, the current results demonstrated that palmatine protected mice against DSS-induced colitis by facilitating PINK1/Parkin-driven mitophagy and thus inactivating NLRP3 inflammasomes in macrophage.


Assuntos
Colite , Sulfato de Dextrana/toxicidade , Inflamassomos/imunologia , Mitofagia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Ácido Palmítico/farmacologia , Animais , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colite/prevenção & controle , Ciclosporina/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos BALB C , Mitofagia/imunologia , Proteínas Quinases/imunologia , Células THP-1 , Ubiquitina-Proteína Ligases/imunologia
13.
Oncogene ; 38(7): 980-997, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30185813

RESUMO

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.


Assuntos
Autofagia , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Histonas/genética , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/genética , Fosforilação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
14.
Cell Biochem Funct ; 36(8): 398-407, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30484863

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Histone deacetylase inhibitors (HDACIs) have been demonstrated as an emerging class of anticancer drugs for a range of haematological and solid tumours. However, the effect of HDACIs has not yet been investigated on ESCC cells. In this study, HDACIs were initially considered to have anticancer activity for ESCC, due to the high expression of HDAC genes in ESCC cell lines by analysing expression data of 27 ESCC cell lines from the Broad-Novartis Cancer Cell Line Encyclopedia. Next, we used five ESCC cell lines and one normal immortalized esophageal epithelial cell line to screen three HDACIs, panobinostat (LBH589), vorinostat (SAHA), and trichostatin A (TSA), for the ability to inhibit growth. Here, we report that LBH589 more effectively suppressed cell proliferation of ESCC cell lines, in a dose-dependent manner, than TSA and SAHA, as well as had lower toxicity against the SHEE normal immortalized esophageal epithelial cell line. Further experiments indicated that LBH589 treatment significantly inhibited TP53 (mutated TP53) expression, both at the mRNA and protein level, and simultaneously increased p21 and decreased cyclin D1 expression. Taken together, we propose that LBH589 inhibits ESCC cell proliferation mainly through inducing cell cycle arrest by increasing p21 and decreasing cyclin D1 in a p53-independent manner. SIGNIFICANCE OF THE STUDY: In this study, the antitumor activity of HDACIs LBH589, SAHA, and TSA on ESCC was characterized, with LBH589 displaying the most potent anti-proliferative activity while not harming normal immortalized esophageal epithelial cells. Furthermore, we propose that LBH589 exerts its anti-proliferative effect by inducing cell cycle arrest. The ability to specifically target cancer cells indicates therapeutic potential for use of LBH589 in the treatment of ESCC.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Panobinostat/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Pharmacol Res ; 137: 34-46, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30243842

RESUMO

Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1) and the positive drug Sulfasalazine (SASP, 200 mg kg-1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Animais , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Mucinas/genética , Proteínas de Junções Íntimas/genética
16.
World J Gastroenterol ; 24(22): 2400-2405, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904247

RESUMO

AIM: To ascertain the prognostic role of the T4 and N2 category in stage III pancreatic cancer according to the 8th edition of the American Joint Committee on Cancer (AJCC) classification. METHODS: Patients were collected from the Surveillance Epidemiology and End Results (SEER) database (2004-2013) and were divided into three groups: T(1-3)N2, T4N(0-1), and T4N2. Overall survival (OS) and disease-specific survival (DSS) of patients were evaluated by the Kaplan-Meier method. RESULTS: For the first time, we found a significant difference in OS and DSS between T(1-3)N2/T4N(0-1) and T4N2 but not between T(1-3)N2 and T4N(0-1). A higher grading correlated with a worse prognosis in the T(1-3)N2 and T4N2 groups. CONCLUSION: Patients with stage T4N2 had a worse prognosis than those with stage T(1-3)N2/T4N(0-1) in the 8th edition AJCC staging system for pancreatic cancer. We recommend that stage III should be subclassified into stage IIIA [T(1-3)N2/T4N(0-1)] and stage IIIB (T4N2).


Assuntos
Neoplasias Pancreáticas/patologia , Programa de SEER/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/mortalidade , Prognóstico , Adulto Jovem
17.
Sci Rep ; 8(1): 6834, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717173

RESUMO

We theoretically study the optically tunable gratings based on a L-type atomic medium using coherent population oscillations from the angle of reflection and transmission of the probe field. Adopting a standing-wave driving field, the refractive index of the medium as well as the absorption are periodically modified. Consequently, the Bragg scattering causes the effective reflection. We show that different intensities of the control field lead to three types of reflection profile which actually correspond to different absorption/amplification features of the medium. We present a detailed analyses about the influence of amplification on the reflection profile as well. The coherent population oscillation is robust to the dephasing effect, and such induced gratings could have promising applications in nonlinear optics and all-optical information processing.

18.
Ying Yong Sheng Tai Xue Bao ; 29(3): 850-856, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29722227

RESUMO

Clarifying the carbon emissions in wheat-summer direct-seeding peanut planting (W-P) system could help realize the synergistic effects of high yield and low carbon emissions. Based on whole life cycle method, we constructed a carbon footprint model to calculate the carbon emissions of W-P system. We found that the net income of W-P system was 71.2%-88.3% higher than that of wheat-maize rotation (W-M) system. The carbon emissions per unit area under W-P system was 6977.9-8018.5 kg·hm-2, being 6.2% higher than that of W-M system. The carbon emission of per net income under W-P system was 0.23-0.28 kg CO2-eq·yuan-1, which was 37.4%-44.1% lower than that of W-M system. Combining the net income and carbon emissions of per net income, W-P system could achieve synergistic effects of high yield and low carbon emissions, which would fulfill the targets of agricultural supply-side structural reform with optimizing supply, enhancing quality and efficiency, and increasing income of peasants.


Assuntos
Arachis , Pegada de Carbono , Triticum , Agricultura , China
19.
Spine J ; 18(9): 1637-1644, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29567517

RESUMO

BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is widely used for pedicle screw augmentation in osteoporosis. Until now, there had been no studies of the relationship between screw stability and the distribution and volume of PMMA. PURPOSE: The objective of this study was to analyze the relationship between screw stability and the distribution pattern and injected volume of PMMA. STUDY DESIGN: This is a biomechanical comparison of injectable pedicle screws with different lateral holes augmented with different volumes of PMMA in cadaveric osteoporotic lumbar vertebrae. METHODS: Forty-eight osteoporotic lumbar vertebrae were randomly divided into Groups A, B, and C with different pedicle screws (16 vertebrae in each group), and then each group was randomly divided into Subgroups 0, 1, 2, and 3 with different volumes of PMMA (four vertebra with eight pedicles in each subgroup). A pilot hole was prepared in advance using the same method in all samples. Type A and type B pedicle screws were directly inserted into vertebrae in Groups A and B, respectively, and then different volumes of PMMA (0, 1.0, 1.5, and 2.0 mL) were injected through the screws and into vertebrae in Subgroups 0, 1, 2, and 3. The pilot holes were filled with different volumes of PMMA (0, 1.0, 1.5, and 2.0 mL), and then the screws were inserted in Groups C0, C1, C2, and C3. Screw position and distribution of PMMA were evaluated radiographically, and axial pullout tests were performed to measure maximum axial pullout strength (Fmax). RESULTS: Polymethylmethacrylate surrounded the anterior one-third of screws in the vertebral body in Groups A1, A2, and A3; the middle one-third of screws in the junction area of the vertebral body and the pedicle in Groups B1, B2, and B3; and the full length of screws evenly in both the vertebral body and the pedicle in Groups C1, C2, and C3. There was no malpositioning of screws or leakage of PMMA in any sample. Two-way analysis of variance revealed that two factors-distribution and volume of PMMA-significantly influenced Fmax (p<.05) but that they were not significantly correlated (p=.088). Fmax values in groups using augmentation with PMMA values significantly improved compared with those in groups without PMMA (p<.05). CONCLUSIONS: Polymethylmethacrylate can significantly enhance the stability of different injectable pedicle screws in osteoporotic lumbar vertebrae, and screw stability is significantly correlated with the distribution pattern and the injected volume of PMMA. The closer the PMMA to the pedicle and the greater the quantity of injected PMMA, the greater is the pedicle screw stability. Injection of 2.0 mL of PMMA through screws with four lateral 180° holes or of 1.0 mL of PMMA through screws with six lateral 180° holes increases the stability of pedicle screws.


Assuntos
Vértebras Lombares/cirurgia , Osteoporose/cirurgia , Parafusos Pediculares/efeitos adversos , Falha de Prótese , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Cimentos para Ossos/efeitos adversos , Humanos , Polimetil Metacrilato , Fusão Vertebral/efeitos adversos
20.
PLoS One ; 13(3): e0194069, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29538417

RESUMO

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC.


Assuntos
Berberina/análogos & derivados , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Animais , Berberina/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo
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