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1.
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 , Revisão Sistemática como Assunto
2.
J Vasc Surg ; 2019 Jul 18.
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.

3.
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.

4.
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.

5.
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.

6.
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
7.
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
8.
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 , 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 , Proteínas Quinases/imunologia , Células THP-1 , Ubiquitina-Proteína Ligases/imunologia
9.
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
10.
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
11.
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
12.
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.

13.
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
14.
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
15.
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
16.
J Neurol Surg A Cent Eur Neurosurg ; 79(1): 9-14, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28743135

RESUMO

BACKGROUND: The treatment of paraclinoid aneurysms can be challenging due to their relationship to the cavernous sinus, carotid siphon, and optic nerve. The goal of this retrospective analysis is to compare the efficacy and safety of microsurgical versus endovascular treatments for ruptured paraclinoid aneurysms. METHODS: Medical records were reviewed to collect information about patient demographics, risk factors, diagnosis (the position and size of aneurysms), Hunt and Hess grade, and surgical method and outcomes, including modified Rankin Scale (mRS) at the time of discharge and 6 months later, complications, and death. RESULTS: In total, 15 and 6 patients were recruited into the microsurgery and endovascular groups, respectively. No difference was detected regarding age, sex, risk factors, and Hunt and Hess grade. Most patients had ophthalmic segment aneurysms (87% versus 83%; p = 1.000) and small aneurysms (< 10 mm, 67% versus 100%; p = 0.102). In the microsurgical group, five patients (33%) had large aneurysms (10-25 mm); three patients (20%) had multiple aneurysms (all p > 0.05 compared with the endovascular group). The occlusion rate at 6 months was 93% in the microsurgical group and 100% in the endovascular group (p > 0.05). No difference was found regarding mRS or the complication and mortality rates between the two groups (all p > 0.05). The occurrence of complications was not related to the location and size of aneurysms (all p > 0.05). CONCLUSIONS: Our retrospective analysis indicates that good clinical outcomes can be achieved with both microsurgical and endovascular approaches. But further prospective randomized multicenter studies are needed to provide more evidence for clinical practice.


Assuntos
Aneurisma Roto/cirurgia , Artéria Carótida Interna/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
J Craniofac Surg ; 28(6): 1442-1444, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28863106

RESUMO

The present study aims to explore the effectiveness of decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes, as well as the outcomes of early cranioplasty. The authors performed the bifrontal decompressive craniectomy on 56 patients with contusion and laceration of bilateral frontal and temporal lobes, and their follow-up treatment outcomes were tracked within 6 months using Glasgow Outcome Scale. The results showed that 33 patients (out of 56, 58.9%) have recovered, 12 patients (out of 56, 21.4%) have moderate defects, 5 patients (out of 56, 8.9%) have severe defects, 3 patients (out of 56, 5.3%) stayed in persistent vegetative status, and the remaining 3 patients (out of 56, 5.3%) have been dead. There was no persistent temporal hollowing. No patients required revision surgery with modified titanium mesh in this study. Particularly, 28 patients have successfully accepted the early cranioplasty with bone flap or computer-assisted design titanium mesh, and showed good recovery. These results together indicated that the decompressive craniectomy with bifrontal coronal incision in the management of severe contusion and laceration of bilateral fronto-temporal lobes can significantly relieve the comorbidity of intracranial hypertension, and improve the prognosis obviously, thus finally increasing the probability of successful rescue and decreasing the probability of mortality and disability.


Assuntos
Lesões Encefálicas/cirurgia , Contusões/cirurgia , Craniectomia Descompressiva/métodos , Lacerações/cirurgia , Craniectomia Descompressiva/efeitos adversos , Craniectomia Descompressiva/estatística & dados numéricos , Seguimentos , Escala de Resultado de Glasgow , Humanos , Crânio/cirurgia , Resultado do Tratamento
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(4): 520-525, 2017 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-28752968

RESUMO

OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG /LC3-Ⅱ Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis (AA). METHODS: Rats were divided for four groups: normal control (NC), model control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12 rats in each group.The AA model was established through Freund's complete adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce inflammation and 10 days of tail root injection of 0.05 mL Freund's complete adjuvant for immunity strengthening. Drug administration started 13 days after induction of inflammation. Rats in the NC and MC groups were given normal saline (1 mL/100 g) once a day for 30 days, compared with 5 mg/kg of oral LEF for the rats in the LEF group and 50 µg/kg of oral TP for the rats in the TP group. Paw swelling (E), joint arthritis index(AI) and joint pathological changes of the rats were recorded. The serum expressions of cytokines B lymphocyte stimulating factor (BAFF), interleukin (IL)-1, tumor necrosis factor (TNF) alpha, IL-15,and IL-10 were detected by ELISA. The expressions of Atg5, Atg7, and Atg12 mRNA in synovial, spleen, and thymus of the rats were detected by RT-PCR.The expressions of LC3-Ⅱ and Beclin1 in synovial, spleen, and thymus of the rats were detected by Western blot assay. RESULTS: The AA model rats had lower serum BAFF, IL-1, TNF alpha, IL-15, and IL-10; lower Atg5and Atg12 mRNA in synovial; lower Atg5 mRNA, Atg7, and Atg12 mRNA in spleen; higher Atg12 mRNA in thymus; and lower LC3-Ⅱ and Beclin1 in synovial, spleen and thymus(P<0.05 or 0.01). TP treatment led to reduced paw swelling and arthritis index; declined Atg7 and Atg12 mRNA in synovial; declined Atg5, Atg7 mRNA and Atg12 mRNA in spleen; decreased Atg5 and Atg7mRNA in thymus; increased Atg12 mRNA in thymus; and increased LC3-Ⅱ and Beclin1 in synovial, spleen and thymus (P<0.05 or 0.01). Compared with rats treated with LEF, TP treated rats had lower TNF-α and BAFF and higher E and IL-15 (P<0.05 or 0.01); as well as decreased expressions of Atg7 mRNA (synovial) and Atg5, Atg7 mRNA (thymus), and increased expressions of Atg12 mRNA (thymus) and Atg5, Atg7, Atg12 mRNA (spleen). CONCLUSION: TP regulates autophagy in synovial, thymus and spleen of AA rats, and improves theirjointinflammatory response.


Assuntos
Artrite Experimental/tratamento farmacológico , Autofagia , Diterpenos/farmacologia , Fenantrenos/farmacologia , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Proteína 12 Relacionada à Autofagia/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Fator Ativador de Células B/metabolismo , Proteína Beclina-1/metabolismo , Compostos de Epóxi/farmacologia , Interleucinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos , Membrana Sinovial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Opt Express ; 25(9): 10335-10344, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28468406

RESUMO

We present a theoretical investigation on controlling the transverse shift while most of the researches are on longitudinal Goos-Hänchen shift. A two-layer system is considered. The refractive index of the first layer is fixed. The second layer is an atomic system coupled by a strong laser field to realize the Λ-style electromagnetically induced transparency, and an additional microwave field drives the transition between the lower two levels to construct high refractive index with zero absorption. We use such phenomenon to modify the refractive index, and consequently the transverse shift in reflection. The properties of the atomic system and the transverse shift of reflected field are briefly studied. Our investigation shows that the shift can be tuned by the strength of the microwave field. And since the atomic system is quite sensitive to the phase of the light fields, through which the transverse shift can be manipulated effectively. More importantly, the absorption is limited due to the presence of the microwave field.

20.
Pharmacol Res ; 121: 70-82, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28456683

RESUMO

Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.


Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Sulfato de Dextrana , Sesquiterpenos/uso terapêutico , Triptofano/metabolismo , Animais , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Citocinas/análise , Masculino , Camundongos Endogâmicos BALB C , Pogostemon/química , Sesquiterpenos/química
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