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1.
Trials ; 21(1): 813, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993769

RESUMO

BACKGROUND: Currently, whether and when intraocular pressure (IOP)-lowering medication should be used in glaucoma suspects with high myopia (GSHM) remains unknown. Glaucoma suspects are visual field (VF) defects that cannot be explained by myopic macular changes or other retinal and neurologic conditions. Glaucoma progression is defined by VF deterioration. Here we describe the rationale, design, and methodology of a randomized controlled trial (RCT) designed to evaluate the effects of medically lowering IOP in GSHM (GSHM study). METHODS: The GSHM study is an open-label, single-center, RCT for GSHM. Overall, 264 newly diagnosed participants, aged 35 to 65 years, will be recruited at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between 2020 and 2021. Participants will be randomly divided into two arms at a 1:1 ratio. Participants in the intervention arm will receive IOP-lowering medication, while participants in the control arm will be followed up without treatment for 36 months or until they reach the end point. Only one eye per participant will be eligible for the study. If both eyes are eligible, the eye with the worse VF will be recruited. The primary outcome is the incidence of glaucoma suspect progression by VF testing over 36 months. The secondary outcomes include the incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer, and retinal ganglion cell-inner plexiform layer loss, progression of myopic maculopathy, visual function loss, and change in the quality of life. Statistical analyses will include baseline characteristics comparison between the intervention and control groups using a two-sample t-test and Wilcoxon rank sum test; generalized linear models with Poisson regression for the primary outcome; Kaplan-Meier curve and log-rank test for the incidence of the secondary outcome; and longitudinal analyses to assess trends in outcomes across time. DISCUSSION: To the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM. TRIAL REGISTRATION: ClinicalTrials.gov NCT04296916 . Registered on 4 March 2020.

2.
Nat Prod Res ; : 1-8, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32608259

RESUMO

Three new benzofuran derivatives, namely ribisin E (1) ribisin F (2) along with ribisin G (3) were isolated from the MeOH extract of the fruiting bodies of Phellinus ribis. Their structures were elucidated based on the NMR analysis. Furthermore, the absolute configuration of ribisin E (1) and ribisin G (3) were deduced by the CD calculations, and the absolute configuration of ribisin F (2) was determined by comparing its CD spectrum and specific rotation with the data of known analogues. All compounds (1-3) exhibited the activity of promoting neurite outgrowth in nerve growth factor (NGF)-ediated PC 12 cell at concentrations ranging from 1 to 30 µM.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 881-885, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552952

RESUMO

OBJECTIVE: To study the correlation of the expression alteration of Tim-3 with the T cell and B cell dysfunction in peripheral blood of multiple myeloma (MM) patients. METHODS: 30 patients diagnosed as MM from October 2016 to October 2018 were selected and enrolled in MM group, and 30 healthy persons whose sex and age was matched with the MM patients were selected and enrolled in healthy control group (HC). The blood samples from MM patients and HC were collected, and the peripheral blood mononuclear cells (PBMNC) were separated by density gradient centrifugation, then the serum was kept for further study. The ratios of CD3+CD4+Tim-3+T cells, CD3+CD8+Tim-3+T cells and the CD19+CD20-CD38+B cells were analysed by flow cytometry (FCM),and the concentration of T cell-related cytokines IFN-γ, TNF-αand B cell-related antibodies IgA, IgM and IgG were measured by ELISA. At the same time, the differences of the ratios of CCD3+CD4+Tim-3+T, CD3+CD8+Tim-3+T cells and plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG between the MM patient and HC were estimated, and the correlation of the ratio of CD3+CD4+Tim-3+T, CD3+CD8+Tim-3+T cells with the ratio of plasmablast and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG in MM patients were analyzed. RESULTS: The ratio of CD3+CD4+Tim-3+T, CD3+CD8+Tim-3+T cells increased in MM patients, while the ratio of CD19+CD20- CD38+B cells and the concentration of IFN-γ, TNF-α, IgA, IgM and IgG decreased in MM patients. And there was a negative correlation of the ratio of CD3+CD4+Tim-3+T cells with CD19+CD20-CD38+B cells and the concentration of IFN-γ, IgA, IgM and IgG in MM patients, while the ratio of CD3+CD8+Tim-3+T cells just negatively correlated with the concentration of TNF-α. CONCLUSION: Expression of Tim-3 on CD4 and CD8 cells elevates in the peripheral blood of MM patients, which also correlates with the function suppression of T and B cells.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Mieloma Múltiplo , Linfócitos B , Linfócitos T CD8-Positivos , Humanos , Leucócitos Mononucleares
4.
Infect Dis Poverty ; 9(1): 52, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414419

RESUMO

BACKGROUND: With the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier. MAIN TEXT: The China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials. A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network. CONCLUSIONS: The CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China's TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.


Assuntos
Fortalecimento Institucional , Ensaios Clínicos como Assunto/métodos , Saúde Global , Cooperação Internacional , Tuberculose/terapia , China
5.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1090-1096, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237451

RESUMO

There were significant differences in phenolic acid content between fresh and dried Salvia miltiorrhiza before and after drying. That is to say, the content of phenolic acid in S. miltiorrhiza significantly increased with the increase of dehydration during the drying process.In order to investigate the differences and transformation of free and bound phenolic acids before and after the drying process of S.miltiorrhiza, we studied hydrolysis method, hydrolysates and hydrolysis regularity of phenolic acids in S.miltiorrhiza. UPLC method was used to determine four main hydrolysates of bound phenolic acids, namely danshensu, caffeic acid dimer(SMND-309), caffeic acid, przewalskinic acid A(prolithosperic acid), and three main free phenolic acids in S.miltiorrhiza, namely rosmarinic acid, lithospermic acid, salvianolic acid B. The results of the acid-base hydrolysis experiment of salvianolic acid showed that the alkaline hydrolysis effect was significantly better than acid hydrolysis. The optimal alkaline hydrolysis condition was hydrolysis at 70 ℃ for 4 h with 2 mol·L~(-1) NaOH solution containing 1% ascorbic acid(Vit C). The hydrolysates of free phenolic acids were the same with the hydrolysates of bound phenolic acids. Fresh S.miltiorrhiza contains a low level of free phenolic acids and a high level of bound phenolic acids, which were exactly opposite to dried S.miltiorrhiza. It was suggested that a large amount of bound phenolic acids was accumulated during the growth of S.miltiorrhiza. These bound phenolic acids were coupled with polysaccharides on the cytoderm through ester bonds to form insoluble phenolic acids, which was not easy to be detected by conventional methods. However, during drying and dehydration processes, the bound phenolic acids were converted to a large amount of free phenolic acids under the action of the relevant enzyme.


Assuntos
Dessecação , Hidroxibenzoatos/análise , Salvia miltiorrhiza/química
6.
Diabetologia ; 63(4): 811-824, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32008054

RESUMO

AIMS/HYPOTHESIS: Although obesity is a predisposing factor for pancreatic beta cell dysfunction, the mechanisms underlying its negative effect on insulin-secreting cells is still poorly understood. The aim of this study was to identify islet long non-coding RNAs (lncRNAs) involved in obesity-mediated beta cell dysfunction. METHODS: RNA sequencing was performed to analyse the islets of high-fat diet (HFD)-fed mice and those of normal chow-fed mice (NCD). The function in beta cells of the selected lncRNA 1810019D21Rik (referred to in this paper as ROIT [regulator of insulin transcription]) was assessed after its overexpression or knockdown in MIN6 cells and primary islet cells, as well as in siRNA-treated mice. Then, RNA pull-down, RNA immunoprecipitation, coimmunoprecipitation and bisulphite sequencing were performed to investigate the mechanism of ROIT regulation of islet function. RESULTS: ROIT was dramatically downregulated in the islets of the obese mice, as well as in the sera of obese donors with type 2 diabetes, and was suppressed by HNF1B. Overexpression of ROIT in MIN6 cells and islets led to improved glucose homeostasis and insulin transcription. Investigation of the mechanism involved showed that ROIT bound to DNA methyltransferase 3a and caused its degradation through the ubiquitin proteasome pathway, which blocked the methylation of the Nkx6.1 promoter. CONCLUSIONS/INTERPRETATION: These findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment. DATA AVAILABILITY: The raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991).

7.
J Ethnopharmacol ; 251: 112554, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31923541

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is tightly associated with inflammation response and oxidative stress. As a folk medicine applied in treatment of diarrhea, Bruguiera gymnorrhiza also possesses anti-inflammatory and anti-oxidative activities, which indicated that B. gymnorrhiza may exert anti-colitis effect. AIM OF THE STUDY: To investigate effect and mechanism of B. gymnorrhiza on experimental UC. MATERIALS AND METHODS: Aqueous extract of B. gymnorrhiza leaves (ABL) was used for investigation in the present study. Murine UC was established through access to 3% dextran sulfate sodium (DSS) for 7 days. Meanwhile, mice accepted treatment with ABL (25, 50, 100 mg/kg) or sulfasalazine (200 mg/kg) once daily. On the last day, disease activity index (DAI) including body weight loss, fecal character and degree of bloody diarrhea was evaluated, colon segments were obtained for length measurement and further analysis and feces were collected for intestinal microbiota analysis. RESULTS: ABL ameliorated DAI scores, colon length shortening and histopathological damage in DSS-induced colitis mice obviously. SOD activity, levels of MDA and GSH altered by colitis were restored remarkably after ABL treatment. ABL inhibited increases in levels of colonic COX-2, iNOS, TNF-α, IL-6, IL-1ß, IL-4, IL-10 and IL-11 in colitis mice. Moreover, ABL prominently suppressed NF-κB p65 and IκB phosphorylation and down-regulated mRNA levels of COX-2, iNOS, TNF-α, IL-6 and IL-1ß elevated by colitis. As shown in microbiota analysis, ABL modulated composition of intestinal microbiota of colitis mice. CONCLUSION: ABL exhibited protective effect against DSS-induced ulcerative colitis through suppressing NF-κB activation and modulating intestinal microbiota.

8.
Planta Med ; 86(4): 255-266, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31975362

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Lipogênese , Fígado , Pogostemon , Ratos
9.
Biotechnol J ; 15(2): e1900135, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31464064

RESUMO

Microalgae have long been considered as potential biological feedstock for the production of wide array of bioproducts, such as biofuel feedstock because of their lipid accumulating capability. However, lipid productivity of microalgae is still far below commercial viability. Here, a glucose-6-phosphate dehydrogenase from the oleaginous microalga Nannochloropsis oceanica is identified and heterologously expressed in the green microalga Chlorella pyrenoidosa to characterize its function in the pentose phosphate pathway. It is found that the G6PD enzyme activity toward NADPH production is increased by 2.19-fold in engineered microalgal strains. Lipidomic analysis reveals up to 3.09-fold increase of neutral lipid content in the engineered strains, and lipid yield is gradually increased throughout the cultivation phase and saturated at the stationary phase. Moreover, cellular physiological characteristics including photosynthesis and growth rate are not impaired. Collectively, these results reveal the pivotal role of glucose-6-phosphate dehydrogenase from N. oceanica in NADPH supply, demonstrating that provision of reducing power is crucial for microalgal lipogenesis and can be a potential target for metabolic engineering.

10.
Int J Mol Med ; 45(2): 343-352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789424

RESUMO

Oxidative and inflammatory damage has been suggested to play important roles in the pathogenesis of skin photoaging. Andrographolide sodium bisulfate (ASB) is a soluble derivative of andrographolide and has known antioxidant and anti­inflammatory properties. In the present study, cellular experiments were designed to investigate the molecular mechanisms underlying the effect of ASB in relieving ultraviolet (UV)­induced photo­damage. Following ASB pretreatment and UV irradiation, the apoptosis and necrosis of HaCaT cells were investigated by Hoechst 33342/propidium iodide staining. Reactive oxygen species (ROS) production was investigated using a DCFH­DA fluorescence probe. Furthermore, the protein expression levels of p65, NF­κB inhibitor­α, nuclear factor E2­related factor 2 (Nrf2) and kelch­like ECH­associated protein 1 (keap1) were measured via western blotting and immunofluorescence analyses. Furthermore, NF­κB­mediated cytokines were assessed by ELISA, and Nrf2­mediated genes were detected by reverse transcription­quantitative PCR. Pretreatment with ASB markedly increased cell viability, decreased cell apoptosis and decreased UV­induced excess ROS levels. In addition, ASB activated the production of Nrf2 and increased the mRNA expression levels of glutamate­cysteine ligase catalytic subunit and NAD(P)H quinone oxidoreductase 1, while ASB downregulated the protein expression of p65 and decreased the production of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α. These results suggested that ASB attenuates UV­induced photo­damage by activating the keap1/Nrf2 pathway and downregulating the NF­κB pathway in HaCaT keratinocytes.

11.
Huan Jing Ke Xue ; 40(9): 4098-4104, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854873

RESUMO

Adsorption is an economical and effective method for recovering phosphate from wastewater. In order to improve the adsorption capacity of Fe3O4 for phosphate and for easy separation from water under the action of an external magnetic field, CaO2 was used in this study as an oxidant to partially oxidize Fe2+. A phosphorus recovery adsorbent, Ca doped Fe3O4 (CMIO), was prepared and was characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF) and vibrating sample magnetometer (VSM) techniques. The results showed that CMIO had a Ca2+ doped Fe3O4 crystal structure with a saturation magnetization of 38.82 emu·g-1, which was easily separated from water by using an external magnetic field. The phosphorus adsorption capacity of the CMIO decreased with an increase of pH value. When pH=2 and T=25℃, the maximum adsorption capacity was 24.10 mg·g-1, which is almost five times the adsorption capacity of pure Fe3O4. The phosphorus adsorption of CMIO was in accord with the Langmuir isotherm adsorption model, and the adsorption process followed the pseudo-second order kinetic model. The complexation of phosphate occurred on the inner surface of the CMIO to form a ≡Fe-Ca-P ternary complex, which can adsorb phosphorus. Compared with other anions in the aqueous solution, CMIO had good adsorption selectivity to PO43-, and the adsorbed PO43- could be desorbed by NaOH solution.The quality loss of the CMIO was less than 4% once, and multiple recycling was possible.

12.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4634-4640, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872658

RESUMO

There is no consensus on the drying methods of Salvia miltiorrhiza in ancient and modern times,especially on the content of phenolic acid in fresh S. miltiorrhiza. In order to further explore the content of main components in fresh S. miltiorrhiza and study the dynamic changes during the drying process,the content of main components was used as the index in this study to evaluate the processing method,drying method,correlation between dehydration rate and component content for fresh S. miltiorrhiza. In addition,the sealed and unsealed parallel control groups were set to carry out verification test during the drying process. UPLC method was used for determination of seven main components including rosmarinic acid,lithosperic acid,salvianolic acid B,cryptotanshinone,tanshinoneⅠ,methylene salianolate and tanshinone ⅡAin S. miltiorrhiza. The results showed that the fresh S. miltiorrhiza contained low levels of phenolic acid,and the content of phenolic acid increased significantly with the increase of dehydration rate during drying process,while the change of tanshinone was not obvious. In the comparison of three drying methods,we found that drying at 50 ℃ was better than drying in the sun,and drying in the sun was superior to drying in the shade. So,drying at 50 ℃ was the best drying method. The correlation between dehydration and phenolic acid content of S. miltiorrhiza was analyzed by verification test and SPSS software,which further proved that the dehydration rate was significantly positively correlated with the content of phenolic acid components. This study provides reference for the production processing and drying methods of S. miltiorrhiza medicinal materials,which is of great significance for improving the quality of S. miltiorrhiza.


Assuntos
Salvia miltiorrhiza , Abietanos , Dessecação , Raízes de Plantas
13.
Medicine (Baltimore) ; 98(43): e17607, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651869

RESUMO

BACKGROUND: This study aims to provide the best possible evidence-based information on the efficacy and safety of sifalimumab for treatment of skin injury (SI) caused by systemic lupus erythematosus (SLE). METHODS: In this study, electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Social Care Online, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched comprehensively from inceptions to June 30, 2019 without language restrictions. We will include randomized controlled trials (RCTs) on evaluating the efficacy and safety of sifalimumab for SI caused by SLE. Two investigators will conduct study selection, data extraction, and risk of bias assessment independently. We will use RevMan 5.3 Software to perform statistical analysis. RESULTS: This study will lie in the exhaustive and systematic nature of the literature search and its methods for evaluating quality and analyzing RCTs data. Considering the controversial efficacy of the treatment for sifalimumab, this study is responsible for improving the existing evidence on the efficacy and safety of sifalimumab for SI caused by SLE. CONCLUSION: The results of this study will provide latest evidence for judging whether sifalimumab is an effective intervention for patients with SI caused by SLE or not. STUDY REGISTRATION: CRD42019148225.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Dermatopatias/tratamento farmacológico , Pele/lesões , Anticorpos Monoclonais Humanizados , Humanos , Projetos de Pesquisa , Dermatopatias/etiologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
14.
Sci Rep ; 9(1): 11053, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363115

RESUMO

Genitourinary tuberculosis (GUTB) accounts for up to 40% of extrapulmonary tuberculosis cases. Rapid tests for GUTB are urgently needed because it is often associated with delayed health-care seeking, leading to serious consequences. This study evaluated the performance of the Xpert MTB/RIF assay in the rapid diagnosis of urinary tract tuberculosis (UTB) and rifampicin-resistant tuberculosis with urine specimens. In all, 302 patients were included from four hospitals in China. Suspected UTB patients were tested with Xpert, smear, and MGIT 960 culture. Drug susceptibility testing (DST) was conducted for culture-positive cases. The performance of the assays was evaluated against MGIT 960 culture and a composite reference standard (CRS). Among all participants, 150 (49.7%) had CRS-positive UTB, of whom 36 (24.0%) were culture-confirmed. Against culture, Xpert and smear achieved a sensitivity of 94.4% (95% CI: 81.3-99.3%) and 22.2% (95% CI: 10.1-39.2%), respectively. Against CRS, the sensitivity of Xpert, smear and culture was 41.3% (95% CI: 33.4-49.7%), 7.3% (95% CI: 3.7-12.7%), and 24.0% (95% CI: 17.4-31.6%). Xpert had better performance than smear and culture in detecting UTB from urine samples and could be considered for the diagnosis of UTB. Moreover, Xpert showed better performance than MGIT 960-based DST using urine culture.

15.
Medicine (Baltimore) ; 98(30): e16558, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348279

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a very tricky orthopedic condition. If it can not be treated fairly well, it may greatly affect quality of life in patients with RA, and even can cause disability. Total knee arthroplasty (TKA) has reported to treat patients with RA effectively. However, no study has systematically explored its efficacy and complications for patients with RA. METHODS: Seven databases will be searched from their inceptions to the present without any language restrictions: MEDICINE, EMBASE, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. Two authors will carry out all study selection, data extraction, and risk of bias assessment independently. RESULTS: The primary outcome of joint pain will be measured by any pain scales, such as visual analogue scale. The secondary outcomes will include joint function, quality of life, and postoperative adverse events. The joint function will be measured by The Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, or other relevant scales. The quality of life will be assessed by the 36-Item Short Form Health Survey or any related tools. In addition, postoperative adverse events will also be analyzed. CONCLUSIONS: The findings of this study will summarize the latest existing evidence on the efficacy and safety of TKA for patients with RA. ETHICS AND DISSEMINATION: This study does not need ethical approval, because it will not analyze individual data. The results of this study are expected to be disseminated at peer-reviewed journals. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019133274.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia do Joelho , Artrite Reumatoide/patologia , Feminino , Humanos , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , Medição da Dor , Período Pós-Operatório , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
16.
Bioresour Technol ; 289: 121720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271916

RESUMO

Haematococcus pluvialis is a main biological resource for the antioxidant astaxanthin production, however, potential modulators and molecular mechanisms underpinning astaxanthin accumulation remain largely obscured. We discovered that provision of ethanol (0.4%) significantly triggered the cellular astaxanthin content up to 3.85% on the 4th day of treatment. Amongst, 95% of the accumulated astaxanthin was esterified, particularly enriched with monoesters. Ultrastructural analysis revealed that ethanol altered cell wall structure and physiological properties. Antioxidant analyses revealed that astaxanthin accumulation offset the ethanol induced oxidative stress. Ethanol treatment reduced carbohydrates while increased lipids and jasmonic acid production. Transcriptomic analysis uncovered that ethanol orchestrated the expression of crucial genes involved in carotenogenesis, e.g. PSY, BKT and CRTR-b were significantly upregulated. Moreover, methyl jasmonic acid synthesis was induced and played a major role in regulating the carotenogenic genes. The findings uncovered the novel viewpoint in the intricate transcriptional regulatory mechanisms of astaxanthin biosynthesis.


Assuntos
Clorofíceas/metabolismo , Ciclopentanos/metabolismo , Etanol/farmacologia , Oxilipinas/metabolismo , Clorofíceas/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Xantofilas/biossíntese
17.
Stem Cells Dev ; 28(18): 1236-1252, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311463

RESUMO

Restoring ß-cell mass by the transplantation of pancreatic islets is an effective diabetes treatment, but it is limited by the shortage of donor organs. CD133-expressing pancreatic ductal epithelial cells (PDECs) have the ability to generate insulin-producing cells. The expansion of these cells is dependent on extrinsic niche factors, but few of those signals have been identified. In this study, CD133-expressing PDECs were purified by sorting from adult wild-type C57BL/6 mice and TGFßRIInull/null mice. Furthermore, using immunofluorescence and transplantation assays, we found that the inhibition of the transforming growth factor-ß (TGF-ß) pathway promoted the expansion of CD133-expressing PDECs for many generations and maintained the ability of CD133-expressing PDECs to generate insulin-producing cells. Moreover, western blot, qRT-PCR, and dual luciferase assays using TGF-ß inhibitors were performed to identify the mechanisms by which TGF-ß signaling regulates proliferation and differentiation. The results showed that the inhibition of TGF-ß signaling enhanced Id2 binding to the promoter region of the cell proliferation repressor p16 and promoted the expansion of CD133-expressing PDECs, and the increased Id2 binding to NeuroD1 decreased the transcription of Pax6 to maintain CD133-expressing PDECs in the Pdx1-expression stage. Taken together, the effect of TGF-ß antagonists on CD133-expressing PDECs reveals a novel paradigm of signaling that explains the balance between the expansion and differentiation of pancreatic duct epithelial progenitors.

18.
J Pathol ; 248(1): 103-115, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30666650

RESUMO

Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Here, we searched for CRC metastasis-associated circular RNA in a mouse model of liver metastasis of CRC by using RNA (transcriptome)-sequencing. We identified a novel and conserved circular RNA, circ-NSD2, functioning as a promoter of CRC metastasis. Circ-NSD2 expression was elevated in CRC tissues and was markedly increased in advanced stages or metastatic tumours of CRC patients. Gain-of-function and loss-of-function experiments demonstrated that circ-NSD2 promoted migration and metastasis of CRC in vitro and in vivo. Mechanistically, circ-NSD2 acted as a sponge for the tumour suppressor miR-199b-5p and activated DDR1 (discoidin domain receptor tyrosine kinase 1) and JAG1 (Jagged 1) genes, which synergistically helped with cell-matrix interaction, migration and metastasis of CRC cells. Taken together, our findings highlight a novel oncogenic function of circ-NSD2 and uncover a key mechanism for the circ-NSD2/miR-199b-5p/DDR1/JAG1 axis in CRC metastasis, which may serve as a prognostic factor and therapeutic target for antimetastatic therapy in CRC patients. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Neoplasias Colorretais/genética , Histona-Lisina N-Metiltransferase/genética , Neoplasias Hepáticas Experimentais/secundário , MicroRNAs/genética , Animais , Movimento Celular/fisiologia , Proliferação de Células/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Receptor com Domínio Discoidina 1/genética , Receptor com Domínio Discoidina 1/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Transplante de Neoplasias , RNA Circular/genética , RNA Neoplásico/genética , Transdução de Sinais/genética
19.
Phytomedicine ; 52: 272-283, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599908

RESUMO

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Berberina/análogos & derivados , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
J Ethnopharmacol ; 234: 44-56, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30610932

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.


Assuntos
Chrysanthemum/química , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Envelhecimento/patologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dióxido de Carbono/química , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Flores , Galactose/toxicidade , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Superóxido Dismutase/metabolismo
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