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1.
Sleep Med Rev ; 48: 101215, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31630016

RESUMO

Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.

2.
Medicine (Baltimore) ; 98(40): e17132, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577704

RESUMO

BACKGROUND: Evidence-based guidelines are expected to provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. However, the existing practice guidelines(CPGs) vary in quality. This study aimed to evaluate the quality of CPGs of kidney cancer. METHODS: We systematically searched PubMed, Embase, China Biology Medicine disc, and relevant guideline websites from their inception to April, 2018. We identified CGPs that provided recommendations on kidney cancer; 4 independent reviewers assessed the eligible CGPs using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. The consistency of evaluations was calculated using intraclass correlation coefficients (ICC). RESULTS: A total of 13 kidney cancer CGPs were included. The mean scores for each AGREEII domain were as follows: scope and purpose-76.9%; clarity and presentation-76.4%; stakeholder involvement-62.8%; rigor of development-58.7%; editorial independence-53.7%; and applicability-49.4%. Two CPGs were rated as "recommended"; 8 as "recommended with modifications"; and 3 as "not recommended." Seven grading systems were used by kidney cancer CGPs to rate the level of evidence and the strength of recommendation. CONCLUSIONS: Overall, the quality of CPGs of kidney cancer is suboptimal. AGREE II assessment results highlight the need to improve CPG development processes, editorial independence, and applicability in this field. It is necessary to develop a standardized grading system to provide clear information about the level of evidence and the strength of recommendation for future kidney cancer CGPs.


Assuntos
Neoplasias Renais/terapia , Guias de Prática Clínica como Assunto/normas , Humanos
3.
Artigo em Inglês | MEDLINE | ID: mdl-31515848

RESUMO

RATIONALE: A thorough understanding of the content and distribution of active ingredients in pharmaceuticals is essential for drug efficacy and safety. Technological advancements in mass spectrometry imaging present an opportunity for methodological innovation by providing qualification and quantification analysis, as well as spatial information, in the same assay, which has great potential for applications in the rapid analysis and quality control of drugs. METHODS: In this work, matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was employed to directly analyze oxytetracycline tablets in order to map the active constituent distribution within the whole tablet. Quantitative analysis was capable of differentiating tablets containing various doses of the active pharmaceutical ingredient. RESULTS: To establish the methodology, detailed factors that influence matrix spraying and spatial resolution during sample preparation and the data acquisition process were optimized systematically. Quantitative analysis could differentiate the tablets containing various doses of the active compound. The proposed method was successfully applied to analyze real commercial tablets. CONCLUSIONS: The developed method could successfully achieve the spatial location of oxytetracycline in actual tablet samples. These results could contribute to pharmaceutical tracing technology, especially the formulation process of tablets, which is helpful for monitoring the quality of pharmaceutical products and guaranteeing drug security.

4.
Int J Biol Macromol ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31479666

RESUMO

For a more insightful investigation into the specificity of bacterial heparinase I, a series of structurally well-defined heparin oligosaccharides was synthesized using a highly efficient chemoenzymatic strategy. Apart from the primary cleavage site, five glycosidic linkages of oligosaccharides with varying modifications to obtain secondary cleavage sites were degraded by a high concentration of heparinase I. The reactivity of linkages toward heparinase I was not entirely dependent on the 2-O-sulfated iduronic acid being cleaved or the neighboring 6-O-sulfated glucosamine residues, but it was dependent on higher degrees of sulfation of oligosaccharides and indispensable N-substituted glucosamine adjacent to the cleavable linkage. Moreover, the enzyme demonstrated less preferential cleavage toward glycosidic linkages containing glucuronic acid than those containing iduronic acid of the counterpart oligosaccharides. Biolayer interferometry revealed differences in reactivity that are not completely consistent with different affinities of substrates to enzyme. Our study presented accurate information on the cleavage promiscuity of heparinase I that is crucial for heparin depolymerization.

5.
Int J Mol Sci ; 20(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533225

RESUMO

Tillers not only determine plant architecture but also influence crop yield. To explore the miRNA regulatory network restraining tiller development in a dwarf-monoculm wheat mutant (dmc) derived from Guomai 301 (wild type, WT), we employed miRNome and transcriptome integrative analysis, real-time qRT-PCR, histochemistry, and determinations of the key metabolites and photosynthesis parameters. A total of 91 differentially expressed miRNAs (DEMs) were identified between dmc and WT. Among them, 40 key DEMs targeted 45 differentially expressed genes (DEGs) including the key DEGs encode growth-regulating factors (GRF), auxin response factors (ARF), and other proteins involved in the metabolisms of hormones and carbohydrates, etc. Compared with WT, both the chlorophyll contents and the photosynthesis rate were lower in dmc. The contents of glucose, sucrose, fructose, and maltose were lower in dmc. The contents of auxin (IAA) and zeatin (ZA) were significantly lower, but gibberellin (GA) was significantly higher in the tiller tissues of dmc. This research demonstrated that the DEMs regulating hormone and carbohydrate metabolisms were important causes for dmc to not tiller. A primary miRNA-mRNA regulatory model for dmc tillering was established. The lower photosynthesis rate, insufficient energy, and abnormal hormone metabolisms restrict tillering in dmc.

6.
Int J Mol Sci ; 20(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546802

RESUMO

Complete differentiation of the spikes guarantees the final wheat (Triticum aestivum L.) grain yield. A unique wheat mutant that prematurely terminated spike differentiation (ptsd1) was obtained from cultivar Guomai 301 treated with ethyl methane sulfonate (EMS). The molecular mechanism study on ptsd1 showed that the senescence-associated genes (SAGs) were highly expressed, and spike differentiation related homeotic genes were depressed. Cytokinin signal transduction was weakened and ethylene signal transduction was enhanced. The enhanced expression of Ca2+ signal transduction related genes and the accumulation of reactive oxygen species (ROS) caused the upper spikelet cell death. Many genes in the WRKY, NAC and ethylene response factor (ERF) transcription factor (TF) families were highly expressed. Senescence related metabolisms, including macromolecule degradation, nutrient recycling, as well as anthocyanin and lignin biosynthesis, were activated. A conserved tae-miR164 and a novel-miR49 and their target genes were extensively involved in the senescence related biological processes in ptsd1. Overall, the abnormal phytohormone homeostasis, enhanced Ca2+ signaling and activated senescence related metabolisms led to the spikelet primordia absent their typical meristem characteristics, and ultimately resulted in the phenotype of ptsd1.

7.
PLoS One ; 14(9): e0217555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31545806

RESUMO

This study aims to evaluate the quality of clinical practice guidelines(CPGs) for patients with diabetic foot worldwide. A search of guidelines websites, databases and academic institutions websites was performed from January 1st, 2010, until June 30th, 2018. Four assessors independently rated the quality of each CPG using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Twelve CPGs satisfied the inclusion criteria. The median scores for the 6 AGREE II domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence) were 92.5%, 72.5%, 71.5%, 89%, 47%, and 77%, respectively. The overall quality of the CPGs was good since the majority of the CPGs reached an overall guideline quality between 5 and 7 points. Different CPGs had widely varying scores in the same area, ranging from 25 to 94 points.

8.
Medicine (Baltimore) ; 98(31): e16629, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374031

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the quality of guidelines for rehabilitation of post-stroke aphasia using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument and identify consistency of different guidelines. METHODS: A systematic search was undertaken from inception to October 2018. Two reviewers independently screened all titles and abstracts, and assessed eligible guidelines using the AGREE-II. Agreement among reviewers was measured by using intra-class correlation coefficient (ICC). RESULTS: From 5008 records screened, 8 guidelines met the inclusion criteria. The quality of guidelines was heterogeneous. Three guidelines were rated high (6.5) across; the highest rated domain was "scope and purpose' (median score 95.8%); the lowest rated domain was "rigor of development' (median score 67.2%). An overall high degree of agreement among reviewers to each domain was observed (ICC ranged from 0.60 to 0.99). The speech language therapy was recommended in 3 guidelines. Four guidelines described group treatment was beneficial for the continuum of care. However, other therapies for aphasia varied in the level of detail across guidelines. CONCLUSIONS: Our study indicated the quality of guidelines for post-stroke aphasia needed to be improved. Moreover, the treatment recommendations of aphasia existed discrepancy among the included guidelines. Therefore, it is suggested to pay more attention on the rigor of methodology and applicability during the process of the formulation of guideline. Future research should focus on the effectiveness, intensity, and duration of treatment measures.


Assuntos
Afasia/reabilitação , Guias de Prática Clínica como Assunto/normas , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/normas , Humanos
9.
FEBS Lett ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369682

RESUMO

Microtubules are composed of αß-tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 Å crystal structure of tubulin in complex with the indole derivative D64131. We compare the binding modes of D64131, colchicine, and five other indole derivatives to tubulin. These results reveal the interactions between the indole derivatives and tubulin, explain previous results of structure-activity-relationship (SAR) studies and, thus, provide insights into the development of new indole derivatives targeting the colchicine binding site.

10.
Medicine (Baltimore) ; 98(29): e16227, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335673

RESUMO

OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of different computer-aided diagnostic (CAD) systems for thyroid nodules classification. METHODS: A systematic search of the literature was conducted from inception until March, 2019 using the PubMed, EMBASE, Web of science, and Cochrane library. Literature selection and data extraction were conducted by 2 independent reviewers. Numerical values for sensitivity and specificity were obtained from false negative (FN), false positive (FP), true negative (TN), and true positive (TP) rates, presented alongside graphical representations with boxes marking the values and horizontal lines showing the confidence intervals (CIs). Summary receiver operating characteristic (SROC) curves were applied to assess the performance of diagnostic tests. Data were processed using Review Manager 5.3 and Stata 15. The methodological quality of included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019132540.


Assuntos
Diagnóstico por Computador , Nódulo da Glândula Tireoide , Ultrassonografia , Confiabilidade dos Dados , Diagnóstico por Computador/efeitos adversos , Diagnóstico por Computador/métodos , Diagnóstico por Computador/normas , Precisão da Medição Dimensional , Humanos , Nódulo da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Ultrassonografia/normas
11.
Medicine (Baltimore) ; 98(29): e16326, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335680

RESUMO

BACKGROUND: Prostate cancer (PCa) is one of the most common primary malignancies in humans and the second leading cause of cancer-specific mortality among Western males. Computer-aided detection (CAD) systems have been developed for accurate and automated PCa detection and diagnosis, but the diagnostic accuracy of different CAD systems based on magnetic resonance imaging (MRI) for PCa remains controversial. The aim of this study is to systematically review the published evidence to investigate diagnostic accuracy of different CAD systems based on MRI for PCa. METHODS: We will conduct the systematic review and meta-analysis according to the Preferred Reporting Items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Cochrane library, PubMed, EMBASE and Chinese Biomedicine Literature Database will be systematically searched from inception for eligible articles, 2 independent reviewers will select studies on CAD-based MRI diagnosis of PCa and extract the requisite data. The quality of reporting evidence will be assessed using the quality assessment of diagnosis accuracy study (QUADAS-2) tool. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curves will be calculated to estimate the diagnostic accuracy of CAD system. In addition, we will conduct subgroup analyses according to the type of classifier of CAD systems used and the different prostate zoon. RESULTS: This study will conduct a meta-analysis of current evidence to investigate the diagnostic accuracy of CAD systems based on MRI for PCa by calculating sensitivity, specificity, and SROC curves. CONCLUSION: The conclusion of this study will provide evidence to judge whether CAD systems based on MRI have high diagnostic accuracy for PCa. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42019132543.


Assuntos
Diagnóstico por Computador/métodos , Imagem por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Protocolos Clínicos , Humanos , Masculino
12.
Zhongguo Zhen Jiu ; 39(7): 685-8, 2019 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-31286727

RESUMO

OBJECTIVE: To observe the therapeutic effect of acupuncture on blood pressure variability (BPV) in elderly patients with cerebral infarction complicated with essential hypertension. METHODS: Seventy-six elderly patients with cerebral infraction complicated with essential hypertension were randomized into an observation group and a control group, 38 cases in each group. Xingnao Kaiqiao acupuncture and nifedipin were given in the control group. On the basis treatment in the control group, the Huoxue Sanfeng and Tiaohe Ganpi acupuncture was applied at Renying (ST 9), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) and Taichong (LR 3) in the observation group for 30 min. The treatment was given once a day, 5 times a week for 8 weeks. The 24-hour ambulatory blood pressure was monitored in the two groups. The changes of blood pressure and blood pressure variability were observed before and after 8 weeks of treatment, and the occurrence of adverse reactions during the treatment were recorded. RESULTS: The mean systolic blood pressure (SBP), diastolic blood pressure (DBP), daytime SBP, DBP, nighttime SBP and DBP were reduced in the two groups after 8 weeks of treatment (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). After 8 weeks of treatment, the daytime, nighttime, 24 h systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) in the observation group were lower than those before treatment (P<0.05), there was no significant difference between before and after treatment in the control group (P>0.05). CONCLUSION: Huoxue Sanfeng and Tiaohe Ganpi acupuncture method can effectively control the blood pressure and blood pressure variability in the elderly patients with cerebral infraction complicated with essential hypertension.


Assuntos
Terapia por Acupuntura , Infarto Cerebral , Hipertensão , Idoso , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Infarto Cerebral/complicações , Humanos , Hipertensão/complicações
13.
Environ Sci Technol ; 53(16): 9472-9480, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31310123

RESUMO

Little is currently known about the trophic transfer behavior of short-chain chlorinated paraffins (SCCPs) in terrestrial ecosystems. The trophodynamics of SCCPs were investigated in a typical terrestrial food chain (plant-plateau pika-eagle) from the interior of the Tibetan Plateau with an altitude of 4730 m. Pervasive contamination by SCCPs was found in the Tibetan Plateau samples, and the average concentrations of SCCPs in soil, plant, plateau pika, eagle, and gut content of eagle samples were 81.6 ± 31.1, 173 ± 70.3, 258 ± 126, 108 ± 59.6, and 268 ± 93.9 ng/g (average ± standard deviation, dry weight, dw), respectively. The trophic magnification factor (TMF) of SCCPs was 0.37, implying the trophic dilution of SCCPs in this terrestrial food chain. The TMF values of individual congener groups were positively correlated with the values of log Kow, log Koa and biotransformation half-life. As a result of long-range transport, SCCPs congeners with low molecular weight dominated in Tibetan Plateau species (C10+11 congeners = 76.9%, Cl5+6+7 congeners = 71.5%), which could partly explain the low biomagnification factors (BMFs) of SCCPs in the Tibetan Plateau.

14.
Complement Ther Med ; 45: 114-123, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331547

RESUMO

OBJECTIVES: To summarize the evidence from systematic reviews (SRs) and meta-analyses that evaluated the efficacy of ginger in treating any conditions and critically assess the quality of these evidence. METHODS: A systematic search of the literature was conducted from inception until February 28, 2019 using the PubMed, EMBASE, Web of science, Cochrane library, and four Chinese databases. Literature selection and data extraction were conducted by two independent reviewers. The quality of SRs was evaluated using the AMSTAR-2 tool. The GRADE system was used to assess the quality of evidence. RESULTS: Twenty-seven SRs were included. The number of included studies were various, range from 3 to 27. The condition with the most included SRs was nausea and vomiting (n = 12, 44.4%). Many SRs showed a promising efficacy of ginger, including nausea and vomiting, metabolic syndrome and pain, while the effect of ginger for platelet aggregation failed to draw a certain conclusion. The quality of SRs was heterogeneous. All of included SRs well complied with the Item 1 ("research questions included the components of PICO") and Item 3 ("explained selection of the study designs for inclusion"). Twenty review failed to provide registration information. Only one SR reported the sources of funding for studies included. CONCLUSIONS: In our overview, most of SRs suggest ginger is a promising herbal medicine for health care, which is beneficial for nausea and vomiting, metabolic syndrome and pain. However, considering the limited quality of included evidence and heterogeneity of different clinical trials, more well-design studies are required to confirm the conclusion further.

15.
Chemosphere ; 234: 318-327, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31228834

RESUMO

Although EPS in microbial aggregates are importance in successful implementation of biological wastewater treatment systems, they also exhibit detrimental role on certain circumstance, such as excess sludge dewatering. Extensive efforts have been put into the disruption of EPS for improving the dewaterability of excess sludge and Fenton's reagent treatment has been demonstrated to be a very promising sludge conditioning method for EPS destruction. However, the information regarding detailed degradation process of EPS during Fenton's reagent treatment is limited. In this study, EPS were extracted from activated sludge and treated with different concentrations of Fenton's reagent. The physicochemical characteristic changes of EPS under different treatment were investigated in terms of components, EEM, molecular weight (MW), UV-Vis and FTIR. The results showed that EPS were prone to be disintegrated, but hard to be fully mineralized. Humic substances in EPS were more resistant to Fenton's reagent than other components. Low MW components of EPS were preferentially degraded prior to the disruption of high MW components. Besides, the disintegration of EPS into lower MW ones was accompanied by the formation of higher MW compounds caused by the bridge interaction of Fe ions. The cleavage of protein's backbone in EPS was mainly through destruction of amide II (N-H and C-N) in -CO-NH-. Fenton's reagent treatment also led to a significant increase of oxygen-containing functional groups in EPS molecules. This paper may pave a path to deeply understand the mechanisms of dewatering improvements of excess sludge by Fenton's conditioning.

16.
Analyst ; 144(13): 4073-4080, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31165805

RESUMO

Ratiometric electrochemical sensors can provide a relatively accurate analysis of target analytes due to their self-calibration function. Herein, we report a simple ratiometric strategy for achieving the electrochemical detection of Cd(ii), Hg(ii), Pb(ii) and Zn(ii), as well as multiple cancer biomarkers by using metal sulfide nanoparticles as signal tags. A conductive polymer film of poly(2-amino terephthalic acid) (ATA) was electrochemically produced on a glassy carbon electrode (GCE) and doped with carbon nanotubes (CNTs) and mercaptosuccinic acid (MSA). Using Bi(iii) as an enhancer and internal reference in anodic stripping voltammetry, the MSA-CNT-ATA/GCE exhibited sensitive and distinguishable voltammetric responses to Cd(ii), Hg(ii), Pb(ii) and Zn(ii), with detection limits of 0.13, 0.49, 0.16 and 0.089 µg L-1, respectively. By using CdS, HgS, PbS and ZnS labeled secondary antibodies as the signal tags, alpha-fetoprotein, carbohydrate antigen 19-9, carbohydrate antigen 125, and carcinoembryonic antigen were determined simultaneously according to the amounts of metal sulfide in the sandwich-type complexes, with detection limits of 0.11 pg mL-1, 0.68 mU mL-1, 1.4 mU mL-1 and 0.23 pg mL-1, respectively. This ratiometric approach has a wide scope in the electrochemical detection of heavy metal ions as well as immunoassays with metal ions serving as signal tags.


Assuntos
Biomarcadores Tumorais/sangue , Bismuto/química , Nanopartículas Metálicas/química , Metais Pesados/análise , Sulfetos/química , Anticorpos/imunologia , Biomarcadores Tumorais/imunologia , Antígeno Ca-125/sangue , Antígeno Ca-125/imunologia , Antígeno CA-19-9/sangue , Antígeno CA-19-9/imunologia , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/imunologia , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Imunoensaio/métodos , Limite de Detecção , Proteínas de Membrana/sangue , Proteínas de Membrana/imunologia , Metais Pesados/química , Nanotubos de Carbono/química , Ácidos Ftálicos/química , Polímeros/química , Reprodutibilidade dos Testes , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia
17.
Biomed Res Int ; 2019: 4072319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240212

RESUMO

In retinopathy of prematurity (ROP), outer deep vascular plexus (oDVP) was the emerging field, and the mechanisms of photoreceptor dysfunction remained to be explored. ODVP and photoreceptors were related, with oDVP being part of the supplier of oxygen and nutrients to photoreceptors, while their possible relationship in ROP was not clear. TGF-beta1 has been reported indispensable in oDVP development and altered in ROP patients and animal models. We hypothesized that the TGF-beta1 alteration in rat 50/10 oxygen-induced retinopathy (OIR) model contributed to oDVP malformation and exerted consequent effects on photoreceptor development. We first explored the profile of oDVP development in rat after birth and compared the expression of TGF-beta1 and pSMAD2/3 in Normoxia and OIR groups. Afterwards, the inhibitor of the pathway, LY364947, was used to establish the OIR, OIR+LY364947, Normoxia, and Normoxia+LY364947 groups. The oDVP and photoreceptor were examined by Isolectin B4 staining, western-blot of CD31 and Rho, and electron microscopy. ODVP sprouted at postnatal day 10 (D10) and reached the edge of retina at D14. The TGF-beta1/SMAD2/3 pathway was compromised during the critical period of oDVP development. The inhibitor simulated the oDVP retardation, pericyte, and photoreceptor malformation in the Normoxia+LY364947 group and might further compromise the development of oDVP and photoreceptor in the OIR+LY364947 group. The inhibition of the TGF-beta1/SMAD2/3 pathway indicated its critical role in oDVP malformation and photoreceptor damage, suggesting a possible therapeutic target of ROP treatment.

18.
J Psychiatr Res ; 115: 165-175, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31150948

RESUMO

Bipolar disorder (BPD) is a severe mental illness characterized by fluctuations in mood states, behaviors and energy levels. Growing evidence suggests that genes associated with specific illnesses tend to interact together and encode a tight protein-protein interaction (PPI) network, providing valuable information for understanding their pathogenesis. To gain insights into the genetic and physiological foundation of BPD, we conduct the physical PPI analysis of 184 BPD risk genes distilled from genome-wide association studies and exome sequencing studies. We have identified several hub genes (CAMK2A, HSP90AA1 and PLCG1) among those risk genes, and observed significant enrichment of the BPD risk genes in certain pathways such as calcium signaling, oxytocin signaling and circadian entrainment. Furthermore, while none of the 184 genetic risk genes are "well established" BPD drug targets, our PPI analysis showed that αCaMKII (encoded by CAMK2A) had direct physical PPIs with targets (HRH1, SCN5A and CACNA1E) of clinically used anti-manic BPD drugs, such as carbamazepine. We thus speculated that αCaMKII might be involved in the cellular pharmacological actions of those drugs. Using cultured rat primary cortical neurons, we found that carbamazepine treatment induced phosphorylation of αCaMKII in dose-dependent manners. Intriguingly, previous study showed that CAMK2A heterozygous knockout (CAMK2A+/-) mice exhibited infradian oscillation of locomotor activities that can be rescued by carbamazepine. Our data, in combination with previous studies, provide convergent evidence for the involvement of CAMK2A in the risk of BPD.

19.
Neurochem Int ; 129: 104468, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31108132

RESUMO

BACKGROUND: Recent studies, mostly conducted in Western countries, showed that gut microbes are involved in the pathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate whether gut dysbiosis is relevant to the initiation and progression of MS in a Chinese population. METHODS: Next-generation sequencing (NGS) and gas chromatography (GC) were integrated and used to compare the fecal bacterial communities and the short-chain fatty acid (SCFA) levels among relapsing-remitting MS (RRMS) patients (n = 34), neuromyelitis optica spectrum disorder (NMOSD) patients (n = 34), and healthy controls (HCs) (n = 34). T-cell profile analyses were performed by flow cytometry for MS patients and matched controls (n = 12). RESULTS: (1) The gut microbiome of MS patients was characterized by an increase of Streptococcus and a decrease of Prevotella_9; additionally, compared to NMOSD patients, Prevotella_9 was found to be much more abundant in MS patients. (2) A striking depletion of fecal acetate, propionate, and butyrate was observed in MS patients compared to HCs. (3) The abundance of Streptococcus was negatively correlated with the proportion of pTregs (P < 0.05) and positively correlated with Th17 cells (P < 0.05) in the peripheral blood, while the abundance of Prevotella_9 was negatively correlated with the Th17 cell frequency (P < 0.01), and the fecal SCFA level was positively correlated with pTreg frequency (P < 0.05). CONCLUSIONS: Gut dysbiosis and a lack of SCFAs exist in Chinese MS patients, which might be related to an aberrant immune response of MS; this relationship may have a diagnostic and therapeutic value for patients with MS.

20.
Hypertens Pregnancy ; 38(2): 129-139, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30935246

RESUMO

OBJECTIVES: The purpose of this study is to investigate whether calcium supplement with or without other drugs could reduce the risk of preeclampsia and gestational hypertension based on existed evidence, and to clarify whether there is discrepant effect among different population and using different dose. METHODS: PubMed, Cochrane library, and EMBASE database were searched. Two authors independently screened all records and extracted data. The meta-analysis was performed to calculate risk ratios and 95% CIs using random-effects models. RESULTS: 27 studies, with 28 492 pregnant women were included. The results showed calcium supplement was associated with lower incidence of preeclampsia (RR 0.51, 95% CI: 0.40 to 0.64) and gestational hypertension (RR 0.70, 95% CI: 0.60 to 0.82). Sub-analyses revealed high-dose (1.2-2 g/day), moderate-dose (0.6-1.2 g/day), and low-dose (<0.6 g/day) of calcium supplement could reduce the risk of preeclampsia. For gestational hypertension, only high dose and moderate dose groups were associated with reducing the risk of gestational hypertension. However, we could draw a conclusion which does group was the most protective, as we were unable to directly compare the effects of different doses. CONCLUSIONS: This study indicated calcium supplementation might decrease the risk of preeclampsia and gestational hypertension. And results of subgroups analyses enhanced our confidence to the protective effect of calcium supplementation. However, further studies with direct comparison of different dose of calcium supplementation are needed to explore the ideal dose of calcium supplementation to prevent preeclampsia and gestational hypertension.


Assuntos
Cálcio/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
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