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1.
Molecules ; 29(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38675708

RESUMO

Dragon's blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) to prepare a series of DB-MSN composites (5DB-MSN, 10DB-MSN, and 20DB-MSN). DB-MSN could quickly release DB and activate the intrinsic blood coagulation cascade simultaneously by DB and MSN. Hemostasis tests demonstrated that DB-MSN showed superior hemostatic effects than either DB or MSNs alone, and 10DB-MSN exhibited the best hemostatic effect. In addition, the antibacterial activities of DB-MSN against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) improved with the increase in DB. Furthermore, the hemolysis assay and cytocompatibility assay demonstrated that all DB-MSNs exhibited excellent biocompatibility. Based on these results, 10DB-MSN is expected to have potential applications for emergency hemostatic and antibacterial treatment in pre-hospital trauma.


Assuntos
Antibacterianos , Escherichia coli , Hemostasia , Hemostáticos , Nanopartículas , Extratos Vegetais , Dióxido de Silício , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Dióxido de Silício/química , Nanopartículas/química , Escherichia coli/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Porosidade , Animais , Hemólise/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Humanos , Dracaena/química , Camundongos , Testes de Sensibilidade Microbiana
2.
Nat Prod Res ; 38(1): 103-111, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-35929965

RESUMO

ABSTACTA chemical investigation of the endophyte Penicillium sp. Nb 19, isolated from leaves of the traditionally medical plant Baphicacanthus cusia (Nees) Bremek., yielded one new indole diterpenoid, 7-methoxy-13-dehydroxypaxilline (1) together with seven known metabolites (2-8). The obtained structure of compound 1 was elucidated by its spectroscopic data. In addition, the absolute configuration of compound 6 was confirmed by ECD for the first time. Compounds 1-6 were evaluated for antitumor activity against MCF-7, HepG2, and HCCC-9810 cell lines.


Assuntos
Diterpenos , Penicillium , Nióbio/metabolismo , Diterpenos/química , Fungos , Indóis/química , Penicillium/química , Estrutura Molecular
3.
Front Public Health ; 11: 1235304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37732094

RESUMO

Acute poisoning is a significant public health concern. This retrospective study investigates trends in acute poisoning cases and explores the clinical and sociodemographic profiles associated with this condition. Medical data from 859 hospitalized patients diagnosed with acute poisoning between January 2017 and December 2022 were comprehensively analyzed. The descriptive statistical analysis revealed that 360 patients had underlying diseases, with depression being the most prevalent among them. Furthermore, urban areas accounted for 87.2% of the acute poisoning cases, indicating a higher incidence compared to rural areas. The substances implicated in acute poisoning incidents varied, with drugs of abuse being the most common (53.2%), followed by pesticides (22.2%), carbon monoxide (11.8%), and alcohol (5.4%). Suicide attempt/suicide emerged as the leading cause of acute poisoning incidents, accounting for 75.9% of cases, while poisoning accidents predominantly occurred within the home setting. Through chi-square tests, it was determined that risk factors for suicide attempt/suicide included female gender and underlying medical conditions. Temporal analysis showed that the total number of acute poisoning cases increased from 2017 to 2019 and decreased from 2019 to 2022. Notably, suicide-related cases exhibited an upward trend, with suicide attempt/suicide accounting for over 80% of all acute poisoning cases after 2020. This study contributes valuable insights into the trends, profiles, and risk factors associated with acute poisoning cases.


Assuntos
Praguicidas , Humanos , Feminino , Estudos Retrospectivos , Etanol , Saúde Pública
4.
Ticks Tick Borne Dis ; 14(4): 102193, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37150103

RESUMO

Theileria equi is a tick-borne intracellular apicomplexan protozoan parasite that causes equine theileriosis (ET). ET is an economically important disease with a worldwide distribution that significantly impacts international horse movement. Horses are an essential part of the economy in Xinjiang which is home to ∼10% of all the horses in China. However, there is very limited information on the prevalence and genetic complexity of T. equi in this region. Blood samples from 302 horses were collected from May to September 2021 in Ili, Xinjiang, and subjected to PCR examination for the presence of T. equi. In addition, a Bayesian latent class model was employed to estimate the true prevalence of T. equi, and a phylogenetic analysis was carried out based on the 18S rRNA gene of T. equi isolates. Seventy-two horses (23.8%) were PCR positive. After accounting for the imperfect PCR test using a Bayesian latent class model, the estimated true prevalence differed considerably between age groups, being 10.8% (95%CrI: 5.8% - 17.9%) in ≤ 3-year-old horses and 35.7% (95%CrI: 28.1% - 44.5%) in horses that were > 3 year-old. All T. equi isolates had their 18S rRNA gene (430bp) sequenced and analyzed in order to identify whether there were multiple genotypes of T. equi in the Xinjiang horse population. All of the 18S rRNA genes clustered into one phylogenetic group, clade E, which is thus probably the dominant genotype of T. equi in Xinjiang, China. To summarize, we monitored the prevalence of T. equi in horses of Xinjiang, China, with a focus on the association between age and the occurrence of T. equi by Bayesian modelling, accompanied by the genotyping of T. equi isolates. Obtaining the information on genotypes and age structure is significant in monitoring the spread of T. equi and studying the factors responsible for the distribution.


Assuntos
Babesiose , Doenças dos Cavalos , Theileria , Theileriose , Bovinos , Cavalos , Animais , Prevalência , Filogenia , Teorema de Bayes , Theileriose/parasitologia , Variação Genética , Doenças dos Cavalos/diagnóstico , Babesiose/epidemiologia
5.
Sci Rep ; 13(1): 3816, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882618

RESUMO

Resina Draconis (RD) is known as the "holy medicine for promoting blood circulation" and possesses antitumor properties against various types of cancer, including breast cancer (BC); however, the underlying mechanism is not well understood. To explore the potential mechanism of RD against BC using network pharmacology and experimental validation, data on bioactive compounds, potential targets of RD, and related genes of BC were obtained from multiple public databases. Gene Ontology (GO) and KEGG pathway analyses were performed via the DAVID database. Protein interactions were downloaded from the STRING database. The mRNA and protein expression levels and survival analysis of the hub targets were analyzed using the UALCAN, HPA, Kaplan‒Meier mapper, and cBioPortal databases. Subsequently, molecular docking was used to verify the selected key ingredients and hub targets. Finally, the predicted results of network pharmacology methods were verified by cell experiments. In total, 160 active ingredients were obtained, and 148 RD target genes for the treatment of BC were identified. KEGG pathway analysis indicated that RD exerted its therapeutic effects on BC by regulating multiple pathways. Of these, the PI3K-AKT pathway was indicated to play an important role. In addition, RD treatment of BC seemed to involve the regulation of hub targets that were identified based on PPI interaction network analysis. Validation in different databases showed that AKT1, ESR1, HSP90AA1, CASP3, SRC and MDM2 may be involved in the carcinogenesis and progression of BC and that ESR1, IGF1 and HSP90AA1 were correlated with worse overall survival (OS) in BC patients. Molecular docking results showed that 103 active compounds have good binding activity with the hub targets, among which flavonoid compounds were the most important active components. Therefore, the sanguis draconis flavones (SDF) were selected for subsequent cell experiments. The experimental results showed that SDF significantly inhibited the cell cycle and cell proliferation of MCF-7 cells through the PI3K/AKT pathway and induced MCF-7 cell apoptosis. This study has preliminarily reported on the active ingredients, potential targets, and molecular mechanism of RD against BC, and RD was shown to exert its therapeutic effects on BC by regulating the PI3K/AKT pathway and related gene targets. Importantly, our work could provide a theoretical basis for further study of the complex anti-BC mechanism of RD.


Assuntos
Neoplasias da Mama , Extratos Vegetais , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proliferação de Células , Células MCF-7 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Extratos Vegetais/farmacologia
6.
JAMA Netw Open ; 5(9): e2230439, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36169959

RESUMO

Importance: With few approved multiple sclerosis therapies in the pediatric population, there is a need for further approved treatment options. Limited data exist for dimethyl fumarate (DMF) treatment in pediatric-onset multiple sclerosis (POMS). Objective: To compare the efficacy, safety, and tolerability of DMF vs intramuscular interferon ß-1a (IFNß-1a) in POMS. Design, Setting, and Participants: The CONNECT study was an active-controlled, open-label, rater-blinded 96-week randomized clinical trial in patients with POMS aged 10 to less than 18 years treated between August 2014 and November 2020. Data were analyzed from January through October 2021. Interventions: Patients were randomized to DMF or IFNß-1a. Main Outcomes and Measures: The primary end point was the proportion of patients free of new or newly enlarging (N or NE) T2 hyperintense lesions at week 96 among trial completers. Secondary end points included number of N or NE T2 lesions, proportion of patients free of relapse, annualized relapse rate (ARR), and safety. The estimated proportion of participants who were relapse free up to week 96 was calculated based on the Kaplan-Meier method. Adjusted ARR was obtained from a negative binomial regression adjusted for baseline relapse rate, baseline Expanded Disability Status Scale (EDSS) score, and age group. Results: Among 150 patients with POMS in the intention-to-treat (ITT) population (median [range] age, 15 [10-17] years; 101 [67.3%] female patients), 78 individuals received DMF and 72 individuals received IFNß-1a. At week 96, the proportion of patients with no N or NE T2 hyperintense lesions among 103 trial completers was 16.1% (95% CI, 8.0%-27.7%) for DMF vs 4.9% (95% CI, 0.6%-16.5%) for IFNß-1a, and in a sensitivity analysis among the ITT population, the proportions were 10 patients receiving DMF (12.8%) vs 2 patients receiving IFNß-1a (2.8%). The estimated proportion of patients who remained relapse free at week 96 was 66.2% for DMF vs 52.3% for IFNß-1a. Adjusted ARR (95% CI) at week 96 was 0.24 (95% CI, 0.15-0.39) for DMF vs 0.53 (95% CI, 0.33-0.84) for IFNß-1a; the rate ratio for DMF vs IFNß-1a was 0.46 (95% CI, 0.26-0.80; P = .006). The number of treatment-emergent adverse events (TEAEs; 74 patients [94.9%] vs 69 patients [95.8%]), serious TEAEs (18 patients [23.1%] vs 21 patients [29.2%]), and treatment discontinuations due to TEAEs (5 patients [6.4%] vs 8 patients [11.1%]) was similar for DMF vs IFNß-1a. Conclusions and Relevance: This study found that more pediatric patients with POMS treated with DMF were free of new or newly enlarging T2 lesions and that the adjusted ARR was lower among these patients compared with those treated with interferon ß-1a. DMF was well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT02283853.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adolescente , Criança , Fumarato de Dimetilo/uso terapêutico , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Interferon beta/efeitos adversos , Interferon beta/uso terapêutico , Masculino , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
7.
Front Microbiol ; 13: 930981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722281

RESUMO

The Beibu Gulf harbors abundant underexplored marine microbial resources, which are rich in diversified secondary metabolites. The genera Vibrio is a well-known pathogenic bacterium of aquatic animals. In this study, 22 fungal strains were isolated and identified from the Beibu Gulf coral via the serial dilution method and internal transcribed spacer (ITS) sequence analysis, which were further divided into three branches by phylogenetic tree analysis. The crude extracts of them via small-scale fermentation were selected for the screening of inhibitory activity against Vibrio alginalyticus, Vibrio coralliilyticus, Vibrio harveyi, Vibrio parahaemolyticus, Vibrio owensii, and Vibrio shilonii. The results showed that eight fungal extracts displayed anti-Vibrio activity via the filter paper disk assay. Several of them showed strong inhibitory effects. Then, two tetramic acid alkaloids, equisetin (1) and 5'-epiequisetin (2), were identified from Fusarium equiseti BBG10 by bioassay-guided isolation, both of which inhibited the growth of Vibrio spp. with the MIC values of 86-132 µg/ml. The scanning electron microscope results showed that cell membranes of Vibrio became corrugated, distorted or ruptured after treatment with 1 and 2. Taken together, this study provided eight fungal isolates with anti-Vibrio potentials, and two alkaloid-type antibiotics were found with anti-Vibrio effects from the bioactive strain F. equiseti BBG10. Our findings highlight the importance of exploring promising microbes from the Beibu Gulf for the identification of anti-Vibrio for future antibiotic development.

8.
Neoplasma ; 69(3): 657-669, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35293765

RESUMO

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality, and significant heterogeneity among patients. In this study, we aimed to explore the role and mechanism of CLK2 in CRC, a kinase that phosphorylates SR proteins involved in splicing. Based on the analysis from The Cancer Genome Atlas (TCGA) dataset and tissue microarray, we found that CLK2 was upregulated in CRC tissues and associated with a higher tumor stage and poorer overall survival. Consistent with the bioinformatics analysis, the functional experiments validated that CLK2 acted as a tumor-promoting factor in CRC progression. CLK2 knockdown suppressed aggressive cell proliferation, migration, and invasion in vitro, as well as restrained tumor growth in vivo. In terms of mechanism, we found that the Wnt/ß-catenin signaling pathway was responsible for the CLK2-induced CRC progression, based on the results of pathway enrichment analysis and subsequent experimental validation. Thus, our study, for the first time, identified the role of CLK2 in CRC development and provided a compelling biomarker for targeted therapy in CRC treatment.


Assuntos
Neoplasias Colorretais , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases , Via de Sinalização Wnt , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Centers for Disease Control and Prevention, U.S. , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Estados Unidos , Via de Sinalização Wnt/genética , beta Catenina/metabolismo
9.
Front Public Health ; 10: 979238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36711413

RESUMO

Aim: The purpose of this study was to evaluate the effectiveness of the graded transport mode in the intrahospital transport (IHT) of critically ill patients. Methods: This is a retrospective study, including 800 patients and categorized them into control and observation groups. The control group included 420 critically ill patients who were transported via conventional methods from our emergency resuscitation unit from June 2017 to December 2017. The observation group included 380 critically ill patients who were transported through a graded transport mode from January 2018 to June 2018. We performed intergroup comparisons of the incidence rates and causes of adverse events (AEs), transport time, length of stay, and mortality rate. Results: The observation group had significantly lower transport time and AE incidence rates than the control group. However, no significant differences were observed in terms of the length of stay and mortality rate between the two groups. Conclusion: The most notable merits of the graded transport mode in the IHT of critical care patients include the fact that it significantly reduces the incidence of AEs during IHT, shortens the transport time, and improves transport efficiency, thereby ensuring the safety of critically ill patients.


Assuntos
Estado Terminal , Unidades de Terapia Intensiva , Humanos , Estudos Retrospectivos , Cuidados Críticos/métodos , Respiração Artificial/efeitos adversos
10.
Artigo em Inglês | MEDLINE | ID: mdl-36612927

RESUMO

People-oriented development has become the main theme of China's current social development, and the construction of various urban infrastructure has shifted from a focus on functionalism to a continuous pursuit of service quality. As an essential infrastructure for urban transport, urban parking facilities have an impact on pedestrian experience and landscape appearance based on the provision of parking functions. Therefore, this study is oriented to improving the quality of parking facilities, proposes a research framework of parking facilities based on meeting functional demand and service quality, and constructs a quality index to evaluate the quality of parking facilities, which includes three dimensions of evaluation indexes: pedestrian space impact, environmental space impact, and demand matching. By analyzing the current characteristics of urban parking facilities and measuring their quality index (6.5), the study finds that while satisfying the basic function of parking demand, it brings a negative impact on the pedestrian experience and the overall urban landscape appearance of the city. Motivated by this, this study proposes strategies to improve the quality of parking facilities: demand matching, spatial synergy, and environmental design to address parking difficulties, while injecting different ideas for future value orientation of parking facility planning and construction.


Assuntos
Estacionamentos , Pedestres , Humanos , Melhoria de Qualidade , China , Cidades
11.
Front Pharmacol ; 12: 772504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819865

RESUMO

Background: The prevalence of hyperuricemia is considered high worldwide. Hyperuricemia occurs due to decreased excretion of uric acid, increased synthesis of uric acid, or a combination of both mechanisms. There is growing evidence that hyperuricemia is associated with a decline of renal function. Purpose: This study is aimed at investigating the effects of the novel compound on lowering the serum uric acid level and alleviating renal inflammation induced by high uric acid in hyperuricemic mice. Methods: Hyperuricemic mice model was induced by potassium oxonate and used to evaluate the effects of the novel compound named FxUD. Enzyme-linked immunosorbent assay was used to detect the related biochemical markers. Hematoxylin-eosin (HE) staining was applied to observe pathological changes. The mRNA expression levels were tested by qRT-PCR. The protein levels were determined by Western blot. In parallel, human proximal renal tubular epithelial cells (HK-2) derived from normal kidney was used to further validate the anti-inflammatory effects in vitro. Results: FxUD administration significantly decreased serum uric acid levels, restored the kidney function parameters, and improved the renal pathological injury. Meanwhile, treatment with FxUD effectively inhibited serum and liver xanthine oxidase (XOD) levels. Reversed expression alterations of renal inflammatory cytokines, urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were observed in hyperuricemic mice. Western blot results illustrated FxUD down-regulated protein levels of inflammasome components. Further studies showed that FxUD inhibited the activation of NF-κB signaling pathway in the kidney of hyperuricemic mice. In parallel, the anti-inflammatory effect of FxUD was also confirmed in HK-2. Conclusion: Our study reveals that FxUD exhibits the anti-hyperuricemic and anti-inflammatory effects through regulating hepatic XOD and renal urate reabsorption transporters, and suppressing NF-κB/NLRP3 pathway in hyperuricemia. The results provide the evidence that FxUD may be potential for the treatment of hyperuricemia with kidney inflammation.

12.
Plant Physiol Biochem ; 156: 323-332, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32998099

RESUMO

Purple-fleshed sweetpotato (PFSP) accumulates high amounts of anthocyanins that are beneficial to human health. Although biosynthesis of such secondary metabolites has been well studied in aboveground organs of many plants, the mechanisms underlying anthocyanin accumulation in underground tuberous roots of sweetpotato are less understood. To identify genes and metabolites involved in anthocyanin accumulation in sweetpotato, we performed comparative transcriptomic and metabolomic analysis of (PFSP) and white-fleshed sweetpotato (WFSP). Anthocyanin-targeted metabolome analysis revealed that delphinidin, petunidin, and rosinidin were the key metabolites conferring purple pigmentation in PFSP as they were highly enriched in PFSP but absent in WFSP. Transcriptomic analysis identified 358 genes that were potentially implicated in multiple pathways for the biosynthesis of anthocyanins. Although most of the genes were previously known for their roles in anthocyanin biosynthesis, we identified 26 differentially expressed genes that are involved in Aux/IAA-ARF signaling. Gene-metabolite correlation analysis also revealed novel genes that are potentially involved in the anthocyanin accumulation in sweetpotato. Taken together, this study provides insights into the genes and metabolites underlying anthocyanin enrichment in underground tuberous roots of sweetpotato.


Assuntos
Antocianinas/biossíntese , Ipomoea batatas , Metaboloma , Raízes de Plantas/metabolismo , Transcriptoma , Regulação da Expressão Gênica de Plantas , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Pigmentação
13.
Zhongguo Zhong Yao Za Zhi ; 45(14): 3467-3474, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726063

RESUMO

Resin-containing drugs in Dracaena from four different appearances were analyzed by headspace sampling-gas chromatography-mass spectrometry(HS-GC-MS) metabolomics technique and hierarchical clustering analysis(HCA) chemometrics method. This study was to analyze differential volatile components in resin-containing drugs in Dracaena from different appearance and metabolic pathways. The results of partial least squares discriminant analysis(PLS-DA) and HCA analysis indicated that there was little difference in volatile components between fiber-rich sample and hollow cork cambium sample, however, the volatile components in the two samples compared with whole body resin-containing sample and resin-secreting aggregated sample had a large metabolic difference. Twenty differential metabolites were screened by VIP and P values of PLS-DA. The content of these differential metabolites was significantly higher in whole body resin-containing sample and resin-secreting aggregated sample than in fiber-rich sample and hollow cork cambium sample. Sixteen significant metabolic pathways were obtained through enrichment analysis(P<0.05), mainly involved in terpenoids biosynthesis and phenylpropanoid metabolism. This result provided a reference for further study of resin formation mechanism of resin-containing drugs in Dracaena from different appearances. At the same time, it also provided a reference for establishing a multi-index quality evaluation system.


Assuntos
Dracaena , Análise por Conglomerados , Análise Discriminante , Cromatografia Gasosa-Espectrometria de Massas , Resinas Vegetais
14.
Plant Physiol Biochem ; 154: 379-386, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32623093

RESUMO

Sweetpotato (Ipomoea batatas. L) is an important food crop, harvested for its nutrient-rich tuberous roots. Drought and salt stresses are two major factors limiting the sweetpotato production. Since microRNAs (miRNAs) are well known to play crucial roles in regulation of plant stress responses, quantitative profiling of miRNA expression under stress conditions will facilitate identification and genetic manipulation of novel miRNAs to improve stress tolerance. Real-time quantitative reverse transcription PCR (qRT-PCR) is a commonly used tool for this purpose, but not without challenges. Although stem-loop and poly(A)-tail modified qRT-PCR methods were developed for characterizing miRNA expression, accurate profiling of miRNAs is still difficult in many plant species because of a lack of reliable reference genes for normalizing miRNA transcripts. To identify reference genes that are suitable for normalizing miRNA expression in sweetpotato, the expression stability of eight candidate miRNAs and two commonly used reference genes were tested in 96 samples involving four tissues and two cultivars under drought and salt stress treatments. Data analysis using the geNorm, NormFinder and Bestkeeper algorithms demonstrated that miRn60, miR482, and their combination were reliable references. We further validated the reference genes by expression analysis of the well-characterized miR319 and miR156 that regulate drought and salt stress responses, respectively. The reference genes identified in this study will facilitate future miRNA analysis under abiotic stress conditions in sweetpotato.


Assuntos
Regulação da Expressão Gênica de Plantas , Ipomoea batatas , MicroRNAs/genética , Estresse Fisiológico , Perfilação da Expressão Gênica , Ipomoea batatas/genética , RNA de Plantas/genética , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Transcrição Reversa
15.
Mult Scler ; 26(13): 1729-1739, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31680631

RESUMO

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing-remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF's distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. OBJECTIVE: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. METHODS: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. RESULTS: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1-98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13-0.20). CONCLUSION: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Fumarato de Dimetilo/efeitos adversos , Fumaratos , Humanos , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
16.
Neurology ; 92(15): e1724-e1738, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30918100

RESUMO

OBJECTIVE: To assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis. METHODS: Using peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed. RESULTS: In DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses. CONCLUSIONS: DMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients. TRIAL REGISTRATION NUMBERS: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770.


Assuntos
Fumarato de Dimetilo/uso terapêutico , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/sangue , Adulto , Linfócitos B/efeitos dos fármacos , Relação CD4-CD8 , Estudos Transversais , Preparações de Ação Retardada , Fumarato de Dimetilo/efeitos adversos , Fumarato de Dimetilo/farmacologia , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Estudos Longitudinais , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Medição de Risco , Linfócitos T/efeitos dos fármacos
17.
Patient Prefer Adherence ; 12: 1273-1278, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050289

RESUMO

BACKGROUND: The objective of this study was to evaluate the impact of pharmaceutical care on the knowledge, adherence, and efficacy of hormone therapy in climacteric women participated in multidisciplinary collaborative clinic, launched by Peking University First Hospital (Beijing, People's Republic of China) in 2012. METHODS: A total of 296 patients were recruited (intervention group n=150, control group n=146). The patients in the intervention group visited the multidisciplinary collaborative clinic for their initial hormone therapy, receiving individualized pharmaceutical care (PC), whereas the control group visited only the general clinic without PC. The pill count method, knowledge assessment questionnaire (Cronbach's α=0.80), and the modified Kupperman Index were used to assess the knowledge, adherence, and efficacy at months 3, 6, and 12. RESULTS: The intervention group, which received PC, showed significantly higher and better knowledge, adherence, and efficacy than the control group, demonstrating the effectiveness of the PC provided. The knowledge scores of the intervention and control groups at months 3, 6, and 12 were (73.12 vs 59.28), (77.63 vs 66.19), and (80.81 vs 66.64); the data for adherence were (90.97% vs 82.17%), (93.21% vs 87.79%), and (95.81% vs 93.38%); and the values of the modified Kupperman Index were (17.15 vs 24.05), (13.22 vs 22.01), and (12.21 vs 23.15), respectively. CONCLUSION: PC improved the knowledge, adherence, and efficacy of hormone therapy in climacteric women. Therefore, the multidisciplinary collaborative model investigated in our study should be advocated in other health care institutions for the benefit of more patients. Further large-sample and long-term studies should be conducted to evaluate the effects of PC on patient clinical outcomes, including its impact on the safety and efficacy of long-term use of hormone therapy, as well as the economic benefits.

18.
Neurol Neuroimmunol Neuroinflamm ; 5(1): e409, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29159204

RESUMO

OBJECTIVES: To investigate the immune response to vaccinations in patients with relapsing forms of MS treated with delayed-release dimethyl fumarate (DMF) vs nonpegylated interferon (IFN). METHODS: In this open-label, multicenter study, patients received 3 vaccinations: (1) tetanus-diphtheria toxoid (Td) to test T-cell-dependent recall response, (2) pneumococcal vaccine polyvalent to test T-cell-independent humoral response, and (3) meningococcal (groups A, C, W-135, and Y) oligosaccharide CRM197 conjugate to test T-cell-dependent neoantigen response. Eligible patients were aged 18-55 years, diagnosed with relapsing-remitting MS (RRMS), and either treated for ≥6 months with an approved dose of DMF or for ≥3 months with an approved dose of nonpegylated IFN. Primary end point was the proportion of patients with ≥2-fold rise in antitetanus serum IgG levels from prevaccination to 4 weeks after vaccination. RESULTS: Seventy-one patients (DMF treated, 38; IFN treated, 33) were enrolled. The mean age was 45.3 years (range 27-55); 86% were women. Responder rates (≥2-fold rise) to Td vaccination were comparable between DMF- and IFN-treated groups (68% vs 73%). Responder rates (≥2-fold rise) were also similar between DMF- and IFN-treated groups for diphtheria antitoxoid (58% vs 61%), pneumococcal serotype 3 (66% vs 79%), pneumococcal serotype 8 (95% vs 88%), and meningococcal serogroup C (53% vs 53%), all p > 0.05. In a post hoc analysis, no meaningful differences were observed between groups in the proportion of responders when stratified by age category or lymphocyte count. CONCLUSIONS: DMF-treated patients mount an immune response to recall, neoantigens, and T-cell-independent antigens, which was comparable with that of IFN-treated patients and provided adequate seroprotection. CLINICALTRIALSGOV IDENTIFIER: NCT02097849. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with RRMS treated with DMF respond to vaccinations comparably with IFN-treated patients.

19.
Vet Parasitol ; 244: 111-113, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28917300

RESUMO

In order to found the epidemiological situation of T. equi in the horse herds in Ili Prefecture of Xinjiang Province, 723 blood samples collected from 4 counties and districts were test for T. equi through microscopic detection and Polymerase chain Reaction (PCR). In the result, we found that the 295 of 723 blood samples (40.8%) were positive for T. equi infection. The results showed that the choosed counties have a varying degrees infection. To our knowledge, this is the first time that we detected T. equi infection using the molecular techniques from Ili in Xinjiang Uygur Autonomous region.


Assuntos
Doenças dos Cavalos/epidemiologia , Theileria/isolamento & purificação , Theileriose/epidemiologia , Animais , China/epidemiologia , Estudos Epidemiológicos , Doenças dos Cavalos/parasitologia , Cavalos , Reação em Cadeia da Polimerase/veterinária , Theileria/genética , Theileriose/parasitologia
20.
Ther Adv Neurol Disord ; 10(1): 41-50, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28450894

RESUMO

BACKGROUND: In the pivotal phase III 2-year ADVANCE study, subcutaneous peginterferon beta-1a 125 mcg every 2 weeks demonstrated significant improvements in clinical outcomes, including disability endpoints, in patients with relapsing-remitting multiple sclerosis (RRMS). Here, we aim to further evaluate disability data from ADVANCE, and explore associations between confirmed disability progression (CDP), functional status, and health-related quality of life (HRQoL). METHODS: In total, 1512 patients were randomized to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks. After 1 year, patients on placebo were re-randomized to peginterferon beta-1a every 2 or 4 weeks. CDP was defined as ⩾1.0 point increase from a baseline Expanded Disability Status Scale (EDSS) score ⩾ 1.0, or ⩾1.5-point increase from baseline 0, confirmed 12 or 24 weeks after onset. RESULTS: Peginterferon beta-1a every 2 weeks significantly reduced risk of 12- and 24-week CDP at 1 year compared with placebo (12-week CDP: 6.8% versus 10.5%, p = 0.038; 24-week CDP: 4% versus 8.4%, p = 0.0069, peginterferon beta-1a every 2 weeks versus placebo, respectively). Benefits were maintained over 2 years (11.2% and 7.7%, peginterferon beta-1a every 2 weeks in 12- and 24-week CDP, respectively). Approximately 90% of patients with 24-week CDP had simultaneous worsening by ⩾1 point in at least one functional system score, most commonly pyramidal. Displaying a 24-week CDP was associated with worse scores on the Multiple Sclerosis Functional Composite (MSFC) scale and several HRQoL instruments; the impact of CDP was attenuated by treatment with peginterferon beta-1a every 2 weeks. CONCLUSIONS: Peginterferon beta-1a has the potential to prevent/delay worsening of disability in patients with relapsing-remitting multiple sclerosis. Furthermore, improved benefits in disability status with peginterferon beta-1a were also associated with improved functional status and HRQoL [ClinicalTrials.gov identifier: NCT00906399].

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