RESUMO
Regulatory T cells (Treg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Treg cells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a new Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.
Assuntos
Interleucina-27 , Linfócitos T Reguladores , Camundongos , Animais , Linfócitos T Auxiliares-Indutores , Tolerância Imunológica , Imunidade Celular , Células Th17RESUMO
WHAT IS KNOWN AND OBJECTIVE: Starting 1 August 2013, the eligible cholesterol level for statin reimbursement in patients with atherosclerotic cardiovascular disease (ASCVD) or cardiovascular disease (CVD)-related risk factors changed from LDL-C ≥ 130 mg/dl (or TC ≥ 200 mg/dl) to LDL-C ≥ 100 mg/dl (or TC ≥ 160 mg/dl) in Taiwan, which may modify clinician prescribing behaviours. We aimed to evaluate the impact of changing reimbursement criteria on statin treatment patterns. METHODS: A before-after cohort design was conducted using Taiwan's National Health Insurance Research Database. Differences in statin treatment patterns between the pre- and postregulation periods were compared. Two prespecified study cohorts were identified to examine the impacts of this change on those who need statins for "secondary prevention" (patients newly diagnosed with ASCVD) and those who need statins for "primary prevention" (patients newly diagnosed with CVD-related risk factors, such as diabetes mellitus [DM]). Treatment patterns measured in this study included initiation, discontinuation, switching, dose increase, dose decrease and dose maximization. RESULTS: The proportion of patients who initiated statins during the postregulation period was higher than that of patients who initiated statins during the preregulation period (eg coronary heart disease (CHD) patients, pre- vs. postregulation: 41.23% vs. 48.25%). Notably, only 30%-40% of patients initiated statin use in the postregulation period across different conditions. In addition, the proportion of patients who discontinued statins remained very high. Even in the postregulation period, more than half of CHD patients discontinued statins during the 1-year follow-up period (eg CHD patients, pre- vs. postregulation: 59.07% vs. 52.75%). WHAT IS NEW AND CONCLUSION: The new reimbursement criteria started on 1 August 2013 seemed to lower the barriers of access to the first statin prescription among patients with CHD, cerebrovascular disease (CBVD) and DM. Nevertheless, the proportion of patients who initiated statin use was suboptimal, and the proportion of patients who discontinued statins was very high in the postregulation period.
Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Reembolso de Seguro de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Taiwan/epidemiologiaRESUMO
BACKGROUND: Cinnamomum osmophloeum (indigenous cinnamon) is an endemic species in Taiwan and its twigs contain abundant A-type proanthocyanidins. C. osmophloeum twig extracts (CoTEs) were found to have α-glucosidase and α-amylase inhibitory activities in vitro. The aim of this study is to further investigate the antihyperglycemic activity of CoTEs in hyperglycemic rats. RESULTS: Hyperglycemic rats were divided into three groups and were treated orally with high-dosage CoTEs (HCO, 150 mg kg-1 ), low-dosage CoTEs (LCO, 30 mg kg-1 ) and positive control (PC, 30 mg kg-1 pioglitazone). The HCO group showed improved glucose tolerance in an oral glucose tolerance test after 1 month of treatment, contributed by the inhibition of intestinal disaccharidases, amylase, and lipase. Compared with the PC group, both the HCO and LCO groups had decreased weight of visceral fats and lower atherogenic index; while their low-density lipoprotein-cholesterol, food intake, feed efficiency, and biochemical parameters remained unchanged compared with the NC group. Furthermore, the HCO group had decreased weight gain and the LCO group had decreased serum leptin level. CONCLUSION: These results suggest that CoTE has potential antihyperglycemic activities for treating hyperglycemia without weight gain. © 2018 Society of Chemical Industry.
Assuntos
Cinnamomum/química , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperglicemia/metabolismo , Hipoglicemiantes/química , Masculino , Extratos Vegetais/química , Proantocianidinas/administração & dosagem , Proantocianidinas/análise , Ratos , EstreptozocinaRESUMO
BACKGROUND: In recent decades, there has been a growing demand for natural products with a view to using them as α-glucosidase inhibitors for reducing postprandial hyperglycemia. In this study, the hot water extract (HWE) from Chamaecyparis obtusa var. formosana (Hayata) Rehder (Cupressaceae) leaves and its soluble fractions were screened for α-glucosidase inhibition properties. The n-butanol-soluble fraction of HWE was further fractionated into 14 subfractions (B1-B14) using a Sephadex LH-20 column. The α-glucosidase-inhibitory activities and proanthocyanidin contents of all subfractions were determined. The structural characteristics of proanthocyanidins in proanthocyanidin-rich fractions were also elucidated. RESULTS: HWE produced a dose-dependent inhibition of α-glucosidase at low dose. Its IC50 value was 1.4 µg mL-1 , showing high inhibitory activity. Subfractions B7-B14 displayed powerful α-glucosidase-inhibitory activities with IC50 values ranging between 1 and 0.015 µg mL-1 and contained abundant proanthocyanidins exceeding 300 mg g-1 . The proanthocyanidins with higher mean degree of polymerization (mDP), higher proportions of procyanidin dimer (A1 or A2) and (epi)afzelechin of extension units and a lower proportion of epicatechin of terminal units displayed high α-glucosidase-inhibitory activities. CONCLUSION: Proanthocyanidins in HWE were viewed as potential natural α-glucosidase inhibitors for decreasing postprandial hyperglycemia. The results indicated that specific structural characteristics of proanthocyanidins would be required for α-glucosidase-inhibitory activity. © 2018 Society of Chemical Industry.
Assuntos
Chamaecyparis/química , Inibidores de Glicosídeo Hidrolases/química , Extratos Vegetais/química , Proantocianidinas/química , alfa-Glucosidases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Proantocianidinas/isolamento & purificação , alfa-Glucosidases/metabolismoRESUMO
BACKGROUND: Barks and twigs of common species of cinnamon with abundant proanthocyanidins are used as a spice, fold medicine or supplement. Cinnamomum osmophloeum is an endemic species in Taiwan and coumarin was not detected in the oil of the C. osmophloeum twig. The present study aimed to evaluate the relationship between the bioactivities and proanthocyanidins of C. osmophloeum twig extracts (CoTE). The n-butanol soluble fraction from CoTE was divided into 10 subfractions (F1-F10) by Sephadex LH-20 gel chromatography. The antihyperglycemic activities were examined by α-glucosidase, α-amylase and protein tyrosine phosphatase 1B inhibitory assays. Total antioxidant activities were examined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging and ferrous ion-chelating assays. RESULTS: The results revealed that subfractions F6-F10, with high proanthocyanidin contents, showed excellent antihyperglycemic and antioxidant activities. Subfractions F6-F10 were analyzed further by matrix-assisted laser desorption/ionization-time of flight/mass spectrometry and thiolysis-reversed-phase high-performance liquid chromatography/tandem mass spectrometry methods. The results showed that the mean degrees of polymerization of proanthocyanidins in subfractions F6-F10 ranged from 3.5 to 5.1, with the highest degrees of polymerization of proanthocyanidins reaching 8 in subfractions F8-F10. Two compounds in F6 were identified as cinnamtannin B1 and parameritannin A1. These proanthocyanidins contained at least one A-type and major B-type linkages. CONCLUSION: These results demonstrate that proanthocyanidins are associated with their antihyperglycemic and antioxidant activities in CoTE. © 2016 Society of Chemical Industry.
Assuntos
Cinnamomum zeylanicum/química , Proantocianidinas/química , Proantocianidinas/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenóis/química , Espectrometria de Massas por Ionização por Electrospray , alfa-Amilases/química , alfa-Amilases/farmacologiaRESUMO
Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.
Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Fase G1/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Neoplasias Pulmonares/metabolismo , Acetilação/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Desacetilase 6 de Histona , Humanos , Ácidos Hidroxâmicos/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The early microbial colonization of the gastrointestinal tract can have long-term impacts on development and health. Keystone species, including Bacteroides spp., are prominent in early life and play crucial roles in maintaining the structure of the intestinal ecosystem. However, the process by which a resilient community is curated during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa in early life and regulates a commensal colonization program. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. NanH is required for vertical transmission from dams to pups and promotes B. fragilis dominance during early life. Furthermore, NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and microbiota mediated through host-derived glycans to promote stable colonization.
Assuntos
Ecossistema , Neuraminidase , Humanos , Bacteroides fragilis , Mucosa Intestinal/microbiologia , PolissacarídeosRESUMO
Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites. IMPORTANCE: Understanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.
Assuntos
Bacteroides fragilis , Variação Genética , Genoma Bacteriano , Bacteroides fragilis/genética , Bacteroides fragilis/patogenicidade , Bacteroides fragilis/isolamento & purificação , Humanos , Genoma Bacteriano/genética , Microbioma Gastrointestinal/genética , Filogenia , Infecções por Bacteroides/microbiologia , Sequenciamento Completo do Genoma , Farmacorresistência Bacteriana/genéticaRESUMO
Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.
Assuntos
Interferon Tipo I , Interleucina-27 , Camundongos , Animais , Interleucina-27/metabolismo , Linfócitos T Reguladores , Interferon Tipo I/metabolismo , Tolerância Imunológica , Fatores de Transcrição Forkhead/metabolismo , Bactérias/metabolismo , Células DendríticasRESUMO
Bacteroides fragilis is a prominent member of the human gut microbiota, playing crucial roles in maintaining gut homeostasis and host health. Although it primarily functions as a beneficial commensal, B. fragilis can become pathogenic. To determine the genetic basis of its duality, we conducted a comparative genomic analysis of 813 B. fragilis strains, representing both commensal and pathogenic origins. Our findings reveal that pathogenic strains emerge across diverse phylogenetic lineages, due in part to rapid gene exchange and the adaptability of the accessory genome. We identified 16 phylogenetic groups, differentiated by genes associated with capsule composition, interspecies competition, and host interactions. A microbial genome-wide association study identified 44 genes linked to extra-intestinal survival and pathogenicity. These findings reveal how genomic diversity within commensal species can lead to the emergence of pathogenic traits, broadening our understanding of microbial evolution in the gut.
RESUMO
microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.
Assuntos
Metabolômica , Espectrometria de Massas em Tandem , Humanos , Metabolômica/métodos , Bases de Dados FactuaisRESUMO
OBJECTIVES: To describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in Taiwan. DESIGN: Retrospective cohort study. SETTING: This was a retrospective cohort study using Taiwan's National Health Insurance Research Database. PARTICIPANTS: In total, 111 399, 133 538 and 21 572 patients who were hospitalised with diagnosis of coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD), respectively, between 1 January 2012 and 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: For each index and recurrent event, patients were observed for 12 months after admission to quantify risks of mortality, recurrent events, statin treatment and healthcare use. RESULTS: We identified 97 321, 120 914 and 14 794 patients with new-onset CHD, CBVD and PAD, respectively. The proportions of developing first, second and third recurrent events were 22.5%, 25.6% and 30.9% for CHD; 20.9%, 26.2% and 32.4% for CBVD and 40.2%, 41.4% and 43.6% for PAD, respectively. Most patients had the same type of ASCVD for their recurrent events as their new-onset event. The mortality rates increased with each recurrent event (p<0.05 for all three ASCVD groups). The rates of hospital readmission and emergency room (ER) visit increased with increasing recurrent events. For example, in the CHD group, the 1-year readmission rates following the index, first and second recurrent events were 43.1%, 47.6% and 55.3%, respectively, and the proportions of visiting ER were 46.4%, 51.9% and 57.8%, respectively. Statin prescribing was suboptimal at time of index event and recurrent events. CONCLUSION: Recurrent ASCVD events were associated with a higher risk of recurrent event and mortality and greater healthcare use. However, statin prescriptions at index event and after each recurrent event were suboptimal.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia , Aterosclerose/epidemiologia , Atenção à Saúde , Fatores de RiscoRESUMO
The early microbial colonization of the gastrointestinal tract can lead to long-term impacts in development and overall human health. Keystone species, including Bacteroides spp ., play a crucial role in maintaining the structure, diversity, and function of the intestinal ecosystem. However, the process by which a defined and resilient community is curated and maintained during early life remains inadequately understood. Here, we show that a single sialidase, NanH, in Bacteroides fragilis mediates stable occupancy of the intestinal mucosa and regulates the commensal colonization program during the first weeks of life. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. After examining the dynamics between pioneer gut Bacteroides species in the murine gut, we discovered that NanH enables vertical transmission from dams to pups and promotes B. fragilis dominance during early life. Furthermore, we demonstrate that NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and the microbiota mediated through host-derived glycans to promote stable intestinal colonization.
RESUMO
Regulatory T (Treg) cells are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, here we show that IL-27 is specifically produced by intestinal Treg cells to regulate Th17 immunity. Selectively increased intestinal Th17 responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+TCF1+ Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a novel Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue, and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.
RESUMO
Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon that differentiates into two genomospecies termed division I and II. We leverage a comprehensive collection of 694 B. fragilis whole genome sequences and report differential gene abundance to further support the recent proposal that divisions I and II represent separate species. In division I strains, we identify an increased abundance of genes related to complex carbohydrate degradation, colonization, and host niche occupancy, confirming the role of division I strains as gut commensals. In contrast, division II strains display an increased prevalence of plant cell wall degradation genes and exhibit a distinct geographic distribution, primarily originating from Asian countries, suggesting dietary influences. Notably, division II strains have an increased abundance of genes linked to virulence, survival in toxic conditions, and antimicrobial resistance, consistent with a higher incidence of these strains in bloodstream infections. This study provides new evidence supporting a recent proposal for classifying divisions I and II B. fragilis strains as distinct species, and our comparative genomic analysis reveals their niche-specific roles.
RESUMO
MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.
RESUMO
The current investigation attempted to confirm the beneficial actions of a chemically characterized Radix Astragali decoction (AM-W) against type 2 diabetic (T2D) Sprague-Dawley (SD) rats. Using a case/control design, after 2 months of treatment with AM-W (500 mg/kg, daily i.p.) in T2D rats therapeutic outcomes were compared. Sucrose and Astragalus polysaccharides (ASPs) were shown to exist in nearly equal proportions in AM-W. Body weight loss, an improvement in insulin sensitivity, and an attenuation of fatty liver after AM-W administration in T2D rats were evident. Surprisingly, blood sugar, beta-cell function, and glucose tolerance in T2D rats did not improve with AM-W treatment. Further investigation indicated the deleterious effects of the addition of sucrose (100 and 500 µg/mL) and APSs (500 µg/mL) on glucose-stimulated insulin secretion and viability, respectively. In conclusion, a proper administration dosage and a reduction in the sucrose content are keys to maximizing the merits of this herb.
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"Real-world" data on the nationwide epidemiology and treatment patterns of multiple sclerosis (MS) is very scarce in Asia. This study is aim to evaluate the 10-years trends in epidemiology and treatment patterns of MS with Taiwan's National Health Insurance Database (NHIRD). Patients aged 20 years or older and were newly diagnosed with MS between 2007 and 2016 were identified. The crude incidences of MS were presented annually and stratified by sex and age. Baseline characteristics and treatment patterns, particularly disease-modifying drugs (DMDs), were also analyzed. This study included 555 MS patients (mean age was 36.9 and 74.4% were female). The crude incidence rate of MS decreased slightly from 0.43 per 100,000 persons in 2007 to 0.24 per 100,000 persons in 2015. The female to male ratios remained mainly between 2 to 3. Approximately 80% of MS patients received initial DMDs, with interferon ß-1a as the dominant one. Furthermore, 37.5% of MS patients received subsequent DMDs, with fingolimod being the most frequently used. The median times from diagnosis to initial and to subsequent DMDs were 77 and 1239 days, respectively. This nationwide study provides up-to-date and sophisticated estimates of MS epidemiology and treatment pattern in "real-world" setting in Taiwan.
Assuntos
Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Taiwan/epidemiologia , Adulto JovemRESUMO
Chamaecyparis obtusa var. formosana is a species indigenous to Taiwan and has been used as a medicinal plant. It has been claimed that the hot water extracts of C. obtusa var. formosana leaves (CoLE) with flavonoids and proanthocyanidins have anti-oxidant and anti-hyperglycemic activities in vitro. This study further examines the anti-hyperglycemic activity of CoLE and its possible mechanisms in hyperglycemic rats. Hyperglycemia of rats was induced by streptozotocin (STZ) and high-fat diets (HFD). Hyperglycemic rats treated orally with 30 and 150 mg/kg CoLE were classified into LCO and HCO groups, respectively. After three-month treatment, both LCO and HCO groups showed improved glucose metabolism in oral glucose tolerance and postprandial blood glucose tests. Decrease in HOMA-IR, leptin and adiponectin levels of the HCO group revealed amelioration of insulin and leptin resistance. Obesity and accumulation of visceral fats induced by STZ and HFD could be alleviated in both HCO and LCO groups. These anti-diabetic effects might be contributed by inhibition of intestinal digested enzymes and protein tyrosine phosphatases (PTPases). Although other studies are necessary, these findings suggest that CoLE could be potentially used as a health complement for treating diabetes without significant toxicity.
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Metastasis is the crucial mechanism to cause high mortality in lung cancer. Degradation of extracellular matrix (ECM) by proteolytic enzymes, especially matrix metalloproteinases (MMPs), is a key process for promoting cancer cell migration and invasion. Therefore, targeting MMPs might be a strategy for lung cancer metastasis suppression. Honokiol, a biological active component of Magnolia officinalis, has been indicated to suppress lung cancer tumorigenesis through epigenetic regulation. However, the regulation of MMPs-mediated migration and invasion by honokiol through epigenetic regulation in lung cancer is still a mystery. In the present study, the migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment. The proteolytic activity of MMP-9, rather than MMP-2, was inhibited in honokiol-treated H1299 cells. Honokiol-inhibited MMP-9 expression was through promoting MMP-9 protein degradation rather than suppressing transcription mechanism. Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl-α-tubulin, was accumulated after honokiol incubation. The disassociation of MMP-9 with hyper-acetylated heat shock protein 90 (Hsp90) was observed resulting in MMP-9 degradation after honokiol treatment. Meanwhile, honokiol-suppressed MMP-9 expression and invasion ability of H1299 lung cancer cells was rescued by HDAC6 overexpression. Accordingly, the results suggested that the suppression of migration and invasion activities by honokiol was through inhibiting HDAC6-mediated Hsp90/MMP-9 interaction and followed by MMP-9 degradation in lung cancer.