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1.
Mol Phylogenet Evol ; 158: 107083, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33516804

RESUMO

As a consequence of hybridization, polyploidization, and apomixis, the genus Cotoneaster (Rosaceae) represents one of the most complicated and controversial lineages in Rosaceae, with ca. 370 species which have been classified into two subgenera and several sections, and is notorious for its taxonomic difficulty. The infrageneric relationships and taxonomy of Cotoneaster have remained poorly understood. Previous studies have focused mainly on natural hybridization involving only several species, and phylogeny based on very limited markers. In the present study, the sequences of complete chloroplast genomes and 204 low-copy nuclear genes of 72 accessions, representing 69 species as ingroups, were used to conduct the most comprehensive phylogenetic analysis so far for Cotoneaster. Based on the sequences of complete chloroplast genomes and many nuclear genes, our analyses yield two robust phylogenetic trees respectively. Chloroplast genome and nuclear data confidently resolved relationships of this genus into two major clades which largely supported current classification based on morphological evidence. However, conflicts between the chloroplast genome and low-copy nuclear phylogenies were observed in both the species level and clade level. Cyto-nuclear discordance in the phylogeny could be caused by frequent hybridization events and incomplete sorting lineage (ILS). In addition, our divergence-time analysis revealed an evolutionary radiation of the genus from late Miocene to date.

2.
Toxicol Appl Pharmacol ; 404: 115181, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758488

RESUMO

Exposure to ambient fine particulate matter (PM2.5) elicits various abnormalities in glycaemic control and thus correlates with type 2 diabetes. Intermittent fasting is an emerging treatment for type 2 diabetes. This study, therefore, tested whether intermittent fasting ameliorates PM2.5 exposure-induced abnormalities in glycaemic control. To this end, C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) for 16 weeks and concurrently subject to ad libitum feeding or intermittent fasting. The food intake assessment showed that CAP exposure transiently reduced food intake in ad libitum fed mice, but persistently reduced food intake in intermittently fasted mice. In contrast, CAP exposure persistently promoted mouse weight gain in ad libitum fed mice, while intermittent fasting blocked this CAP exposure-induced weight gain. The glucose homeostasis assessments revealed that CAP exposure elicited insulin resistance and glucose intolerance and meanwhile increased glucose-induced insulin secretion (GIIS). The insulin resistance and glucose intolerance, but not the increase in GIIS, induced by CAP exposure were blocked by intermittent fasting. Analysis of Akt phosphorylation, the indicator of local insulin signaling, showed that CAP exposure reduced insulin signaling in the liver and adipose tissues but not in the skeletal muscle. Intermittent fasting blocked CAP exposure-induced insulin resistance in the liver but not in the adipose tissues. The present study demonstrates that intermittent fasting ameliorates PM2.5 exposure-induced insulin resistance and glucose intolerance, strongly supporting that it may be used to prevent type 2 diabetes due to exposure to PM2.5.

3.
Clin Sci (Lond) ; 134(12): 1475-1489, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32538435

RESUMO

Sphingosine-1-phosphate (S1P) is a pleiotropic lysosphingolipid derived from the metabolism of plasma membrane lipids. The interaction between S1P and its ubiquitously expressed G-protein-coupled receptors (S1PR1-5) is crucial in many pathophysiological processes. Emerging evidence suggested a potential role for S1P receptors in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the present study, we investigated the effects of three different S1P receptors modulators (FTY720, SEW2871 and TY52156) in a recognized rat model of experimental autoimmune vasculitis (EAV). The effects of treatments were evaluated with clinico-pathological parameters including hematuria, proteinuria, crescent formation, pulmonary hemorrhage, etc. In vitro functional studies were performed in a Jurkat T-cell line following stimulations of serum from myeloperoxidase-AAV patients. We found that only the FTY720 treatment significantly alleviated hematuria and proteinuria, and diminished glomerular crescent formation, renal tubulointerstitial lesions and pulmonary hemorrhage in EAV. The attenuation was accompanied by less renal T-cell infiltration, up-regulated mRNA of S1PR1 and down-regulated IL-1ß in kidneys, but not altered circulating ANCA levels, suggesting that the therapeutic effects of FTY720 were B-cell independent. Further in vitro studies demonstrated that FTY720 incubation could significantly inhibit the proliferation, adhesion, and migration, and increase apoptosis of T cells. In conclusion, the S1P modulator FTY720 could attenuate EAV through the reduction and inhibition of T cells, which might become a novel treatment of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Cloridrato de Fingolimode/uso terapêutico , Peroxidase/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Anticorpos/imunologia , Apoptose , Feminino , Cloridrato de Fingolimode/farmacologia , Hematúria/complicações , Humanos , Células Jurkat , Rim/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteinúria/complicações , Ratos Endogâmicos WKY , Transdução de Sinais
4.
PhytoKeys ; 146: 61-69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440252

RESUMO

Eriobotrya laoshanica, a new species of Rosaceae from Yunnan, China, is described and illustrated. The new species is easily distinguished from the most similar species E. malipoensis K. C. Kuan by its longer petioles (2-5 vs. 0.5-1 cm); indumentum on the lower leaf surfaces (densely tomentose vs. glabrous); much fewer flowers (15- to 30-flowered vs. 50- to 100-flowered) on the panicle; larger flowers (2.5-3 vs. 1.5-2 cm in diameter); and non-angulated (vs. angulated) young fruits.

5.
J Autoimmun ; 107: 102372, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810856

RESUMO

The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQß1-Pro55, HLA-DPB1*17:01 or HLA-DPß1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRß1-Ala74, HLA-DQß1-Pro55 and HLA-DPß1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQß1 position 55 and HLA-DPß1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

6.
Mol Biol Rep ; 46(6): 6547-6556, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31583570

RESUMO

Rhodoleia Champion ex Hooker is one of the most primitive relict genera of Hamamelidaceae, a key family exploited to understand the origin and early evolution of flowering plants. Genomic simple sequence repeats (SSRs) were developed for R. championii to perform genetic diversity, phylogeographical structure or even systematic evolution studies of the genus. Among the 278,743 contigs (105,758,242 bps) de novo assembled from the low-coverage whole genome sequencing of R. championii, a total of 9106 SSRs were detected in 8370 contigs, and SSR primer pairs were successfully designed for 6677 SSRs. Among the 110 selected primer pairs, 41 were amplified successfully in the preliminary test of SSR screening. Further amplification of these 41 primer pairs across the 122 individuals collected from six populations of the three Rhodoleia species showed that 32 and 40 SSR markers can be amplified in Vietnam and Jinping populations of R. parvipetala, 41, 33, and 41 SSR markers in Boluo, Hongkong and Xinyi populations of R. championii, 25 SSR markers in Fugong population of R. forrestii, and 20 SSR markers demonstrated to be polymorphic across the three species. Genetic analysis for these 20 polymorphic SSRs showed that Allele number (A) ranged from four to 13 and polymorphic information content (PIC) ranged from 0.479 to 0.876 across the three species. At the population level, observed heterozygosity (HO) ranged from 0.000 to 1.000, and expected heterozygosity (HE) ranged from 0.091 to 0.851. In the present study, we provided the first whole-genome sequencing database for the species R. championii, identified ample SSR loci with designed primers, and revealed that 20 of the 110 selected SSRs were polymorphic across three Rhodoleia species. These provide valuable resources for future studies on genetic study, species delimitation, phylogeography, and conservation of this genus.


Assuntos
Repetições de Microssatélites , Árvores/classificação , Sequenciamento Completo do Genoma/métodos , DNA de Plantas/genética , Desequilíbrio de Ligação , Especificidade da Espécie , Árvores/genética
7.
Kidney Int ; 96(4): 1010-1019, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31471160

RESUMO

A genome-wide association study (GWAS) indicated that myeloperoxidase-ANCA associated vasculitis (AAV) is associated with HLA-DQ. However, susceptibility alleles in these loci have been under-investigated. Here we genotyped 258 Chinese patients with myeloperoxidase-AAV and 597 healthy control individuals at HLA DRB1, DQA1, DQB1 and DPB1, and extracted the encoded amino acid sequences from the IMGT/HLA database. The replication cohort included 97 cases and 107 controls. T cell epitopes of myeloperoxidase were predicted and docked to the HLA molecules. We found DQA1∗0302 (odds ratio 2.34 (95% confidence interval 1.75-3.14)) and DQB1∗0303 (odds ratio 1.89 (1.45-2.48)) were risk alleles for myeloperoxidase-AAV. They are in overt linkage disequilibrium (r2 0.69) and the haplotype DQA1∗0302-DQB1∗0303 presents a significant risk (haplotype score 6.39) as well. Aspartate160 on the DQ α chain (odds ratio 2.06 (1.60-2.67)), encoded by DQA1∗0302, and isoleucine185 on the DQ ß chain (odds ratio 1.73 (1.38-2.18)), encoded by DQB1∗0303, both located in the α2ß2 domains, conferred significant risk for myeloperoxidase-AAV. Homologous modeling showed that DQα∗160D may confer susceptibility to myeloperoxidase-AAV by altering dimerization of the HLA molecules. Thus, more attention should be paid to the roles of amino acids in the α2ß2 domains in addition to the α1ß1 binding groove of HLA class II molecules.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Peroxidase/imunologia , Adulto , Idoso , Alelos , Aminoácidos/genética , Aminoácidos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Estudo de Associação Genômica Ampla , Cadeias alfa de HLA-DQ/imunologia , Cadeias beta de HLA-DQ/imunologia , Humanos , Desequilíbrio de Ligação/imunologia , Masculino , Pessoa de Meia-Idade
8.
ACS Appl Mater Interfaces ; 11(39): 36278-36285, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490648

RESUMO

Carbon nanotube (CNT) buckypapers, or films, have the potential for wide applications because of their unique properties. Neat buckypapers or pristine CNT (PCNT) films have relatively large elongation but low strength and low modulus due to the weak interaction between CNTs. Chemical modifications of PCNT films can significantly strengthen the interaction between CNTs, resulting in high strength and high modulus but usually accompanied by low elongation. Here, we report the functionalization of pristine CNT films by thiol-ended hyperbranched polymers (THBP-n) via a thiol-ene click reaction that can introduce simultaneous improvements on the strength, modulus, and elongation to the PCNT film by 689, 812, and 32.4%, respectively. The high thiol content of THBP-n enables the formation of a network with a high degree of cross-linking between carbon nanotubes, which provides high-efficiency load transfer that increases the tensile strength and modulus of the resulting films and at the same time a compressible hyperbranched structure that allows for deformation and slip between CNTs and consequently improved elongation. The main factors affecting the mechanical performance of the functionalized CNT film are also investigated.

9.
Adv Exp Med Biol ; 1165: 423-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399977

RESUMO

Chronic kidney disease (CKD) is a public health problem worldwide, with increasing incidence and prevalence. The mechanisms underlying the progression to end-stage renal disease (ESRD) is not fully understood. The complement system was traditionally regarded as an important part of innate immunity required for host protection against infection and for maintaining host hemostasis. However, compelling evidence from both clinical and experimental studies has strongly incriminated complement activation as a pivotal pathogenic mediator of the development of multiple renal diseases and progressive replacement of functioning nephrons by fibrosis. Both anaphylatoxins, i.e., C3a and C5a, and membrane attack complex (MAC) contribute to the damage that occurs during chronic renal progression through various mechanisms including direct proinflammatory and fibrogenic activity, chemotactic effect, activation of the renal renin-angiotensin system, and enhancement of T-cell immunity. Evolving understanding of the mechanisms of complement-mediated renal injury has led to the emergence of complement-targeting therapeutics. A variety of specific antibodies and inhibitors targeting complement components have shown efficacy in reducing disease in animal models. Moreover, building on these advances, targeting complement has gained encouraging success in treating patients with renal diseases such as atypical hemolytic uremic syndrome (aHUS). Nevertheless, it still requires a great deal of effort to develop inhibitors that can be applied to treat more patients effectively in routine clinical practice.


Assuntos
Ativação do Complemento , Nefropatias/imunologia , Animais , Síndrome Hemolítico-Urêmica Atípica , Proteínas do Sistema Complemento , Fibrose , Humanos , Rim/patologia
10.
Am J Clin Pathol ; 152(4): 517-526, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31247063

RESUMO

OBJECTIVES: Our goal was to assess the expression of histone acetyltransferase binding to origin recognition complex 1 (HBO1) in gastric cancer and the effect on prognosis for the patients. METHODS: We used quantitative reverse transcription polymerase chain reaction, Western blot, and tissue microarray immunohistochemistry to investigate the expressions of HBO1 messenger RNA (mRNA) and protein in gastric cancer tissues. Online resources, including Oncomine and Kaplan-Meier Plotter, were used to further assess the correlation between HBO1 expression and the prognosis of the patients with gastric cancer. RESULTS: HBO1 mRNA and protein expressions in gastric cancer tissues were both significantly higher than those in normal tissues. The correlations between high HBO1 expression and differentiation, invasive depth (T), lymph node metastasis (N), distant metastasis (M), TNM staging, and serum carcinoembryonic antigen levels were positive. High HBO1 expression was negatively correlated with survival time in patients with gastric cancer. CONCLUSIONS: HBO1 might be a valuable biomarker to evaluate the prognosis of patients with gastric cancer.


Assuntos
Adenocarcinoma/patologia , Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Acetiltransferases/metabolismo , Neoplasias Gástricas/patologia , Estômago/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Feminino , Gastrite/genética , Gastrite/metabolismo , Gastrite/patologia , Histona Acetiltransferases/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
11.
Mol Immunol ; 112: 322-329, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31238287

RESUMO

OBJECTIVE: The morbidity and prevalence of type 2 diabetes mellitus (DM) are increasing in the elderly population. Interleukin 37 (IL-37) play important roles in anti-inflammatory and anti-bacteria immune responses, but its role in the development of type 2 DM in the elderly is unclear. Therefore, we investigated whether IL-37 is associated with type 2 DM in the elderly and the underlying mechanism. METHODS: Hospitalized patients (aged 65-95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively and compared with healthy subjects without glucose metabolism abnormalities. A diabetic mouse model was established by feeding ob/ob mice (C57BL/6) a high-fat, carbohydrate-free diet. Plasma glucose and insulin levels were determined by glucose oxidase assay and radioimmunoassay, respectively. The IL-37 expression level was determined by real-time PCR, western blot and ELISA (Enzyme-linked immunoassay). RESULTS: Statistic analysis showed that the IL-37 level was significantly associated with type 2 DM and insulin resistance in the elderly. The patients were then divided into insulin therapy sensitive and resistant group according to their response to insulin therapy. Data showed that the IL-37 was highly expressed in the insulin therapy sensitive group. And this was related to the less severe gut microbiota dysbiosis. In the mice model, overexpressing the IL-37 could suppress the gut microbiota dysbiosis and also the diabetes development. CONCLUSION: Thus our results showed that higher IL-37 was associated with increased insulin sensitive in elderly type 2 DM patients through suppressing the gut microbiota dysbiosis.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Interleucina-1/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Feminino , Células HEK293 , Humanos , Resistência à Insulina/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Appl Plant Sci ; 7(5): e01246, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31139512

RESUMO

Premise: Ixonanthes (Ixonanthaceae) consists of between three and 19 species, among which I. chinensis and I. khasiana are considered vulnerable. Here, 58 microsatellite markers were developed for further conservation of these two Ixonanthes species. Methods and Results: RNA transcripts of I. chinensis were sequenced and assembled into 19,545 unigenes, and 994 simple sequence repeat (SSR) loci were identified from 920 contigs. Based on these, 106 primer pairs were designed, 58 were successfully amplified, and 12 demonstrated polymorphism among five populations. The number of alleles per locus varied from three to 10, and the levels of observed and expected heterozygosity ranged from 0.000 to 1.000 and 0.000 to 0.844, respectively. Further assessment of the transferability of the 58 amplifiable primers reported 30 being successfully cross-amplified in I. icosandra and three in Erythroxylum sinense. Conclusions: These novel SSR markers will be useful for future genetic conservation studies on these Ixonanthes species.

13.
Environ Health Perspect ; 127(5): 57009, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31095431

RESUMO

BACKGROUND: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]). This central role, however, has not yet been systemically examined. OBJECTIVE: In the present study, we exploited a lung epithelial cell-specific inhibitor [Formula: see text] kinase 2 (IKK2) knockout mouse model to determine the role of pulmonary inflammation in the pathophysiology due to exposure to diesel exhaust particulate matter (DEP). METHODS: [Formula: see text] (lung epithelial cell-specific IKK2 knockout, KO) and [Formula: see text] (wild-type, tgWT) mice were intratracheally instilled with either vehicle or DEP for 4 months, and their inflammatory response and glucose homeostasis were then assessed. RESULTS: In comparison with tgWT mice, lung epithelial cell-specific IKK2-deficient mice had fewer DEP exposure-induced bronchoalveolar lavage fluid immune cells and proinflammatory cytokines as well as fewer DEP exposure-induced circulating proinflammatory cytokines. Glucose and insulin tolerance tests revealed that lung epithelial cell-specific IKK2 deficiency resulted in markedly less DEP exposure-induced insulin resistance and greater glucose tolerance. Akt phosphorylation analyses of insulin-responsive tissues showed that DEP exposure primarily targeted hepatic insulin sensitivity. Lung epithelial cell-specific IKK2-deficient mice had significantly lower hepatic insulin resistance than tgWT mice had. Furthermore, this difference in insulin resistance was accompanied by consistent differences in hepatic insulin receptor substrate 1 serine phosphorylation and inflammatory marker expression. DISCUSSION: Our findings suggest that in a tissue-specific knockout mouse model, an IKK2-dependent pulmonary inflammatory response was essential for the development of abnormal glucose homeostasis due to exposure to DEP. https://doi.org/10.1289/EHP4591.


Assuntos
Poluentes Atmosféricos/toxicidade , Glucose/fisiologia , Homeostase , Quinase I-kappa B/deficiência , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Animais , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos
14.
Mol Biol Rep ; 46(3): 3381-3386, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989557

RESUMO

Hamamelidaceae (Saxifragales, previously Rosales) comprises approximately six subfamily, 30 genera and 140 species, most of which are Tertiary relicts. Exbucklandia is the only genus of the subfamily Exbucklandioideae, Hamelidaceae, containing only 2-4 species. Of them, the species E. longipetala H. T. Chang is endemic to China and listed as endangered in The Biodiversity Red List of China: Higher Plant, yet some taxonomists put forward that E. longipetala should be merged into E. tonkinensis (Lecomte) H. T. Chang. Currently, there was nearly no phylogeographic studies on this genus possibly due to the deficiency of efficient molecular markers. In this study, we sequenced the genome of E. tonkinensis based on high throughput sequencing technology, and obtained approximately 6 G raw data, which was further de novo assembled into 303,481 contigs. Based on them, 15,326 SSRs were identified from 13,596 contigs, and primers were successfully designed for 10,660 SSRs. A total of 139 paired primers were synthesized, 106 of them were successfully amplified in six Exbucklandia individuals with expected PCR product size, and 24 demonstrated to be polymorphic among three Exbucklandia populations. Accordingly, the expected and observed heterozygosity were between 0.097-0.717 and 0.098-0.583. Based on these efforts, future researches on genetic diversity and population structure of Exbucklandia can be performed to understand its phylogenetic origins and phylogeographic pattern.


Assuntos
Hamamelidaceae/genética , Repetições de Microssatélites/genética , Saxifragales/genética , China , Marcadores Genéticos/genética , Genética Populacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Filogenia , Folhas de Planta/genética , Polimorfismo Genético/genética , Análise de Sequência de DNA/métodos
15.
Hepatology ; 70(1): 294-307, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30854688

RESUMO

Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRß1-Asn77/Arg74, DRß1-Ser37, and DPß1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.


Assuntos
Anticorpos Antinucleares/genética , Antígenos Nucleares/imunologia , Autoantígenos/imunologia , Cirrose Hepática Biliar/genética , Idoso , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-Idade
16.
Mol Med Rep ; 19(5): 3633-3641, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864725

RESUMO

Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75 min of superior mesenteric artery occlusion, followed by 3 h of reperfusion. GRb1 (15 mg/kg) was administered intraperitoneally 1 h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3­kinase (PI3K) inhibitor, 0.6 mg/kg]. The degree of intestinal injury and oxidative stress­induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D­lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8­iso­prostaglandin F2α (8­iso­PGF2α). The protein expression levels of p85, phosphorylated (p)­p85, protein kinase B (Akt), p­Akt and nuclear factor erythroid 2­related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor­α (TNF­α), interleukin (IL)­1ß and IL­6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF­α, IL­1ß, IL­6, MDA and 8­iso­PGF2α in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway.


Assuntos
Ginsenosídeos/farmacologia , Inflamação/etiologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Malondialdeído/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
17.
Sci Data ; 6: 180308, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30747911

RESUMO

We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.


Assuntos
Cognição , Emoções , Adulto , Fatores Etários , Idoso , Eletroencefalografia , Feminino , Alemanha , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Psicofisiologia/métodos , Adulto Jovem
18.
Ecol Evol ; 8(22): 10938-10951, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30519418

RESUMO

Fokienia hodginsii is a Tertiary relict conifer of the monotypic genus Fokienia (Cupressaceae s.l.). Currently, the species is distributed in southern China, northern Vietnam, and northern Laos and listed as a "near threatened" species by the IUCN. In this study, a total of 427 individuals of F. hodginsii were sampled from China and Vietnam to characterize its genetic diversity and population differentiation. Based on the profiles of 12 simple sequence repeat (SSR) markers, we observed a high level of genetic diversity in F. hodginsii at the species level (H e =0.635), albeit slightly lower than that of its sister species Chamaecyparis obtusa. Signals of bottleneck events were detected in the populations GXDMS, GXHJ, V-PXB, and V-HB, probably due to Pleistocene glaciations or overexploitation in recent years. Pronounced genetic differentiation (F st   = 0.157) was found in this species. The inbreeding index (F is  = 0.176 ± 0.024) indicated that F. hodginsii has a mixed mating system. Significant correlation was found between the pairwise genetic differentiation and geographic distance (r = 0.882, p = 0.01), suggesting that genetic differentiation among the populations follows the model of isolation by distance (IBD). STRUCTURE analysis and principal coordinate analysis revealed that these populations were divided into four groups: the western China group located mainly in the Yunnan-Guizhou Plateau, the central China group located mostly in the Luoxiao Mountains and Nanling Mountains, the eastern China group located in the Wuyi Mountains and the Vietnam group containing two populations in Vietnam. The different terrains and elevations of populations may be the most likely factors leading to the differentiation between the western China group and the central China group, while the geographic isolation caused by the lack of appropriate habitats may greatly contribute to the differentiation between the central China group and the eastern China group. Based on the results, some conservation suggestions for this species are provided, such as establishing seed orchards and multiple nature reserves.

19.
Appl Plant Sci ; 6(10): e01189, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30386715

RESUMO

Premise of the Study: Hamamelis mollis (Hamamelidaceae) is a Tertiary relict species endemic to southern China. Polymorphic microsatellite markers were developed to reveal the genetic diversity of this species. Methods and Results: The genome of H. mollis was sequenced and de novo assembled into 642,351 contigs. A total of 72,097 paired primers were successfully designed from 80,282 simple sequence repeat (SSR) markers identified in 63,419 contigs. PCR amplification showed that 96 of the 136 synthesized primers could be successfully amplified, and 22 demonstrated polymorphism. The mean number of alleles, levels of observed heterozygosity, and levels of expected heterozygosity were 4.602 ± 0.140, 0.632 ± 0.020, and 0.696 ± 0.010, respectively. The majority of the 96 primer pairs could be amplified in at least one other Hamamelidaceae species, including Distylium myricoides (60), Loropetalum chinense (39), Exbucklandia populnea (24), and E. tonkinensis (24). Conclusions: These microsatellite loci provide abundant genomic SSR markers to evaluate genetic diversity of this woody ornamental plant.

20.
J Mol Endocrinol ; 61(4): 153-161, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30021757

RESUMO

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1 deficient mice (TNFR1-/-), TNFα/LTα/LTß triple deficient mice (TNF/LT∆3), and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test, and oral glucose tolerance test. The present results showed that TNFR1-/- and TNF/LT∆3 mice versus their controls had comparable body weight, tolerance to intraperitoneal glucose, and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1-/- and TNF/LT∆3 mice versus their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Peptídeo 1 Semelhante ao Glucagon/genética , Insulina/genética , Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/genética
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