Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 941
Filtrar
2.
Plant Dis ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609206

RESUMO

Chinese catalpa, Catalpa bungei C.A. Mey is native to China and has been widely cultivated as an important tree species for timber and ornamental purposes (Tao et al. 2019). The properties and high durability of the wood can resist the damage caused by microorganisms and insects (Xiao Y et al. 2019). In September 2020, stem cankers were observed in 5-year-old and 3-year-old C. bungei in a pilot experiment field covering 16-hectare area in Shuyang city (Jiangsu province, China) and in a nursery in Binhai city (Jiangsu Province, China), respectively. The disease incidence in both locations was about 1% to 3%. The typical disease symptoms include small to large, dark-brown and irregular-sunken canker around and along the stem under 2 meters from the stem base. The phloem and xylem of the symptomatic stem were dark brown and the xylem had larger necrosis than the phloem. The cross section of the diseased stem was partially died. The symptomatic stem were collected in both locations for pathogen isolation. In total, seven purified isolates from the diseased samples were obtained using potato dextrose agar (PDA) following standard isolation protocol (Huang et al. 2019). In order to determine the pathogenicity, 3-year-old Chinese catalpa seedlings were artificially inoculated with each of the seven isolates in April 2021. After removing the bark of the stem by a sterilized punch (diameter 6mm), an agar plug (diameter 6mm) pre-colonized by the isolate was inoculated to the stem and the inoculation point was sealed with parafilm. The agar plug without pre-colonization was used as control. Six tree seedlings were inoculated for each isolate. Ten days after inoculation, only the treatment with isolate QS.1 showed obvious discoloration around the inoculation point. One month after inoculation, the canker around the inoculation point was formed (3.4 cm ± 1.0 cm) and spread to the xylem, similar to the symptoms observed in the field. Isolate QS.1 was re-isolated successfully from the inoculated stem based on morphological characters, confirming the Koch's postulates and QS.1 as the causal pathogen. The isolate QS.1 formed white colonies with abundant aerial mycelia on V8 juice agar and produced a large amount of persistent and papillary ovoid sporangia with size of 22 ~ 45µm (average 31µm) × 18 ~ 39µm (average 23µm) in 10% aqueous solution of V8. The spore was spherical with thick-wall and diameter of 24 ± 3.9µm. The morphology of QS.1 is similar to that of Phytophthora nicotianae. The genomic DNA of representative isolate QS.1 was extracted from mycelium by a modified CTAB method (Murray et al. 1980). The rDNA internal transcribed spacer (ITS) region, ß-tubulin and EF1-α genes were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), BTub_F1/TUBUR1 (L. et al. 2004) and EF1A_for/EF1A_rev (Blair et al. 2008), respectively. The BLAST results of these sequences (Accession No. MZ646302, MZ672116, and MZ675589, respectively) showed 99%, 100% and 100% identity with sequences of P. nicotianae (Accession No. KJ494902, KY205750, and MH359041), respectively. Based on the morphological characteristics and DNA analysis, isolate QS.1 was identified as P. nicotianae. To our best knowledge, this is the first report of P. nicotianae causing stem canker on Chinese Catalpa. This disease may pose potential threat on Catalpa due to the increase in Catalpa planting for economic and ecological purposes in China.

4.
Lab Med ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34508270

RESUMO

OBJECTIVES: To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. METHODS: The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. RESULTS: Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003). CONCLUSIONS: The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.

5.
Am J Gastroenterol ; 116(9): 1929-1937, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465695

RESUMO

INTRODUCTION: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS: Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 µg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). DISCUSSION: Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.


Assuntos
Dor Abdominal/tratamento farmacológico , Constipação Intestinal/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Peptídeos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
6.
7.
Analyst ; 146(20): 6170-6177, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34522939

RESUMO

Triphenyltin chloride (TPhT) is an organotin compound that causes intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT. In this study, a novel SERS substrate was prepared by sputtering an ultra-thin Au layer on a honeycomb-like silver nanoarray fabricated via the nanosphere lithography method. The ultra-thin Au layer was formed by sputtering the intermittent Au nanoparticles on the silver nanoarray, resulting in bimetallic coupling with dramatically increased hotspots and extremely high SERS enhancement with an analytical enhancement factor (AEF) of 6.08 × 109 using Rhodamine 6G (R6G) as the probe molecule. Based on density functional theory (DFT) simulations, the Raman characteristic peaks of TPhT at 999 cm-1 and 655 cm-1 were selected for TPhT detection. The AEF of the SERS substrate HC5-AgAu was calculated to be 3.38 × 106 with the detection concentration of TPhT down to 10-10 M. The as-prepared honeycomb-like silver-gold bimetallic SERS substrate demonstrated great stability and sensitivity for TPhT detection, which might also be applied in monitoring many other environmental pollutants.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Compostos Orgânicos de Estanho , Prata , Análise Espectral Raman
8.
J Invertebr Pathol ; 184: 107653, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34371089

RESUMO

Enterocytozoon hepatopenaei (EHP), a recently reported pathogen in the penaeid shrimp, is spreading widely and seriously threatening Penaeus (Litopenaeus) vannamei aquaculture. This study aimed to develop a new and more sensitive polymerase chain reaction (PCR) method for the effective detection of EHP. An EHP PCR assay with a pair of primers specifically amplifying a 358 bp EHP DNA fragment was developed, which was demonstrated to be capable of detecting as low as 2 × 101 copies of EHP and is specific for EHP without cross reaction with DNA samples prepared from five common shrimp pathogens, including white spot syndrome virus (WSSV), infectious hypodermal and haematopoietic virus (IHHNV), hepatopancreatic parvovirus (HPV), infectious myonecrosis virus (IMNV), and yellow head virus (YHV). This new assay is more specific and more sensitive than the previously published EHP PCR methods. With the PCR assay developed in this study, we investigated the prevalence of EHP in four areas of Shandong, China by testing a total of 639 shrimp samples collected from Yantai, Binzhou, Dongying, and Weifang. The results showed that the EHP positive rate reached 51.2%, indicating that EHP is prevalent in shrimp culture in China.

9.
Clin Pharmacol Ther ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383294

RESUMO

Immunogenicity, the potential to elicit an antidrug immune response, is a critical concern in developing biological products, but its consequences are difficult to predict with animal studies. The aims of the present study are to investigate the evolution of immunogenicity information in labeling and to identify attributes associated with immunogenicity labeling updates. Biologics License Applications (BLAs) approved by the Center for Drug Evaluation and Research, US Food and Drug Administration between 2008 and 2017 were studied. A majority of BLAs described the incidence/prevalence of antidrug antibodies (ADAs) (94.9%) and neutralizing antibodies (NAbs) (68.4%) in their original labeling documents. However, less than one third of the BLAs mentioned the impact of ADAs/NAbs in the original (20.3%) and most recent (29.1%) labeling documents. BLAs with a priority review status (57.4% vs. 33.3%), orphan designation (61.5% vs. 34.2%), or a mention of ADA impact in the latest label (69.6% vs. 38.9%) had higher percentages of applications with postmarketing requirements (PMRs) directly related to immunogenicity concerns in comparison with applications without those characteristics. Among the BLAs with updated immunogenicity information, the mean time to the first update was 1,077 days, while that for BLAs with accelerated approval was shorter (709.1 ± 492.2 days vs. 1173.8 ± 661.8 days). The results suggest that there is a substantial amount of critical information lacking in the original labeling documents and an overdependence on PMRs for more evidence. Additional efforts should be made to investigate the impact of ADAs to provide timely information for improved patient care.

10.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3298-3302, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396748

RESUMO

Through literature analysis of Pheretima and its origin-related earthworm,this study summarized the progress on Pheretima in textual criticism of origin,origin identification,effective components,detection of harmful components,and pharmacological effects,which can lay a basis for further research on Pheretima. Through literature research,the authors found that Pheretima was first recorded in Secret Formulary for Traumatology and Fracture Taught by Immortal written by LIN Daoren in Tang Dynasty rather than the Taiping Holy Prescriptions for Universal Relief in Song Dynasty. The latest techniques for origin identification include microscopic trait identification,DNA barcoding,and HPLC. The main effective components of Pheretima are proteins,polypeptides,enzymes,nucleotides,amino acids,and trace elements. According to recent studies,Pheretima has anti-pulmonary and anti-renal interstitial fibrosis,respiratory syncytial virus-inhibiting,human hypertrophic scar fibroblast proliferation-suppressing,and mouse embryonic fibroblast proliferation-promoting effects. Moreover,Pheretima can prevent colitis-induced colon cancer by inhibiting the activation of COX-2/PGE2/ß-catenin signaling pathway. METHODS:: for detecting the harmful components and their residues( organic pollutant polychlorinated biphenyl,heavy metals) and bacteria in Pheretima,have been established. Pheretima,mainly derived from wild earthworms,has remarkable clinical efficacy. However,the wild resource is in short supply and artificial culture is expected to be a promising solution.


Assuntos
Oligoquetos , Animais , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2 , DNA , Fibroblastos , Camundongos
11.
Aging (Albany NY) ; 13(16): 20534-20551, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432650

RESUMO

OBJECTIVE: The NOD-like receptor protein 3 (NOD-like receptor protein 3, NLRP3) inflammasome is associated with many physiological processes related to aging. We investigated whether NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging dissected the underlying mechanism. METHODS: H9c2 cells were treated with different concentrations of D-galactose (D-gal, 0, 2, 10 and 50 g/L) for 24 hours. The cytochemical staining, flow cytometry and fluorescence microscope analysis were employed to detect the ß-galactosidase (ß-gal) activity. Western blot analysis was used to detect the age-associated proteins (P53, P21) and NLRP3 inflammasome proteins [NLRP3, apoptosis-associated speck-like protein (ASC)]. Confocal fluorescent images were applied to capture the colocalization of NLRP3 and caspase-1. Intracellular reactive oxygen species (ROS) was measured using 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) by flow cytometry and visualized using a fluorescence microscope. The IL-1ß, IL-18 and lactate dehydrogenase (LDH) release were also detected. RESULTS: D-gal induced-H9c2 cells caused cardiocytes' aging changes (ß-gal staining, CellEvent™ Senescence Green staining, P53, P21) in a concentration-dependent manner. NLRP3 inflammasomes were activated, IL-1ß, IL-18 and LDH release and ROS generation were increased in the cardiocytes aging progress. When MCC950 inhibited NLRP3 inflammasomes, it attenuated the cardiocytes aging, yet the ROS generation was similar. Inhibition of ROS by NAC attenuated cardiocytes aging and inhibited the NLRP3 inflammasome activation at the same time. NLRP3 inflammasome activation by nigericin-induced cardiocytes cells aging progress. CONCLUSIONS: NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging, and ROS generation may serve as a potential mechanism by which NLRP3 inflammasome is activated.

12.
Am J Gastroenterol ; 116(10): 2148-2149, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34404085
13.
Int Immunopharmacol ; 99: 107972, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34298401

RESUMO

We sought to assess the protective effect of different doses of Fingolimod (FTY720) in a rat model of acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) and explored the underlying mechanisms. The ALI model was established in rats and different doses of FTY720 (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, or 2 mg/kg) were injected intraperitoneally. Lung computed tomography and blood gas analyses were performed at 6 h, 24 h, and 48 h after intraperitoneal injection, and the lung tissues were extracted to prepare paraffin sections for histopathological examination. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) were detected by ELISA, and the expressions of inflammatory pathway proteins in each group were measured by Western blot analysis. A single intraperitoneal injection of FTY720 inhibited LPS-induced NF-κB activation, reduced the level of inflammatory cytokines, and decreased the infiltration of inflammatory cells. Moreover, it alleviated lung tissue injury, as shown by marked attenuation of pulmonary oedema and improved arterial partial pressure of oxygen (PaO2) and the general condition of ALI rats. In conclusion, our results demonstrate the protective effect of FTY720 against LPS-induced ALI. The underlying mechanism of the protective effect may involve inhibition of LPS-induced activation of NF-κB and regulation of the inflammatory pathway to alleviate barrier dysfunction of alveolar capillaries.

14.
Gastroenterol Clin North Am ; 50(3): 505-522, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34304785

RESUMO

The pathogenesis of irritable bowel syndrome is multifactorial and complex. Our understanding of its pathophysiology has evolved, but remains incompletely understood. Symptoms result from a dysregulation of brain-gut interactions. Evidence has identified alterations in central and peripheral (gut) mechanisms in irritable bowel syndrome and the bidirectional communication between the brain and the gut. Pertinent mechanisms include disturbed gut motility, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing. This review addresses factors that increase the risk of irritable bowel syndrome and the central and peripheral mechanisms thought to underlie its symptoms.

15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(8): 716-721, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34236031

RESUMO

Objective To explore the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis, migration and invasion of osteosarcoma cell line U2OS and its possible molecular mechanism. Methods Human osteosarcoma cell line U2OS was cultured and treated with (0, 200, 400, 600, 800, 1000) µg/mL PNS. The proliferation of U2OS was detected by CCK-8 method. Annexin V-FITC/PI double labeling combined with flow cytometry was used to analyze cell apoptosis. Clone formation assay was used to detect the clone formation ability of the cells. TranswellTM invasion assay was performed to detect cell invasion. TranswellTM migration assay and wound-healing assay were used to determine cell migration. Western blotting was used to detect the expression of Notch1 and downstream protein Hes1 in U2OS cells. Results Compared with the control group, PNS could inhibit the proliferation of U2OS cells and the formation of clonal plaques, increase cell apoptosis rate, weaken the ability of migration and invasion and decrease the expression levels of Notch1 and Hes1 in the cells in a dose-dependent manner. Conclusion PNS can significantly inhibit the proliferation, migration and invasion and promote cell apoptosis of U2OS cells by blocking Notch1 signaling pathway.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Panax notoginseng , Saponinas , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Osteossarcoma/tratamento farmacológico , Receptor Notch1/genética , Saponinas/farmacologia
16.
Cell Rep ; 36(4): 109420, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320345

RESUMO

Dysregulated glycine metabolism is emerging as a common denominator in cardiometabolic diseases, but its contribution to atherosclerosis remains unclear. In this study, we demonstrate impaired glycine-oxalate metabolism through alanine-glyoxylate aminotransferase (AGXT) in atherosclerosis. As found in patients with atherosclerosis, the glycine/oxalate ratio is decreased in atherosclerotic mice concomitant with suppression of AGXT. Agxt deletion in apolipoprotein E-deficient (Apoe-/-) mice decreases the glycine/oxalate ratio and increases atherosclerosis with induction of hepatic pro-atherogenic pathways, predominantly cytokine/chemokine signaling and dysregulated redox homeostasis. Consistently, circulating and aortic C-C motif chemokine ligand 5 (CCL5) and superoxide in lesional macrophages are increased. Similar findings are observed following dietary oxalate overload in Apoe-/- mice. In macrophages, oxalate induces mitochondrial dysfunction and superoxide accumulation, leading to increased CCL5. Conversely, AGXT overexpression in Apoe-/- mice increases the glycine/oxalate ratio and decreases aortic superoxide, CCL5, and atherosclerosis. Our findings uncover dysregulated oxalate metabolism via suppressed AGXT as a driver and therapeutic target in atherosclerosis.

17.
Science ; 373(6550): 99-103, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210884

RESUMO

Silicon photonics enables wafer-scale integration of optical functionalities on chip. Silicon-based laser frequency combs can provide integrated sources of mutually coherent laser lines for terabit-per-second transceivers, parallel coherent light detection and ranging, or photonics-assisted signal processing. We report heterogeneously integrated laser soliton microcombs combining both indium phospide/silicon (InP/Si) semiconductor lasers and ultralow-loss silicon nitride (Si3N4) microresonators on a monolithic silicon substrate. Thousands of devices can be produced from a single wafer by using complementary metal-oxide-semiconductor-compatible techniques. With on-chip electrical control of the laser-microresonator relative optical phase, these devices can output single-soliton microcombs with a 100-gigahertz repetition rate. Furthermore, we observe laser frequency noise reduction due to self-injection locking of the InP/Si laser to the Si3N4 microresonator. Our approach provides a route for large-volume, low-cost manufacturing of narrow-linewidth, chip-based frequency combs for next-generation high-capacity transceivers, data centers, space and mobile platforms.

18.
Gastroenterology ; 161(4): 1092-1098.e3, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34331916
19.
Bioengineered ; 12(1): 3711-3725, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34269159

RESUMO

Rectal cancer is a life­threatening disease worldwide. Chemotherapy resistance is common in rectal adenocarcinoma patients and has unfavorable survival outcomes; however, its related molecular mechanisms remain unknown. To identify genes related to the initiation and progression of rectal adenocarcinoma, three datasets were obtained from the Gene Expression Omnibus database. In total, differentially expressed genes were analyzed from 294 tumor and 277 para-carcinoma samples from patients with rectal cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions were investigated. Cytoscape software and MicroRNA Enrichment Turned Network were applied to construct a protein-protein interaction network of the dependent hub genes and related microRNAs. The Oncomine database was used to identify hub genes. Additionally, Gene Expression Profiling Interactive Analysis was applied to determine the RNA expression level. Tumor immune infiltration was assessed using the Tumor Immune Estimation Resource database. The expression profiles of hub genes between stages, and their prognostic value, were also evaluated. During this study, data from The Cancer Genome Atlas were utilized. In rectal adenocarcinoma, four hub genes including CXCL1, CXCL2, CXCL3, and GNG4 were highly expressed at the gene and RNA levels. The expression of CXCL1, CXCL2, and CXCL3 was regulated by has-miR-1-3p and had a strong positive correlation with macrophage and neutrophil. CXCL2 and CXCL3 were differentially expressed at different tumor stages. High expression levels of CXCL1 and CXCL3 predicted poor survival. In conclusion, the CXCL1 and CXCL3 genes may have potential for prognosis and molecular targeted therapy of rectal adenocarcinoma.

20.
Am J Hum Genet ; 108(9): 1578-1589, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34265237

RESUMO

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown. A previous study implicated common variants in FBN1 with TAA disease risk. Here, we report a genome-wide scan of 1,351 TAA-affected individuals and 18,295 control individuals from the Cardiovascular Health Improvement Project and Michigan Genomics Initiative at the University of Michigan. We identified a genome-wide significant association with TAA for variants within the third intron of TCF7L2 following replication with meta-analysis of four additional independent cohorts. Common variants in this locus are the strongest known genetic risk factor for type 2 diabetes. Although evidence indicates the presence of different causal variants for TAA and type 2 diabetes at this locus, we observed an opposite direction of effect. The genetic association for TAA colocalizes with an aortic eQTL of TCF7L2, suggesting a functional relationship. These analyses predict an association of higher expression of TCF7L2 with TAA disease risk. In vitro, we show that upregulation of TCF7L2 is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease.


Assuntos
Aneurisma da Aorta Torácica/genética , Diabetes Mellitus Tipo 2/genética , Células Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Locos de Características Quantitativas , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Aorta/metabolismo , Aorta/patologia , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/patologia , Estudos de Casos e Controles , Caspase 3/genética , Caspase 3/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Células Endoteliais/patologia , Regulação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Íntrons , Michigan , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...