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The predatory gall midge, Aphidoletes aphidimyza (Rondani), and tobacco aphid cocoon wasp, Aphidius gifuensis Ashmead, are important natural enemies of Myzus persicae (Sulzer) (Hemiptera: Aphididae). Predation by A. aphidimyza and A. gifuensis can regulate M. persicae; however, how interspecific interference competition affects their foraging efficiency is unknown. Here, we investigated the consumption and parasitization abilities of A. aphidimyza 3rd instar larva and A. gifuensis adults under various conditions. Consumption of parasitized aphids by A. aphidimyza 3rd instar larvae was significantly lower than that of nonparasitized controls, with a substantial increase in handling time. The presence of A. gifuensis adults did not significantly affect the predation capacity of A. aphidimyza larvae. Relative to controls, A. aphidimyza larvae predation trace (PT) and imago activity significantly decreased A. gifuensis parasitism rates at different aphid densities. Further, A. aphidimyza larvae PT increased the A. gifuensis handling time of M. persicae, whereas the presence of A. aphidimyza adults had the opposite effect. Coexistence with heterospecific natural enemies reduced the parasitic capacity of A. gifuensis, whereas A. aphidimyza larvae predation capability was influenced to a lesser extent. Our results demonstrate that intraguild interactions strongly influence the predatory and parasitic efficacy of A. aphidimyza and A. gifuensis, although the effect on A. gifuensis was more pronounced. For effective biological control of M. persicae using A. aphidimyza and A. gifuensis, we recommend releasing A. aphidimyza first to mitigate intraguild predation and enhance the overall success of the pest control program.
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BACKGROUND: The effects of thoracic endovascular aneurysm repair (TEVAR) with additional distal bare metal stents (BMSs) in patients with subacute complicated type B aortic dissection (cTBAD) are unclear and are investigated in this retrospective study. METHODS: The medical records of 67 patients who received TEVAR due to subacute cTBAD were reviewed. Areas of true lumen (TL) and false lumen at 5 levels-- pulmonary artery (PA), diaphragm, renal artery (RA), middle of the infrarenal aorta, and aortic bifurcation-were measured using computed tomography before and 3, 6, and 12 months after surgery. The TL ratio (TL area/total aortic area) and total aortic area at each time point were compared between the TEVAR+BMS (n=37) and TEVAR-only (n=30) groups. The effects of BMS use and time were evaluated using generalized estimating equations and generalized linear regression models. RESULTS: Baseline characteristics, remodeling types, and clinical outcomes did not differ significantly between the 2 groups. Postoperative TL ratios at the diaphragm and RA were significantly higher in the TEVAR+BMS group than in the TEVAR-only group (p < 0.05). BMS use and time had significant interaction effects at the PA, diaphragm, and RA (all p < 0.05), but effects on total aortic area were not significant at any of the 5 parts. TL ratios at the diaphragm and RA exhibtied greater improvement in the TEVAR+BMS group than in the TEVAR-only group at postoperative months 6 and 12 (all p < 0.001). Aortic diameters at all 5 parts were significantly smaller in the TEVAR+BMS group than in the TEVAR-only group (all p < 0.05). CONCLUSION: In patients with subacute cTBAD, TEVAR with BMS implantation effectively expands the TL from the thoracic aorta to the RA but neither enhances aortic remodeling nor elicits any change in total aortic area in whole dissected aorta relative to TEVAR only.
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BACKGROUND: Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7 (autophagy related 7)-dependent mechanism serves as an essential mechanism to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9 (Ras-related protein Rab-9A)-dependent alternative mitophagy takes over the role during the chronic phase. Although it has been postulated that DRP1 (dynamin-related protein 1)-mediated mitochondrial fission and consequent separation of the damaged portions of mitochondria are essential for mitophagy, the involvement of DRP1 in mitophagy remains controversial. We investigated whether endogenous DRP1 is essential in mediating the 2 forms of mitophagy during high-fat diet (HFD)-induced obesity cardiomyopathy and, if so, what the underlying mechanisms are. METHODS: Mice were fed either a normal diet or an HFD (60 kcal %fat). Mitophagy was evaluated using cardiac-specific Mito-Keima mice. The role of DRP1 was evaluated using tamoxifen-inducible cardiac-specific Drp1knockout (Drp1 MCM) mice. RESULTS: Mitophagy was increased after 3 weeks of HFD consumption. The induction of mitophagy by HFD consumption was completely abolished in Drp1 MCM mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. The increase in LC3 (microtubule-associated protein 1 light chain 3)-dependent general autophagy and colocalization between LC3 and mitochondrial proteins was abolished in Drp1 MCM mice. Activation of alternative mitophagy was also completely abolished in Drp1 MCM mice during the chronic phase of HFD consumption. DRP1 was phosphorylated at Ser616, localized at the mitochondria-associated membranes, and associated with Rab9 and Fis1 (fission protein 1) only during the chronic, but not acute, phase of HFD consumption. CONCLUSIONS: DRP1 is an essential factor in mitochondrial quality control during obesity cardiomyopathy that controls multiple forms of mitophagy. Although DRP1 regulates conventional mitophagy through a mitochondria-associated membrane-independent mechanism during the acute phase, it acts as a component of the mitophagy machinery at the mitochondria-associated membranes in alternative mitophagy during the chronic phase of HFD consumption.
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Cardiomiopatias , Mitofagia , Animais , Camundongos , Autofagia/fisiologia , Cardiomiopatias/genética , Dinaminas/genética , Dinaminas/metabolismo , Coração , Dinâmica Mitocondrial , Mitofagia/fisiologia , Obesidade/genéticaRESUMO
BACKGROUND: Persistent false lumen (FL) perfusion with aneurysmal formation is common after thoracic endovascular aortic repair (TEVAR) for typical extended aortic dissection and is associated with poor outcomes. Endovascular FL embolization (FLE) has recently been tried for treatment of postdissection aortic aneurysm (PDAA). However, most reports address thoracic rather than abdominal FLE. In this study, we present the results of abdominal FLE in patients with residual patent abdominal FL following stent-graft repair for aortic dissection. METHODS: Between 2015 and 2019, 24 patients (mean age: 56.7 ± 11.8 years, range: 40-84 years, 18 male) received endovascular abdominal FLE using vascular plugs, coils, or candy plugs as the main surgery (5 patients) or auxiliary procedure (19 patients) after earlier stent-graft repair for aortic dissection (Type A: 9, Type B: 15). The medical records were reviewed and aortic remodeling was examined comparing the preembolization computed tomography (CT) and the most recent CT before reintervention. RESULTS: Technical success was achieved without any intraoperative complications, early morbidity, or mortality. Median follow-up was 34.4 months (range: 12-71). Regarding thoracic FL, 15 patients exhibited complete thrombosis before the procedure and did not change status thereafter except for 1 patient with distal stent-graft-induced new entry. In the other 9 patients, 6 exhibited increased thrombosis. With regard to the abdominal aorta, increased FL thrombosis only occurred in 8 patients with 3 (12.5%) achieving complete thrombosis. The maximal thoracic aortic diameter did not change (1.4 ± 5.6 mm) statistically, but the abdominal diameter increased significantly (4.3 ± 3.7 mm, p < 0.005). CONCLUSION: From our results, abdominal FLE is a safe procedure. However, covering all the re-entry tears is complex and the possibility of complete FL thrombosis is low. The abdominal aortic diameter appears to become enlarged in these patients. Continuous follow-up is necessary after FLE.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Trombose , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Aneurisma da Aorta Torácica/cirurgia , Resultado do Tratamento , Dissecção Aórtica/cirurgia , Stents , Trombose/cirurgia , Estudos RetrospectivosRESUMO
BCL-2-like protein 1 (BCL2L1) is a key component of cell survival and death mechanisms. Its dysregulation and altered ratio of splicing variants associate with pathologies. However, isoform-specific loss-of-function analysis of BCL2L1 remains unexplored. Here we show the functional impact of genetically inhibiting Bcl-x short-isoform (Bcl-xS) in vivo. Bcl-xS is expressed in most tissues with predominant expression in the spleen and blood cells in mice. Bcl-xS knockout (KO) mice show no overt abnormality until 3 months of age. Thereafter, KO mice develop cardiac hypertrophy with contractile dysfunction and splenomegaly by 6 months. Cardiac fibrosis significantly increases in KO, but the frequency of apoptosis is indistinguishable despite cardiomyopathy. The Akt/mTOR and JNK/cJun signaling are upregulated in male KO heart, and the JNK/cJun is activated with increased Bax expression in KO spleen. These results suggest that Bcl-xS may be dispensable for development but is essential for maintaining the homeostasis of multiple organs.
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Modification of cysteine residues by oxidative and nitrosative stress affects structure and function of proteins, thereby contributing to the pathogenesis of cardiovascular disease. Although the major function of thioredoxin 1 (Trx1) is to reduce disulfide bonds, it can also act as either a denitrosylase or transnitrosylase in a context-dependent manner. Here we show that Trx1 transnitrosylates Atg7, an E1-like enzyme, thereby stimulating autophagy. During ischemia, Trx1 was oxidized at Cys32-Cys35 of the oxidoreductase catalytic center and S-nitrosylated at Cys73. Unexpectedly, Atg7 Cys545-Cys548 reduced the disulfide bond in Trx1 at Cys32-Cys35 through thiol-disulfide exchange and this then allowed NO to be released from Cys73 in Trx1 and transferred to Atg7 at Cys402. Experiments conducted with Atg7 C402S-knockin mice showed that S-nitrosylation of Atg7 at Cys402 promotes autophagy by stimulating E1-like activity, thereby protecting the heart against ischemia. These results suggest that the thiol-disulfide exchange and the NO transfer are functionally coupled, allowing oxidized Trx1 to mediate a salutary effect during myocardial ischemia through transnitrosylation of Atg7 and stimulation of autophagy.
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Isquemia Miocárdica , Tiorredoxinas , Animais , Camundongos , Autofagia , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Cisteína/metabolismo , Dissulfetos , Isquemia Miocárdica/genética , Oxirredução , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMO
C-terminal tensin-like (CTEN) is a tensin family protein typically localized to the cytoplasmic side of focal adhesions, and primarily contributes to cell adhesion and migration. Elevated expression and nuclear accumulation of CTEN have been reported in several types of cancers and found to be associated with malignant behaviors. However, the function of nuclear CTEN remains elusive. In this study, we report for the first time that nuclear CTEN associates with chromatin DNA and occupies the region proximal to the transcription start site in several genes. The mRNA expression level of CTEN positively correlates with that of one of its putative target genes, cell division cycle protein 27 (CDC27), in a clinical colorectal cancer dataset, suggesting that CTEN may play a role in the regulation of CDC27 gene expression. Furthermore, we demonstrated that CTEN is recruited to the promoter region of the CDC27 gene and that the mRNA expression and promoter activity of CDC27 are both reduced when CTEN is downregulated. In addition, we found that enhanced nuclear accumulation of CTEN in HCT116 cells by overexpression of CTEN fused with nuclear localization signals increases CDC27 transcript levels and promoter activity. The increased nuclear-localized CTEN also significantly promotes cell migration, and the migratory ability is suppressed when CDC27 is knocked down. These results demonstrate that nuclear CTEN regulates CDC27 expression transcriptionally and promotes cell migration through CDC27. Our findings provide new insights into CTEN moonlighting in the nucleus as a DNA-associated protein and transcriptional regulator involved in modulating cancer cell migration.
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Proteínas dos Microfilamentos , Neoplasias , Humanos , Tensinas/genética , Tensinas/metabolismo , Proteínas dos Microfilamentos/genética , Movimento Celular , Adesão Celular/fisiologia , RNA Mensageiro/genética , Subunidade Apc3 do Ciclossomo-Complexo Promotor de AnáfaseRESUMO
Piriformospora indica is an important endophytic fungus with broad potential for alleviating biotic and abiotic stress on host plants. This study monitored the growth dynamics of P. indica on five commonly used artificial media for microorganisms and analyzed its metabolic characteristics using Biolog Phenotype Microarray (PM) technology. The results showed that P. indica grew fastest on Potato Dextrose Agar (PDA), followed by Kidney Bean Agar (KBA), Alkyl Ester Agar (AEA), Oatmeal Agar (OA), and Luria-Bertani Agar (LB), and the most suitable medium for spore production was OA. Using Biolog PM1-10, 950 metabolic phenotypes of P. indica were obtained. P. indica could metabolize 87.89% of the tested carbon sources, 87.63% of the tested nitrogen sources, 96.61% of the tested phosphorus sources, and 100% of the tested sulfur sources. P. indica displayed 92 kinds of tested biosynthetic pathways, and it could grow under 92 kinds of tested osmotic pressures and 88 kinds of tested pH conditions. PM plates 1-2 revealed 43 efficient carbon sources, including M-Hydroxyphenyl acid, N-Acetyl-D-Glucosamine, Tyramine, Maltotrios, α-D-Glucosine, I-Erythritol, L-Valine, D-Melezitose, D-Tagatose, and Turanose. PM plates 3,6-8 indicated 170 efficient nitrogen sources, including Adenosine, Inosine Allantoin, D, L-Lactamide, Arg-Met, lle-Trp, Ala-Arg, Thr-Arg, Trp-Tyr, Val-Asn, Gly-Gly-D-Leu, Gly-Gly-Phe, and Leu-Leu-Leu. This study demonstrates that P. indica can metabolize a variety of substrates, such as carbon and nitrogen sources, and has a wide range of environmental adaptability. The growth dynamics on artificial culture media and metabolic phenotypes of P. indica can be used to investigate its biological characteristics, screen for more suitable growth and sporulation conditions, and elucidate the physiological mechanisms that enhance the stress resistance of host plants. This study provides a theoretical basis for its better application in agriculture.
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Background: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown. Methods: A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing. Results: Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni's correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients' gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P<0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients (P<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative. Conclusion: The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.
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Microbioma Gastrointestinal , Cirrose Hepática Biliar , Feminino , Microbioma Gastrointestinal/genética , Genes MHC da Classe II , Antígenos HLA/genética , Cadeias HLA-DRB1/genética , Humanos , Cirrose Hepática Biliar/genética , Masculino , RNARESUMO
Diabetes mellitus (DM) is a chronic metabolic disease. If blood glucose is poorly controlled, it will cause a variety of chronic complications. Therefore, the issue of healthcare in diabetic patients is a problem that cannot be ignored. In this study, we aim to investigate the correlation between sociodemographic characteristics, self-management, and glycated hemoglobin (HbA1c) values in patients with type 2 diabetes treated with insulin. A total of 300 type 2 diabetic patients treated with insulin were enrolled. Type 2 diabetic patients treated with insulin had a significant negative correlation of HbA1c value to self-management total score. The lower the HbA1c value, the better the self-management of type 2 diabetic patients treated with insulin is. It is recommended that scale assessment tools be used to identify problems, improve the self-management ability of type 2 diabetic patients, and problem solve in patients in order to facilitate the effectiveness of blood glucose control of type 2 diabetic patients.
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PERM1 (PGC-1/ERR-induced regulator in muscle 1) is a muscle-specific protein induced by PGC-1 and ERRs. Previous studies have shown that PERM1 promotes mitochondrial biogenesis and metabolism in cardiomyocytes in vitro. However, the role of endogenous PERM1 in the heart remains to be investigated with loss-of-function studies in vivo. We report the generation and characterization of systemic Perm1 knockout (KO) mice. The baseline cardiac phenotype of the homozygous Perm1 KO mice appeared normal. However, RNA-sequencing and unbiased pathway analyses showed that homozygous downregulation of PERM1 leads to downregulation of genes involved in fatty acid and carbohydrate metabolism in the heart. Transcription factor binding site analyses suggested that PPARα and PGC-1α are involved in changes in the gene expression profile. Chromatin immunoprecipitation assays showed that PERM1 interacts with the proximal regions of PPAR response elements (PPREs) in endogenous promoters of genes involved in fatty acid oxidation. Co-immunoprecipitation and reporter gene assays showed that PERM1 promoted transcription via the PPRE, partly in a PPARα and PGC-1α dependent manner. These results suggest that endogenous PERM1 is involved in the transcription of genes involved in fatty acid oxidation through physical interaction with PPARα and PGC-1α in the heart in vivo.
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Metabolismo dos Lipídeos , Proteínas Musculares , PPAR alfa , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Animais , Ácidos Graxos , Camundongos , Camundongos Knockout , Proteínas Musculares/metabolismo , Miócitos Cardíacos , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
Cardiac paragangliomas are exceedingly rare. Herein, we describe a patient with a large dopaminesecreting cardiac paraganglioma who had a history of pheochromocytoma after right adrenalectomy. The cardiac surgery was uneventful and without blood pressure fluctuations.The measurement of plasma-free metanephrines or urinary fractionated metanephrines is used as an initial screening test for pheochromocytoma or paraganglioma detection. However, these results must be combined with those of a plasma 3-methoxytyramine test to accurately establish the rare dopaminergic phenotype of pheochromocytomas or paragangliomas, if suspected. F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based positron emission tomography (PET) and PET-computed tomography are relatively sensitive and specific; therefore, these techniques are recommended for patients with pheochromocytomas or paragangliomas before operation or during postoperative follow-up.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Dopamina , Humanos , Paraganglioma/diagnóstico , Paraganglioma/cirurgia , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/cirurgia , Base do CrânioRESUMO
BACKGROUND/PURPOSE: Data about volumetric remodeling of the provisional extension to induce complete attachment (PETTICOAT) technique on DeBakey type IIIb aortic dissection in acute and subacute phases were scarce. The proper timing to perform this technique to promote false lumen reduction was also unknown. METHODS: Patients with DeBakey type IIIb aortic dissection who underwent the PETTICOAT technique between December 2005 and March 2017 were reviewed and divided into acute (treatment occurred â¦14 days after symptom onset) and subacute (15-90 days) groups. Remodeling parameters of the true and false lumens were analyzed. Receiver operating characteristic curve was used to deduce the timing of this technique. RESULTS: In the 2-year follow-up, the acute group (N = 20) demonstrated significant true lumen expansion and false lumen regression in the thoracic, abdominal, and total aorta. However, the subacute group (N = 20) only showed significant shrinkage in the false lumen of the thoracic and total aorta. Using PETTICOAT technique within 36 days after the aortic event may result in better total false lumen reduction. CONCLUSION: For DeBakey type IIIb aortic dissection, more prominent true lumen expansion and false lumen reduction were noted when using the PETTICOAT technique in the acute phase. When performed within 36 days after symptoms onset, the PETTICOAT technique may potentiate better total false lumen regression.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aorta , Humanos , Estudos Retrospectivos , Stents , Resultado do Tratamento , Remodelação VascularRESUMO
Background: A variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions. Methods: We retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used. Results: Five clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis. Conclusion: Clustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.
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Autoanticorpos , Cirrose Hepática Biliar , Humanos , Masculino , Feminino , Autoanticorpos/análise , Estudos Retrospectivos , Cirrose Hepática Biliar/diagnóstico , Pacientes Internados , Anticorpos Antinucleares/análise , Cirrose Hepática , China/epidemiologiaRESUMO
This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05-4 µg/ml for fluconazole, 0.25-1 µg/ml for amphotericin B; 0.0625-2 µg/ml for 5-fluorocytosine, 0.0625-0.25 µg/ml for itraconazole, 0.0078-0.25 µg/ml for voriconazole, 0.0313-0.5 µg/ml for posaconazole, 0.0020-0.125 µg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1-16 µg/ml for fluconazole, 0.125-1 µg/ml for 5-fluorocytosine, 0.25-1 µg/ml for amphotericin B, 0.0625-0.25 µg/ml for itraconazole, 0.0156-0.125 µg/ml for voriconazole, 0.0156-0.25 µg/ml for posaconazole, and 0.0078-0.125 µg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.
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Fibrosis is a hallmark of heart disease independent of etiology and is thought to contribute to impaired cardiac dysfunction and development of heart failure. However, the underlying mechanisms that regulate the differentiation of fibroblasts to myofibroblasts and fibrotic responses remain incompletely defined. As a result, effective treatments to mitigate excessive fibrosis are lacking. We recently demonstrated that the Hippo pathway effector Yes-associated protein (YAP) is an important mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Yet, whether YAP activation in cardiac fibroblasts is sufficient to drive fibrosis, and how fibroblast YAP affects myocardial inflammation, a significant component of adverse cardiac remodeling, are largely unknown. In this study, we leveraged adeno-associated virus (AAV) to target cardiac fibroblasts and demonstrate that chronic YAP expression upregulated indices of fibrosis and inflammation in the absence of additional stress. YAP occupied the Ccl2 gene and promoted Ccl2 expression, which was associated with increased macrophage infiltration, pro-inflammatory cytokine expression, collagen deposition, and cardiac dysfunction in mice with cardiac fibroblast-targeted YAP overexpression. These results are consistent with other recent reports and extend our understanding of YAP function in modulating fibrotic and inflammatory responses in the heart.
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Dependovirus/genética , Fibrose/patologia , Vetores Genéticos , Inflamação/genética , Miofibroblastos/metabolismo , Fatores de Transcrição/genética , Animais , Regulação da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Ratos , Ratos WistarRESUMO
[Figure: see text].
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Antioxidantes/metabolismo , Citocinas/metabolismo , Cardiomiopatias Diabéticas/enzimologia , Miócitos Cardíacos/enzimologia , Nicotinamida Fosforribosiltransferase/metabolismo , Estresse Oxidativo , Animais , Apoptose , Autofagia , Células Cultivadas , Citocinas/genética , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Fibrose , Glutationa/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/genética , Mitocôndrias Cardíacas/patologia , Mitofagia , Miócitos Cardíacos/patologia , NAD/metabolismo , NADP/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Ratos Wistar , Sirtuínas/genética , Sirtuínas/metabolismo , Tiorredoxinas/metabolismoRESUMO
OBJECTIVE: Patients diagnosed of DeBakey type III aortic dissection with partial thrombosis of false lumen (FL) have a higher mortality rate. However, IIIb dissections with full patent FL tend to exhibit a partially thrombosed FL quickly after thoracic endovascular aortic repair (TEVAR); thus, we investigated survival and aortic remodeling in this population. METHODS: We reviewed computed tomography aortograms (CTAs) of 123 patients with TEVAR-treated IIIb aortic dissections from July 2006 to June 2015; contrast density of CTAs represented intraluminal flow. Patients were selected to fit in 2 groups of FL in term of FL contrast density: low flow (LF) group (non-opacification in the midway of FL) and high flow (HF) group (full patent FL). RESULTS: Surgical mortality was 10.3% in the HF group and 4.5% in the LF group (n = 61; LF = 22; HF = 39). 3 patients in the HF group suffered from lethal aortic rupture in 10 days postoperatively. The HF group showed significant increase in maximal diameter, and had larger thoracic (+4.00 ± 2.68 vs -1.16 ± 3.42 mm, P < .001) aortic diameter expansion from preoperation to one week postoperation. Both groups exhibited significant favorable thoracic TL expansion and maximal aortic diameter shrinkage in postoperative one week to one year. However, HF group displayed less thoracic aortic FL regression (-70.9 ± 83.5 vs -113.9 ± 95.0 cm3, P = .1) and TL expansion (+14.5 ± 27.2 vs +36.8 ± 28.3 cm3, P = .008) when compared to LF group. CONCLUSIONS: Preoperative HF in the FL has an unfavorable effect on thoracic aortic diameter in one week post-TEVAR. This might increase the risk of aortic rupture.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aortografia , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Remodelação VascularRESUMO
OBJECTIVES: To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA). METHODS: From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up. RESULTS: The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p < 0.001). No significant difference was observed for the incidence of type 1a (IBD/COCh = 3.33%/6.45%, p > 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p > 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64). CONCLUSIONS: The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.