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BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.
Assuntos
MicroRNAs , RNA Longo não Codificante , Calcificação Vascular , Humanos , Ratos , Animais , MicroRNAs/metabolismo , Aldosterona/toxicidade , RNA Longo não Codificante/metabolismo , Osteogênese , Calcificação Vascular/induzido quimicamente , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismoRESUMO
BACKGROUND: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. METHODS: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. RESULTS: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. CONCLUSIONS: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00005130.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Síndrome Metabólica , Obesidade Metabolicamente Benigna , Adulto , Índice de Massa Corporal , Cálcio , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade Metabolicamente Benigna/complicações , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Fenótipo , Fatores de RiscoRESUMO
Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.
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Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Aterosclerose , Humanos , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Peróxido de Hidrogênio/metabolismo , Secretoma , Músculo Liso Vascular/metabolismo , Cicloeximida/metabolismo , Proteômica , Tecido Adiposo/metabolismo , Aneurisma Aórtico/metabolismo , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aorta Abdominal/cirurgia , Aterosclerose/metabolismo , Adipócitos Marrons , Camundongos Endogâmicos C57BLRESUMO
Insecticides have been widely used for the control of insect pests that have a significant impact on agriculture and human health. A better understanding of insecticide targets is needed for effective insecticide design and resistance management. Pymetrozine, afidopyropen and flonicamid are reported to target on proteins that located on insect chordotonal organs, resulting in the disruption of insect coordination and the inhibition of feeding. In this study, we systematically examined the susceptibility of six Drosophila melanogaster mutants (five transient receptor potential channels and one mechanoreceptor) to three commercially used insecticides, in order to identify the receptor subunits critical to the insect's response to insecticides. Our results showed that iav1, nan36aand wtrw1 mutants exhibited significantly reduced susceptibility to pymetrozine and afidopyropen, but not to flonicamid. The number of eggs produced by the three mutant females were significantly less than that of the w1118 strain. Meanwhile, the longevity of all male mutants and females of nan36a and wtrw1 mutants was significantly shorter than that of the w1118 strain as the control. However, we observed no gravitaxis defects in wtrw1 mutants and the anti-gravitaxis of wtrw1 mutants was abolished by pymetrozine. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that Nan as a TRPV subfamily member located in Drosophila chordotonal neurons, acting as a target of pymetrozine, which interferes with Drosophila and causes motor deficits with gravitaxis defects. Taken together, this study elucidates the interactions of pymetrozine and afidopyropen with TRPV channels, Nan and Iav, and TRPA channel, Wtrw. Our research provides another evidence that pymetrozine and afidopyropen might target on nan, iav and wtrw channels and provides insights into the development of sustainable pest management strategies.
Assuntos
Drosophila melanogaster , Inseticidas , Animais , Feminino , Humanos , Drosophila melanogaster/genética , Inseticidas/farmacologia , Genética Reversa , Drosophila/genéticaRESUMO
PURPOSE: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.
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Photooxidation of As(III) by TiO2 is a complicated process in which the oxidation mechanisms are always controversial. In this study, the enhanced photooxidation rates of As(III) with increasing pH values from 8.0 to 11.0 indicate the high photocatalytic reactivity of TiO2 under alkaline conditions. Moreover, As(III) improves the production of H2O2, indicating H-abstraction from As(III) (soluble or adsorbed) for H2O2 production. Although O2Ë-, h+, ËOH and -OOH are always regarded as the reactive oxygen species in the UV-TiO2 system, the superoxo and peroxo species formed on the surface of TiO2 also contribute to As(III) oxidation. The As(III)-O-Ti(IV) surface complexes formed on TiO2, as well as the decreased bandgaps of TiO2 with increasing concentrations of As(III) indicate that the ligand-to-metal charge transfer (LMCT) pathway also contributes to the oxidation of As(III) under alkaline conditions. Electrochemical analyses further reveal that As(III) enhances the electron density on the surface of TiO2, thereby improving the catalytic reactivity of TiO2. We therefore suggest that H-abstraction from As(III) or H2O to the formed superoxo and peroxo species results in the formation of H2O2, accompanied by the oxidation of As(III). This enriches our knowledge on the oxidation of As(III), as well as other contaminants rich in -OH groups during the photocatalytic oxidation processes.
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Arsenitos , Arsenitos/química , Peróxido de Hidrogênio/química , Ligantes , Metais , Titânio/químicaRESUMO
Biotic and abiotic oxidation of Mn(II) in aqueous environments is an important process for the cycling of many elements. However, the mechanism involved in photocatalytic oxidation of Mn(II) has not been clearly elucidated yet. In this study, the photocatalytic oxidation of Mn(II) on the surface of self-doped Bi2+xWO6 (Bi2.15WO6) under visible light was conducted. Kinetics results show that visible light apparently accelerates the oxidation of Mn(II) to Mn(III, IV) oxides on Bi2.15WO6. The average oxidation states (AOS) of manganese reach 2.18 after 80 min of reaction under visible light at pH 8.50. Characterizations indicate the formation of Bi(III)-O-Mn(II) surface complexes between Mn(II) and surface Bi(III) on Bi2.15WO6, which then decreases the bandgap of [Bi2.15WO6 + Mn(II)]light (2.53 eV) compared with those of [Bi2.15WO6 + Mn(II)]dark (2.72 eV) and pure Bi2.15WO6 (2.86 eV), suggesting the contribution of the ligand-to-metal charge transfer (LMCT) pathway to the photocatalytic oxidation of Mn(II). Moreover, the addition of inorganic oxidants with strong oxidizing capacities (such as Cr2O72-, NO3- or NO2-) significantly increases the oxidation rate of Mn(II), further verifying the contribution of the LMCT pathway to Mn(II) oxidation. We therefore suggest that the LMCT pathway is one of the important oxidation routes for Mn(II) oxidation on Bi2.15WO6 under visible light.
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PURPOSE: Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000-2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 < CAC < 100 or CAC ≥ 100 at baseline, respectively. RESULTS: Dietary zinc intake was 8.4 ± 4.5 mg/day and 2537 (48.9%) of the included participants had CAC at baseline. Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-9.1 years), 2704 (52.1%) participants had CAC progression. In the fully adjusted model, higher dietary zinc was associated with a lower risk of CAC progression in both men (hazard ratio [HR] 0.697, 95% confidence interval [CI] 0.553-0.878; p = 0.002) and women (HR 0.675; 95% CI 0.496-0.919; p = 0.012, both comparing extreme groups). Furthermore, such an inverse association was attributable to dietary zinc intake from non-red meat (p < 0.05), rather than red meat sources (p > 0.05). CONCLUSIONS: In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression. CLINICAL TRIAL REGISTRATION NUMBER: The MESA trial was registered at clinicaltrials.gov as NCT00005487.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Cálcio , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/prevenção & controle , Vasos Coronários/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , ZincoRESUMO
It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)-enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α-SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3-MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aldosterona/metabolismo , Autofagia , Fosfatos/metabolismo , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Aldosterona/farmacologia , Animais , Autofagia/efeitos dos fármacos , Biomarcadores , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Expressão Gênica , Genes Reporter , Camundongos , Modelos Biológicos , Osteogênese/efeitos dos fármacos , Fosfatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Calcificação Vascular/patologiaRESUMO
BACKGROUND: Percutaneous endoscopic decompression (PED) is considered a minimally invasive and safe procedure in lumbar degenerative disease. Few authors report the success of PED for thoracic spinal stenosis (TSS) with thoracic myelopathy. The objective of this study was to compare the outcome of PED versus posterior decompressive laminectomy (PDL) for TSS. METHODS: We retrospectively reviewed 30 consecutive patients who underwent surgery for single-level TSS from January 1, 2015 to May 1, 2019.These patients were divided into PED (n = 16) and PDL(n = 14) group. Preoperative demographic characteristics and perioperative outcomes were reviewed. Pre- and postoperative neurological status was evaluated using the modified Japanese Orthopaedic Association (mJOA) score and the recovery rate (RR). RESULTS: The patients' mean age was 57.3 years (27-76) in PED group and 58.8 years (34-77) in PDL group. No statistical difference was found between two groups with regards to neurological status at pre-operative and final follow-up. The RR in PED group achieved the same improvement as PDL group (87.5% vs 85.7%, P > 0.05), while the PED brought advantages in operative time(m) (86.4 vs 132.1, p < 0.05), blood loss (mL) (18.21 vs 228.57, p < 0.05),drainage volume(mL) (15.5 vs 601.4, p < 0.05), and hospital stay (d) (3.6 vs 5.6, p < 0.05). CONCLUSIONS: Both PED and PDL showed favorable outcome in the treatment of TSS. Besides, PED had advantages in reducing traumatization. In terms of perioperative quality of life, PED could be an efficient supplement to traditional posterior decompressive laminectomy in patients with TSS.
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Estenose Espinal , Descompressão Cirúrgica , Humanos , Laminectomia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Resultado do TratamentoRESUMO
Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.
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Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/virologia , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Ativação Viral/imunologia , Adolescente , Adulto , Idoso , Antígenos CD34/imunologia , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/virologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Transplante HaploidênticoRESUMO
There are limited reports of central nervous system (CNS) invasive fungal disease (IFD) in allogeneic stem cell transplantation (HSCT) recipients. We aimed to describe the clinical characteristics of and the risk factors for CNS-IFD. We retrospectively reviewed consecutive HSCT patients at Peking University Institute of Hematology during a 10-year period. A total of 29 patients were diagnosed with CNS-IFD. The median onset of CNS-IFD was 173 (range, 24 to 972) days after HSCT. The most frequent pathogen was Aspergillus, and the most common clinical symptoms and signs were space-occupying presentations. We found that prior pulmonary IFD (P < .001; hazard ratio, 62.746; 95% confidence interval, 14.28 to 275.27) was the only risk factor associated with occurrence of CNS-IFD. Poor response at 6 weeks after treatment (P = .045; hazard ratio, 2.574; 95% confidence interval, 1.021 to 6.487) was the only risk factor predicting the involvement of the CNS in pulmonary IFD. Overall survival was 24.2% at the last follow-up, with a median of 289 (range, 27 to 3341) days after transplantation. We conclude that patients with pulmonary IFD had higher risk of CNS-IFD, especially in those with poor response after 6 weeks of treatment. The prognosis of CNS-IFD was very poor after HSCT.
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Doenças do Sistema Nervoso Central/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Doenças do Sistema Nervoso Central/patologia , Criança , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Resultado do Tratamento , Adulto JovemRESUMO
CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells (VECs) and up-regulated during angiogenesis. In this study, we investigated whether CD151 regulated migration, proliferation, tube formation and angiogenesis of human umbilical VECs (HUVECs) with activation of C-Met. Moreover, we studied whether CD151 could affect the angiogenic molecules such as nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF). The expression of CD151 was determined by Western blotting. The cell proliferation assay was performed using the cell counting kit-8 (CCK-8) method and cell migration was assessed in microchemotaxis chambers by using fetal bovine serum (FBS) as the chemotactic stimulus. The angiogenic molecules were evaluated using ELISA. The NO level was detected using NO detection kit. The potential involvement of various signaling pathways was explored using relevant antibodies. We found that proliferation, migration and tube formation of HUVECs were promoted by CD151 with activation of C-Met, FAK and CDC42, while they were suppressed with CD151 knockdown by RNAi. Similarly, the levels of NO, VCAM-1 and VEGF in HUVECs were increased by CD151, but they were inhibited with CD151 knockdown by RNAi. These data suggested that CD151 could promote migration, proliferation, tube formation and angiogenesis of HUVECs, which was possibly related to the C-Met signaling pathways.
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Neovascularização Fisiológica , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Tetraspanina 24/metabolismo , Sequência de Bases , Células Endoteliais da Veia Umbilical Humana , Humanos , RNA Interferente Pequeno/genética , Tetraspanina 24/genéticaRESUMO
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (Siniperca chuatsi). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection.
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Proteínas do Capsídeo/metabolismo , Caveolina 1/metabolismo , Interações Hospedeiro-Patógeno , Iridoviridae/patogenicidade , Mapeamento de Interação de Proteínas , Animais , Linhagem Celular , Centrifugação , Imunoprecipitação , PerciformesRESUMO
The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement.
Assuntos
Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/fisiopatologia , Hipotensão/diagnóstico por imagem , Hipotensão/fisiopatologia , Inconsciência/diagnóstico por imagem , Inconsciência/fisiopatologia , Adulto , Idoso , Angiografia , Ruptura Aórtica/epidemiologia , Feminino , Humanos , Hipotensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico por imagem , Dor/epidemiologia , Dor/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Inconsciência/epidemiologiaRESUMO
PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Epirubicina , Neoplasias Hepáticas/patologia , Microesferas , Estudos Prospectivos , Resultado do Tratamento , Quimioembolização Terapêutica/métodos , Doxorrubicina , Estudos RetrospectivosRESUMO
BACKGROUND: Infectious spleen and kidney necrosis virus (ISKNV) belongs to the genus Megalocytivirus from the family Iridoviridae. Megalocytivirus causes severe economic losses to tropical freshwater and marine culture industry in Asian countries and is devastating to the mandarin fish farm industry in China particularly. METHODS: We investigated the involvement of microfilaments in the early and late stages of ISKNV infection in MFF-1 cells by selectively perturbing their architecture using well-characterized inhibitors of actin dynamics. The effect of disruption of actin cytoskeleton on ISKNV infection was evaluated by indirect immunofluorescence analysis or real-time quantitative PCR. RESULTS: The depolymerization of the actin filaments with cytochalasin D, cytochalasin B, or latrunculin A reduced ISKNV infection. Furthermore, depolymerization of filamentous actin by inhibitors did not inhibit binding of the virus but affected virus internalization in the early stages of infection. In addition, the depolymerization of actin filaments reduced total ISKNV production in the late stages of ISKNV. CONCLUSIONS: This study demonstrated that ISKNV required an intact actin network during infection. The findings will help us to better understand how iridoviruses exploit the cytoskeleton to facilitate their infection and subsequent disease.
Assuntos
Citoesqueleto de Actina/metabolismo , Iridoviridae/fisiologia , Citoesqueleto de Actina/genética , Animais , Linhagem Celular , Peixes , Técnica Indireta de Fluorescência para Anticorpo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Subintimal angioplasty (SIA) has become an established percutaneous procedure for the treatment of symptomatic lower limb arterial occlusions in recent years. However, the clinical benefits of this practice remain unclear. The aim of the review was to determine the effectiveness of SIA on clinical outcomes. OBJECTIVES: To assess the effectiveness of SIA versus any other treatment for patients with chronic lower limb artery occlusion. This will be determined by the effects on clinical improvement, technical success rate, patency rate, limb salvage rate, and morbidity rates. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Clinical trials databases were also searched. SELECTION CRITERIA: We planned to include data from randomized controlled trials comparing the effectiveness of SIA and any other management method in the treatment of chronic lower limb arterial occlusion. DATA COLLECTION AND ANALYSIS: Two authors evaluated the trials identified from the searches for appropriateness of inclusion. MAIN RESULTS: There were no randomized controlled trials in which SIA was compared with any other treatment. AUTHORS' CONCLUSIONS: Randomized controlled trial evidence for the effectiveness of SIA is lacking. There is a need for high-quality randomized controlled trials comparing SIA with any other treatment.
Assuntos
Angioplastia/métodos , Arteriopatias Oclusivas/terapia , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares Periféricas/terapia , Túnica Íntima , HumanosRESUMO
Tiger frog virus (TFV), in the genus Ranavirus of the family Iridoviridae, causes high mortality of cultured tiger frog tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH(4)Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.
Assuntos
Cavéolas/fisiologia , Endocitose/fisiologia , Fígado/virologia , Ranavirus/patogenicidade , Internalização do Vírus , Actinas/metabolismo , Animais , Colesterol/metabolismo , Dinaminas/metabolismo , Células Hep G2/virologia , Humanos , Concentração de Íons de Hidrogênio , Fígado/citologiaRESUMO
Based on the characteristics of optical absorption gas sensing technology (OA-GST) and spatial heterodyne spectroscopy (SHS), a novel type of visual gas sensing technology (V-GST) can present the invisible gas information in the form of two-dimensional visual fingerprint, which has attracted people's attention. In this paper, we have realized the NO2 detection of V-GST in the laboratory environment for the first time. Experimental results show that: V-GST not only has different interferogram response to different spectra, but also has good response to different concentrations of NO2, which lays a foundation for the application of this technology in gas sensing. And the average classification recognition rate of the system for different band NO2 response data is over 80%, which verifies the effectiveness of the V-GST in gas detection.