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BACKGROUND: The relationship between rare variants in Ring finger protein 213 (RNF213) and intracranial atherosclerosis (ICAS) remained unelucidated. Using whole-exome sequencing (WES) and high-resolution magnetic resonance imaging (HR-MRI), this study aimed at investigating the association between rare RNF213 variants and ICAS within a Chinese community-dwelling population. METHODS: The present study included 821 participants from Shunyi cohort. Genetic data of rare RNF213 variants were acquired by WES and were categorized by functional domains. Intracranial and extracranial atherosclerosis were assessed by brain HR-MRI and carotid ultrasound, respectively. Logistic regression and generalized linear regression were applied to evaluate the effects of rare RNF213 variants on atherosclerosis. Stratification by age were conducted with 50 years old set as the cutoff value. RESULTS: Ninety-five participants were identified as carriers of rare RNF213 variants. Carotid plaques were observed in 367 (44.7 %) participants, while ICAS was identified in 306 (37.3 %). Rare variants of RNF213 was not associated with ECAS. Employing HR-MRI, both the presence of rare variants (ß = 0.150, P = 0.025) and numerical count of variants (ß = 0.182, P = 0.003) were significantly correlated with ICAS within the group of age ≤50 years. Both variant existence (ß = 0.154, P = 0.014) and variant count (ß = 0.188, P = 0.003) were significantly associated with plaques in middle cerebral arteries within younger subgroup, rather than basilar arteries. Furthermore, a significant association was observed between variants that located outside the N-arm domain and ICAS in the younger subgroup (OR = 2.522, P = 0.030). Statistical results remained robust after adjusted for age, gender, and cardiovascular risk factors. CONCLUSIONS: Rare variants of RNF213 is associated with age-related ICAS in general Chinese population, highlighting the potential role of RNF213 as a genetic contributor to early-onset ICAS.
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Adenosina Trifosfatases , Idade de Início , Predisposição Genética para Doença , Arteriosclerose Intracraniana , Fenótipo , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Masculino , Pessoa de Meia-Idade , Feminino , Arteriosclerose Intracraniana/genética , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/etnologia , China/epidemiologia , Adulto , Fatores de Risco , Adenosina Trifosfatases/genética , Estudos de Associação Genética , Sequenciamento do Exoma , Medição de Risco , Idoso , Placa Aterosclerótica/genética , Povo Asiático/genética , Imageamento por Ressonância Magnética , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etnologia , População do Leste AsiáticoRESUMO
OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ï¼0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ï¼ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ï¼ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ï¼ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.
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The indications and surgical techniques for airway stenosis (AS) repair among patients with bridging bronchus (BB) and congenital heart disease (CHD) have not been fully established. We sought to provide our experience with tracheobronchoplasty in a large series of BB patients with AS and CHD. Eligible patients were retrospectively enrolled from June 2013 to December 2017 and were followed up to December 2021. Epidemiological, demographic, clinical, imaging, surgical management, and outcome data were obtained. 5 tracheobronchoplasty techniques including 2 novel modified ones were performed. We included 30 BB patients with AS and CHD. Tracheobronchoplasty was indicated in them. 27 (90%) patients underwent tracheobronchoplasty. But 3 (10%) refused AS repair. 4 subtypes of the BB and 5 main sites of AS were identified. 6 (22.2%) cases, including one death, had severe postoperative complications associated with being underweight at surgery, preoperative mechanical ventilation, and more types of CHD. 3 cases were lost to follow-up. 18 (78.3%) of the survivors remained asymptomatic, and 5 (21.7%) had stridor, wheezing, or polypnea after exercise. 2 patients out of the three who did not undergo airway surgery died, and the one survivor had a poor quality of life. Good outcomes can be achieved in BB patients with AS and CHD who undergo proper tracheobronchoplasty techniques guided by specified criteria, but severe postoperative complications should be well managed.
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BACKGROUND: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. OBJECTIVES: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. METHODS: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. RESULTS: DEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1ß, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. CONCLUSIONS: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.
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Trifosfato de Adenosina , Neutrófilos , Animais , Anti-Inflamatórios , Glicemia , Bovinos , Colesterol , Citrato (si)-Sintase , Dexametasona/farmacologia , Transportador de Glucose Tipo 1 , Glucosefosfato Desidrogenase , Glicogênio , Interleucina-6 , Masculino , Sódio , Ácidos Tricarboxílicos , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: Fabry disease (FD) is an X-linked lysosomal storage disease caused by the mutation in the α-galactosidase A gene that leads to a consequently decreased α-galactosidase A enzyme activity and a series of clinical presentations. However, FD accompanied with aseptic meningitis can be relatively scarce and rarely reported, which leads to significant clinical misdiagnosis of this disease. METHODS: Sixteen patients diagnosed with FD based on a decreased activity of α-galactosidase A enzyme and/or genetic screening were identified through a 6-year retrospective chart review of a tertiary hospital. Clinical presentations, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analyzed in cases of aseptic meningitis associated with FD. RESULTS: Three out of 16 cases exhibited aseptic meningitis associated with FD. There was one female and two male patients with a mean age of 33.3 years. A family history of renal failure or hypertrophic cardiomyopathy was found in 3 cases. All cases presented with a persistent or intermittent headache and recurrent ischemic stroke. The cerebrospinal fluid analyses showed mild pleocytosis in 2 patients and an elevated level of protein in all patients. Cerebrospinal fluid cytology revealed activated lymphocytes, suggesting the existence of aseptic meningitis. In the literature review, up to 9 cases presenting with FD and aseptic meningitis were found, which bore a resemblance to our patients in demographic and clinical characteristics. CONCLUSION: Our cases suggested that aseptic meningitis in FD might be under-detected and easily misdiagnosed, and should be more thoroughly examined in further cases.
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Doença de Fabry , Meningite Asséptica , Adulto , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningite Asséptica/diagnóstico , Meningite Asséptica/tratamento farmacológico , Meningite Asséptica/etiologia , Estudos Retrospectivos , alfa-Galactosidase/uso terapêuticoRESUMO
Objective: To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients. Methods: Patients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed. Results: A total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions. Conclusion: The etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies.
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Objectives: This study aimed to assess the associations of caesarean delivery (CD) with risk of wheezing diseases and changes of immune cells in children. Design: The cross-sectional study was conducted between May, 2020 and April, 2021. Setting and participants: The study was conducted in Shanghai Children's Medical Center, Shanghai, China. A total of 2079 children with a mean age of 36.97 ± 40.27 months and their guardians were included in the present study via face-to-face inquiry and physical examination by clinicians. Methods: Logistic regression was applied to estimate odds ratio (ORs) and 95% confidence intervals (CIs) for the association between CD and first episode of wheezing (FEW) or asthma. Models were adjusted for premature or full-term delivery, exclusive breastfeeding (at least 4 months) or not. Results: Among the 2079 children, 987 children (47.47%) were born by CD and 1092 (52.53%) by vaginal delivery (VD). Children delivered by caesarean had significantly lower gestational age (P<0.01) compared with those who delivered vaginally. Our results also showed that CD was related to increased risk of FEW by the age of 3(adjusted OR 1.50, 95%CI 1.06, 2.12) and increased tendency to develop asthma by the age of 4 (adjusted OR 3.16, 95%CI 1.25, 9.01). The subgroup analysis revealed that the negative effects of CD on asthma were more obvious in children without exclusive breastfeeding (adjusted OR 4.93, 95%CI 1.53, 21.96) or without postnatal smoking exposure (adjusted OR 3.58, 95%CI 1.20, 13.13). Furthermore, compared with children born through VD, a significant change of the T cells (increased proportion of CD4+ T cells and decreased number and proportion of CD8+ T cells) were observed before the age of one in the CD group. However, the changes were insignificant in children over 1 year old. Conclusions: This study showed age-dependent associations of CD with asthma and FEW in offspring. Moreover, CD appeared to have an effect on the cellular immunity in infants, the disorder of which may contribute to the development of asthma in children.
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Asma/epidemiologia , Asma/etiologia , Cesárea/efeitos adversos , Suscetibilidade a Doenças/imunologia , Sons Respiratórios/etiologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Idade de Início , Biomarcadores , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Imunidade , Imunofenotipagem , Masculino , Razão de Chances , Vigilância em Saúde Pública , Fatores de RiscoRESUMO
Airborne particulate matter (PM) primarily resulting from fossil fuel burning is an increasingly global issue. In this work, an intrinsically fragile TiO2 nanofibrous mat was facilely engineered with good structural integrity, flexibility, foldability, and high-temperature resistance (~1300 °C), by suppressing the sintering (i.e., growth) of nanocrystallites in each single nanofiber. Such functionalization enables self-regenerative air filtration for PM capture and in situ catalytic elimination in a "one-stone-two-birds" approach. Finite element analysis simulation revealed the retained nanopores in each anti-sintering nanofiber could facilitate the air flow during filtration. Without any chemical or physical modification, this self-standing and lightweight (7.1 g m-2) fibrous mat showed 96.05% filtration efficiency for 3-5 µm NaCl particles, with a low pressure drop of only 18 Pa and high quality factor of 0.179 Pa-1 under an airflow velocity of 32 L min-1. By utilizing its photocatalytic attribute, the nanofibrous mat in situ eliminated the captured particles from incense burning under one Sun irradiation in 4 h, and thereby spontaneously regenerated in an easy manner. The straightforward grafting of Au nanoparticles onto nanofibers could enable a quick degradation toward cigarette smoke, mainly due to the photothermally elevated local temperature by Au around the reactive sites. The plasmonic fibrous mat kept a high and stable filtration efficiency of PM0.3, PM2.5, and PM10 over 98.62%, 99.76%, and 99.99% during an outdoor long-term filtration test for 12 h under sunlight irradiation (Nanjing, China, September, 26th, 2020, 7:30 to 19:30). This work provides a solution for solving the airborne pollution from its source, prolonging the lifetime of the filter, and avoiding the risk of producing secondary pollution.
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Peptides derived from crimson snapper scales (CSSPs) were reported to possess excellent free radical scavenging activities in vitro. In present study, the anti-aging and anti-oxidative stress effects of CSSPs were evaluated in Drosophila melanogaster models. Results showed that the addition of CSSPs in the diets of normal Drosophila could effectively extend their lifespan and improve the motor ability of aged Drosophila. Moreover, CSSPs could protect Drosophila from oxidative damage induced by H2O2, paraquat and UV irradiation. The extension of lifespan was found to be associated with the effects of CSSPs in improving the antioxidant defense system of Drosophila, manifesting as the reduction of oxidation products MDA and PCO, the elevated activities of T-SOD, CAT and GSH-Px, and the upregulated expression of antioxidant related genes after CSSPs supplemented. Furthermore, CSSPs at 6 mg/mL significantly downregulated mTOR signaling pathway and activated autophagy in aged male Drosophila, and the inhibition on mTOR activation was probably mediated by the antioxidant effects of CSSPs. Our findings suggest that CSSPs have the potential in making dietary supplements against natural aging and oxidative stress in organisms.
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Escamas de Animais/química , Antioxidantes/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Feminino , Peixes , Peróxido de Hidrogênio/toxicidade , Locomoção/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos da radiação , Paraquat/toxicidade , Transdução de Sinais/efeitos dos fármacos , Raios UltravioletaRESUMO
Plant growth-promoting rhizobacteria (PGPR) are a specific category of microbes that improve plant growth and promote greater tolerance to metal stress through their interactions with plant roots. We evaluated the effects of phytoremediation combining the cadmium accumulator Solanum nigrum L. and two Cd- and Pb-resistant bacteria isolates. To understand the interaction between PGPR and their host plant, we conducted greenhouse experiments with inoculation treatments at Nanjing Agricultural University (Jiangsu Province, China), in June 2018. Two Cd- and Pb-resistant PGPR with various growth-promoting properties were isolated from heavy metal-contaminated soil. 16S rRNA analyses indicated that the two isolates were Bacillus genus, and they were named QX8 and QX13. Pot experiments demonstrated that inoculation may improve the rhizosphere soil environment and promote absorption of Fe and P by plants. Inoculation with QX8 and QX13 also enhanced the dry weight of shoots (1.36- and 1.7-fold, respectively) and roots (1.42- and 1.96-fold) of plants growing in Cd- and Pb-contaminated soil, and significantly increased total Cd (1.28-1.81 fold) and Pb (1.08-1.55 fold) content in aerial organs, compared to non-inoculated controls. We also detected increases of 23% and 22% in the acid phosphatase activity of rhizosphere soils inoculated with QX8 and QX13, respectively. However, we did not detect significant differences between inoculated and non-inoculated treatments in Cd and Pb concentrations in plants and available Cd and Pb content in rhizosphere soils. We demonstrated that PGPR-assisted phytoremediation is a promising technique for remediating heavy metal-contaminated soils, with the potential to enhance phytoremediation efficiency and improve soil quality.
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Cádmio/análise , Chumbo/análise , Rhizobiaceae/metabolismo , Microbiologia do Solo , Poluentes do Solo/análise , Solanum nigrum/efeitos dos fármacos , Biodegradação Ambiental , Cádmio/metabolismo , China , Chumbo/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , RNA Ribossômico 16S , Rizosfera , Solo/química , Poluentes do Solo/metabolismo , Solanum nigrum/crescimento & desenvolvimento , Solanum nigrum/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Stroke at a young age is a societal challenge with a rising incidence. Our aim was to investigate sex differences in risk factors, etiology, and diagnostic process of ischemic stroke in Chinese young adults. METHODS: We retrospectively recruited 411 consecutive patients with first-ever ischemic stroke who were 18 to 50 years of age (mean age, 38.2 ± 8.1 years, women 31.4%), admitted to Peking Union Medical College Hospital from 2007 to 2018. Sex differences in demographics, risk factors, etiology, and diagnostic testing were analyzed. RESULTS: Females were significantly younger than males (36.9 versus 38.7 years, P<0.05). Hypertension (43.0%), smoking (41.1%), hyperlipidemia (37.2%), and hyperhomocysteinemia (27.9%) were common risk factors, statistically higher among males than females (P<0.05). Stroke etiology showed a significant sex difference that large-artery atherosclerosis and small-vessel diseases were more common among males than females (48.6% versus 19.4%, P<0.001; 9.9% versus 3.1%, P<0.05, respectively). Stroke of other determined etiology was more common among females (50.4% versus 19.1%, P<0.001). Relevant abnormality rates were higher among females on screening for autoimmune diseases and thrombophilia (23.3% versus 11.1%, P<0.05 and 50.0% versus 16.7%, P<0.001, respectively). CONCLUSIONS: A high rate of the traditional stroke risk factors and etiological subtype of large artery atherosclerosis in males were found, as well as prominent sex differences in relevant diagnostic testing abnormality rates, providing useful information for developing sex-specific strategies in stroke evaluation and prevention in young adults.
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Isquemia Encefálica/epidemiologia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Acidente Vascular Cerebral/epidemiologia , Adolescente , Adulto , Fatores Etários , Pequim/epidemiologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Adulto JovemRESUMO
BACKGROUND: Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. METHODS: We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. RESULTS: The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. CONCLUSION: Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.
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Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão Celular/genética , Neovascularização Patológica/tratamento farmacológico , Peptídeo Hidrolases/genética , Talidomida/farmacologia , Malformações Vasculares/tratamento farmacológico , Proteínas de Peixe-Zebra/genética , Inibidores da Angiogênese/farmacologia , Animais , Cicloeximida/toxicidade , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Regulação da Expressão Gênica , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/genética , Hemorragia/patologia , Humanos , Intestino Delgado/irrigação sanguínea , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Morfogênese/efeitos dos fármacos , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Malformações Vasculares/induzido quimicamente , Malformações Vasculares/genética , Malformações Vasculares/patologia , Peixe-ZebraRESUMO
Mammalian cells are extremely vulnerable to external assaults compared with plant and microbial cells because of the weakness of cell membranes compared with cell walls. Construction of ultrathin and robust artificial shells on mammalian cells with biocompatible materials is a promising strategy for protecting single cells against harsh environmental conditions. Herein, layer-by-layer assembly combined with a transglutaminase-catalyzed cross-linking reaction was employed to prepare cross-linked and biocompatible gelatin nanoshells on individual human cervical carcinoma cell line (HeLa) cells and mouse insulinoma cell line 6 (MIN6) cells. The encapsulated HeLa and MIN6 cells showed high viability and a prolonged encapsulation period. Moreover, the nanoshells can protect encapsulated cells from cytotoxic enzymes (such as trypsin) and polycation (polyethylenimine) attacks and help cells resist high physical stress. We also investigated how nanoshells would affect the cell viability, proliferation, and cell cycle distribution of encapsulated and released cells. The approach presented here may provide a new and versatile method for nanoencapsulation of individual mammalian cells, which would help cells endure various environmental stresses and thereby expand the application field of isolated mammalian cells.
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Nanoconchas , Materiais Biocompatíveis , Catálise , Gelatina , Humanos , TransglutaminasesRESUMO
BACKGROUND: Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). We found that levels of TRIM47 mRNA and protein were increased significantly in colorectal tumors compared with nontumor tissues and the increased levels were associated with advanced tumor stage and poor outcome. METHODS: We used quantitative polymerase chain reaction and western blot to measure levels of TRIM47 mRNA and protein in human colorectal cancer and paired normal tissues. TRIM47 was knocked down and overexpressed in colorectal cancer cells, and the effects on cell proliferation, migration and growth of xenograft tumors in nude mice were assessed. The signaling pathways were examined by western blot and immunoprecipitation assays. RESULTS: TRIM47 promoted CRC proliferation and metastasis in vitro and in vivo as an oncogene. Mechanistically, TRIM47 interacted physically with SMAD4, increasing its ubiquitination and degradation. Loss of SMAD4 leaded to up-regulation of CCL15 expression and caused growth and invasion in human CRC cells through the CCL15-CCR1 signaling. Moreover, TRIM47 overexpression played a role in CRC chemoresistance in response to 5-FU therapy. CONCLUSIONS: Our study demonstrated a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggested a potential target for CRC therapy.
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Proteínas de Transporte/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteína Smad4/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteínas Nucleares/metabolismo , Prognóstico , Proteólise , Carga Tumoral , UbiquitinaçãoRESUMO
BACKGROUND: Respiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections. METHODS: Nasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae). RESULTS: Among the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis. CONCLUSIONS: FilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs.
Assuntos
Infecções Bacterianas , Infecções Respiratórias , Viroses , Adolescente , Bactérias/genética , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Criança , Pré-Escolar , China/epidemiologia , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Viroses/diagnóstico , Viroses/epidemiologia , Viroses/microbiologia , Viroses/virologia , Vírus/genéticaRESUMO
BACKGROUND: Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis. METHODS: Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage. RESULTS: A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, Pâ¯<â¯0.001; external: 0.715; 95% CI, 0.674 to 0.756 vs. 0.648; 95% CI, 0.602 to 0.693, Pâ¯<â¯0.001). Also, the nomogram showed good calibration in internal and external validation and larger net benefit than TNM staging. CONCLUSION: We modified current N staging into a 4-level staging system based on the number of metastatic LNs: N0, no LN metastasis; N1, 1-2 metastatic LNs; N2, 3-8 metastatic LNs, and N3, >8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients.
Assuntos
Adenocarcinoma/patologia , Metástase Linfática , Prognóstico , Adenocarcinoma/classificação , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND: This was a cross-sectional survey to investigate the relationship of age, parent education, sleep duration, physical activity, and dietary habits with overweight or obesity in school-age children in Shanghai. METHODS: The survey gathered information from 13,001 children in grades 1 through 5 (age 6 to 10 years) among 26 elementary schools in 7 districts. Activity level was evaluated using the International Children's Leisure Activities Study Survey Questionnaire (CLASS-C). The definitions of normal, overweight, and obese were adjusted for each age. RESULTS: Logistic regression analysis indicated that age, being male, having ≤10 hours of sleep on non-school days, eating ≥1 vegetable/day, or drinking ≥1 sugar-sweetened drink/day increased the risk for a child being overweight or obese compared with having >10 hours of sleep or ≤3 vegetables or ≤3 sugar-sweetened drinks/month (p ≤ .008). Having >2 hours of outdoor activities on non-school days reduced the risk of being overweight or obese compared with ≤2 hours of outdoor activities on non-school days (p < .001). CONCLUSIONS: We found that age, sex, sleep, and some dietary habits impacted weight, and suggests that specific cultural and economic factors may impact risk of a child being overweight or obese.
Assuntos
Dieta/estatística & dados numéricos , Exercício Físico , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Sono , Fatores Etários , Bebidas , Índice de Massa Corporal , Peso Corporal , Criança , China/epidemiologia , Estudos Transversais , Comportamento Alimentar , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Modelos Logísticos , Masculino , Fatores Sexuais , Fatores Socioeconômicos , VerdurasRESUMO
Filtration surgery is currently being acknowledged as the most effective therapeutic modality for glaucoma; however, excessive scarring of a filtering bleb often leads to surgical failure. Subconjunctival administration of drug delivery systems provides a localized and sustained delivery of antifibrotic drugs to inhibit post-operative scarring. In this study, a long-acting delivery system of Cyclosporine A (CsA) was developed using thermogelling poly-(dl-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly-(dl-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers as the carrier. The drug could be easily entrapped into the polymer aqueous solution by simply mixing them at room temperature, and the prepared formulation was spontaneously transformed into an in situ thermogel loaded with drugs at body temperature. The formulation exhibited a sustained in vitro release of CsA from the thermogel over 2 months. The in vivo efficacy of subconjunctival administration of the CsA-loaded hydrogel system in inhibiting filtering bleb scarring was evaluated on a rabbit model of filtration surgery. No ocular tissue abnormalities and damage were observed. Compared with a local administration of the popular Mitomycin C solution at the surgery site, the CsA-loaded thermogel system remarkably inhibited scar formation, maintained stable low intraocular pressure and promoted filtering bleb survival for more than 10 weeks. This feature was attributed to both the anti-adhesion nature of the thermogel matrix and the antifibrotic effect of the sustainedly released CsA. These results suggest that the injectable PLGA-PEG-PLGA thermogel is a biocompatible carrier for sustained subconjunctival drug delivery, and the CsA-loaded hydrogel formulation has great potential for ocular antifibrotic therapy after glaucoma filtration surgery and others.
RESUMO
A highly sensitive and label-free amperometric immunosensor has been developed for the detection of carcinoembryonic antigen (CEA) based on layer-by-layer (LBL) assembly of gold nanoparticles (GNPs), multi-walled carbon nanotubes-thionine (MWNTs-THI) and chitosan (CHIT) on 3-mercaptopropanesulfonic, sodium salt (MPS)-modified gold electrode surface by electrostatic adsorption. The stepwise LBL assembly process of electroactive species on electrode surface was characterized by means of cyclic voltammetry (CV) in PBS. The factors influencing the performance of the resulting immunosensor were studied in detail. The morphologies of MWNTs, MWNTs-THI and GNPs-MWNTs-THI-CHIT were further characterized by transmission electron microscopy (TEM). The immunosensor was highly sensitive to CEA with a detection limit of 0.01 ng mL(-1) (signal/noise ratio of 3) and the linear range with two concentration intermittences was from 0.5 to 15.0 ng mL(-1) and from 15.0 to 200.0 ng mL(-1), respectively. In addition, the prepared immunosensor could be regenerated 10 times with 5 M urea solution. When the immunosensor was stored at 4 degrees C and measured intermittently (every 4-6 days), no apparent change was found over 3 months. The immunosensor system showed an excellent reproducibility and stability.