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1.
Clin Immunol ; 261: 110167, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38453127

RESUMO

Excessive inflammatory response and increased oxidative stress play an essential role in the pathophysiology of ischemia/reperfusion (I/R)-induced acute kidney injury (IRI-AKI). Emerging evidence suggests that lipoxin A4 (LXA4), as an endogenous negative regulator in inflammation, can ameliorate several I/R injuries. However, the mechanisms and effects of LXA4 on IRI-AKI remain unknown. In this study, A bilateral renal I/R mouse model was used to evaluate the role of LXA4 in wild-type, IRG1 knockout, and IRAK-M knockout mice. Our results showed that LXA4, as well as 5-LOX and ALXR, were quickly induced, and subsequently decreased by renal I/R. LXA4 pretreatment improved renal I/R-induced renal function impairment and renal damage and inhibited inflammatory responses and oxidative stresses in mice kidneys. Notably, LXA4 inhibited I/R-induced the activation of TLR4 signal pathway including decreased phosphorylation of TAK1, p36, and p65, but did not affect TLR4 and p-IRAK-1. The analysis of transcriptomic sequencing data and immunoblotting suggested that innate immune signal molecules interleukin-1 receptor-associated kinase-M (IRAK-M) and immunoresponsive gene 1 (IRG1) might be the key targets of LXA4. Further, the knockout of IRG1 or IRAK-M abolished the beneficial effects of LXA4 on IRI-AKI. In addition, IRG1 deficiency reversed the up-regulation of IRAK-M by LXA4, while IRAK-M knockout had no impact on the IRG1 expression, indicating that IRAK-M is a downstream molecule of IRG1. Mechanistically, we found that LXA4-promoted IRG1-itaconate not only enhanced Nrf2 activation and increased HO-1 and NQO1, but also upregulated IRAK-M, which interacted with TRAF6 by competing with IRAK-1, resulting in deactivation of TLR4 downstream signal in IRI-AKI. These data suggested that LXA4 protected against IRI-AKI via promoting IRG1/Itaconate-Nrf2 and IRAK-M-TRAF6 signaling pathways, providing the rationale for a novel strategy for preventing and treating IRI-AKI.


Assuntos
Injúria Renal Aguda , Lipoxinas , Traumatismo por Reperfusão , Succinatos , Camundongos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Quinases Associadas a Receptores de Interleucina-1/genética , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Quinases Associadas a Receptores de Interleucina-1/farmacologia , Transdução de Sinais , Rim/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/prevenção & controle
2.
Br J Nutr ; 131(11): 1852-1859, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38356387

RESUMO

Obesity is an important characteristic manifestation of metabolic syndrome (MetS), and body roundness index (BRI) is one of the anthropometric indicators associated with obesity. However, studies on the relationship between BRI and MetS risk are limited. We aimed to explore the relationship between baseline BRI and MetS in the USA population. Our study used data from the National Health and Nutrition Examination Survey from 1999 to 2018, ultimately enrolling and analysing 47 303 participants. Data-driven tertiles were used to categorise BRI levels, and multivariate logistic regression models were fitted to investigate the association of BRI with MetS in adults. In addition, receiver operating characteristic curve analysis was used to assess the ability of BRI to predict MetS. The distribution of BRI was different across ethnic groups with a gradual decrease in the proportion of non-Hispanic Whites and other races. In addition, BRI was significantly associated with traditional cardiovascular risk factors. Univariate regression analysis indicated BRI to be a moderate risk factor for MetS, and multivariate logistic regression analysis found that BRI remained an independent risk factor for MetS. After adjusting for confounding variables, a non-linear relationship was found between BRI levels and the prevalence of MetS. More importantly, BRI predicted MetS with the largest AUC among anthropometric measures. In summary, elevated baseline BRI levels are independently associated with the development of MetS, and baseline BRI may assist in identifying patients at risk for MetS, leading to early and optimal treatment to improve their outcomes.


Assuntos
Síndrome Metabólica , Inquéritos Nutricionais , Humanos , Síndrome Metabólica/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Fatores de Risco , Obesidade/epidemiologia , Prevalência , Índice de Massa Corporal
3.
Clin Exp Pharmacol Physiol ; 51(6): e13855, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636942

RESUMO

Cardiac microvascular endothelial cells (CMECs) are important cells surrounding the cardiomyocytes in the heart that maintain microenvironment homeostasis. Salvianic acid A sodium (SAAS) has been reported to prevent myocardial infarction (MI) injury. However, the role of SAAS on CMEC proliferation remains unclear. CEMCs exposed to oxygen glucose deprivation (OGD) were used to explore the angiogenic abilities of SAAS. In vivo, C57BL/6 mice were divided into three groups: sham, MI and SAAS + MI groups. Compared to OGD group, SAAS led to a reduction in the apoptotic rate and an increase of the proliferation in vitro. Additionally, SAAS increased the protein levels of Bcl2, HIF-1α and vascular endothelial growth factor (VEGF) with the reduction of Bax. In terms of the specific mechanisms, SAAS might inhibit HIF-1α ubiquitination and enhance the HIF-1α/VEGF signalling pathway to increase CMEC proliferation. Furthermore, SAAS increased the density of vessels, inhibited myocardial fibrosis and improved cardiac dysfunction in vivo. The present study has revealed that SAAS could potentially be used as an active substance to facilitate CMEC proliferation post-MI.


Assuntos
Lactatos , Infarto do Miocárdio , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Células Endoteliais/metabolismo , Sódio/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proliferação de Células , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
4.
IUBMB Life ; 75(3): 207-224, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34928543

RESUMO

It has been reported that B-cell CLL-lymphoma 10 (BCL10) serves as an oncogene in cervical cancer. However, the roles of BCL10 in hepatocellular carcinoma (HCC), especially involved in immune infiltration remain not clear. This study aims to explore the relationship between BCL10 and the prognosis and clinical significance, and immune infiltration in HCC. The expression of BCL10 was analyzed between HCC samples and non-tumor samples in the multiple datasets. In addition, the prognostic values of BCL10 and its methylation in HCC were also investigated. The clinical significance of BCL10 has also been explored. Furthermore, the correlation between BCL10 and immune infiltration in HCC microenvironment was assessed. Finally, the biological behaviors of BCL10 in HCC were verified by cell function experiments. It was found that the expression levels of BCL10 were increased in HCC patients in multiple datasets. Moreover, the increased BCL10 and its reduced methylation were associated with the poor survival. BCL10 was significantly associated with immune infiltration. When BCL10 was knocked down in HCC cells, their proliferation ability was significantly inhibited, their migration was significantly decreased, their apoptosis was significantly increased, and AKT signaling pathway was inhibited. In conclusion, BCL10 is a potential prognostic and diagnostic biomarker related to immune infiltration in HCC microenvironment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Microambiente Tumoral , Oncogenes , Apoptose , Biomarcadores Tumorais , Proteína 10 de Linfoma CCL de Células B
5.
Biomacromolecules ; 24(3): 1287-1298, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36745900

RESUMO

Ion conductive hydrogels (ICHs) have attracted great interest in the application of ionic skin because of their superior characteristics. However, it remains a challenge for ICHs to achieve balanced properties of high strength, large fracture strain, self-healing and freezing tolerance. In this study, a strong, stretchable, self-healing and antifreezing ICH was demonstrated by rationally designing a multiphysically cross-linked network structure consisting of the hydrophobic association, metal-ion coordination and chain entanglement among poly(acrylic acid) (PAA) polymer chains. The deliberately designed Brij S 100 acrylate (Brij-100A) micelle cross-linker can effectively dissipate energy and endow hydrogels with desirable stretchability. The self-healing ability of hydrogels originates from the reversible hydrophobic association in micelles and Fe3+-COO- coordination. After the addition of NaCl, the chain-entangled physical network caused by the salting-out effect can both enhance mechanical strength and promote electron transport. With the synergy of hydrophobic association, mental-ligand coordination and chain entanglement, the PAA/Brij-100A/Fe3+/NaCl (PAA/BA/Fe3+/NaCl) hydrogels exhibited a high tensile strain of 1140%, a tensile strength of 0.93 MPa and a toughness of 3.48 MJ m-3. Besides, the PAA/BA/Fe3+/NaCl hydrogels exhibited a high conductivity of 0.43 S m-1 and good freezing resistance. The ionic skin based on the PAA/BA/Fe3+/NaCl hydrogels showed high sensitivity (GF = 5.29), wide strain range (0-950%), fast response time (220 ms) and good stability. Also, the self-healing ability of the ionic skin can significantly prolong its service time, and the antifreezing property can broaden its applicable temperature. This study offers new insight into the design of multifunctional ionic skin for wearable electronics.


Assuntos
Hidrogéis , Cloreto de Sódio , Pele , Acrilatos , Condutividade Elétrica , Íons , Micelas
6.
J Environ Sci (China) ; 127: 541-551, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36522084

RESUMO

A typical anthropogenically disturbed urban river polluted by a combination of conventional pollutants (nitrogen and phosphorus pollution) and heavy metals was investigated along a 238 km stretch. Changes in the bacterial community were evaluated using high-throughput sequencing, and the relationships between bacteria, heavy metals, and conventional pollutants were investigated. There was large spatial heterogeneity in the bacterial community along the river, and bacterial diversity in the upstream and midstream sections was much higher than in the downstream section. Heavy metals and conventional pollutants both exhibited close correlations with bacterial diversity and composition. For instance, potential fecal indicator bacteria, sewage indicator bacteria and pathogenic bacteria, such as Ruminococcus and Pseudomonas, were closely associated with Cu, Zn, and NH4+-N. Rather than conventional pollutants, heavy metals were the main driving factors of the microbial community characteristics. These results confirm that bacterial communities play a crucial role in biogeochemical cycles. Therefore, heavy metals could be used as biomarkers of complex pollution to indicate the pollution status of riverine ecosystems and contribute to the restoration of habitats in anthropogenically disturbed urban rivers.


Assuntos
Poluentes Ambientais , Metais Pesados , Microbiota , Poluentes Químicos da Água , Sedimentos Geológicos/microbiologia , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Bactérias , China
7.
Lipids Health Dis ; 21(1): 111, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307819

RESUMO

BACKGROUND: Lipid-lowering therapy is important, and the distribution of lipid levels and the incidence of hyperlipidemia may vary in different subgroups of the population. We aimed to explore the distribution of lipid levels and the prevalence of hyperlipidemia in subpopulations with subgroup factors, including age, sex, race, and smoking status. METHODS: Our study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, ultimately enrolling and analyzing 15,499 participants. A cross-sectional analysis was performed to assess the distribution of lipids and prevalence of hyperlipidemia in subpopulations, and multifactorial logistic regression analyses were performed for the prevalence of hyperlipidemia, adjusted for age, sex, race and smoking status. RESULTS: Blacks had significantly lower mean serum total cholesterol and triglycerides and higher serum high-density lipoprotein cholesterol (HDL-C) than whites (P < 0.001). In contrast, Mexican Americans had markedly higher mean serum triglycerides and lower serum HDL-C than whites (P < 0.001). Furthermore, the prevalence of hypercholesterolemia and hypertriglyceridemia was lower in blacks than in whites (P = 0.003 and P < 0.001, respectively), while the prevalence of hypertriglyceridemia was significantly higher in Mexican Americans than in whites (P = 0.002). In addition, total cholesterol and triglyceride levels were significantly higher in women aged 65 years or older and markedly higher than in men in the same age group (P < 0.001). In addition, overall mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels were higher in smokers than in nonsmokers (P = 0.01, P < 0.001, and P = 0.005, respectively). CONCLUSION: Based on NHANES data, the mean lipid levels and prevalence of hyperlipidemia differed by sex, age, race, and smoking status.


Assuntos
Hiperlipidemias , Hipertrigliceridemia , Masculino , Feminino , Humanos , Hiperlipidemias/epidemiologia , Inquéritos Nutricionais , Prevalência , Estudos Transversais , HDL-Colesterol , Triglicerídeos , Hipertrigliceridemia/epidemiologia
8.
Thorac Cardiovasc Surg ; 70(6): 475-481, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35785810

RESUMO

BACKGROUND: Tricuspid regurgitation (TR) is common and related to poor prognosis in patients after left ventricular assist device (LVAD) implantation. The concomitant tricuspid valve surgery (TVS) at the time of LVAD implantation on short and long-term outcomes are controversial in current evidence. METHODS: This is a single-center, observational, retrospective study. We enrolled patients with moderate-to-severe TR who received LVAD implantations from 2009 to 2020. Postoperative right ventricular failure (RVF), right ventricular assist device (RVAD) use, hospital mortality, new-onset renal replacement therapy (RRT), and acute kidney injury (AKI) were evaluated retrospectively. RESULTS: Sixty-eight patients were included, 36 with and 32 without concomitant TVS. Baseline characteristics did not differ between the two groups. Patients receiving TVS had significantly increased incidences of postoperative RVF (52.8 vs. 25.0%, p = 0.019), RVAD implantation (41.7 vs. 18.8%, p = 0.041), and new-onset RRT (22.2 vs. 0%, p = 0.004). No difference in the incidence of AKI and hospital mortality was detected. Besides, these associations remained consistent in patients who underwent LVAD implantation via median sternotomy. During a median follow-up of 2.76 years, Kaplan-Meier analysis and competing-risk analysis showed that TVS was not associated with better overall survival in patients after LVAD implantation compared with the no-TVS group. CONCLUSION: Our study suggests that concomitant TVS failed to show benefits in patients receiving LVAD implantation. Even worse, concomitant TVS is associated with significantly increased incidences of RVF, RVAD use, and new-onset of RRT. Considering the small sample size and short follow-up, these findings warrant further study.


Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Coração Auxiliar , Insuficiência da Valva Tricúspide , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Coração Auxiliar/efeitos adversos , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgia
9.
Bull Environ Contam Toxicol ; 109(5): 691-697, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35715700

RESUMO

Human activities can introduce heavy metals to water bodies, where they are then deposited in sediments. The risks, spatial distributions, and toxicities of heavy metals in sediment were investigated along the North Canal in the densely Beijing-Tianjin area. The average geoaccumulation index ranged from 0.2 to 2.91 and the highest value was obtained for Cd. All the pollution load indexes were greater than one, indicating that the heavy metals originated from anthropogenic sources. The risk indexes at three sampling points were greater than 300, indicating high potential ecological risk. Two probable effect concentration quotient values greater than 0.5, suggesting potential toxicity to certain sediment-dwelling organisms. Identification and evalution heavy metals could assist in improvement of the water quality, and support management strategies to restore the environment.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Humanos , Rios , Sedimentos Geológicos , Monitoramento Ambiental , Pequim , Poluentes Químicos da Água/análise , Medição de Risco , Metais Pesados/análise , Qualidade da Água , China
10.
Mol Biol Rep ; 47(12): 9479-9488, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33210255

RESUMO

Advanced glycation end products (AGEs) are a group of modified proteins and/or lipids with damaging potential. AGEs-RAGE pathway plays a critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced AGEs receptor (RAGE) in the aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin (ATV) on inflammation and oxidation stress in the cerebral cortex were investigated, and the underlying mechanisms were explored. Apolipoprotein E (ApoE)-/- male mice were divided into four groups: control, AGEs, AGEs + ALT711 (Alagebrium chloride) and AGEs + ATV. ß-amyloid (Aß) formation in the cerebral cortex was assessed through Congo red staining and the functional state of neurons was evaluated by Nissl's staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, Nuclear factor kappa B (NF-κB) p65 and Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) p47phox were detected by real-time polymerase chain reaction (PCR) and western blot. There were significant increases in AGEs deposit, Aß formation, and the expressions of RAGE, NF-κB p65, and NADPH oxidase p47phox, and a decrease Nissl body in AGEs group compared with control group. ALT711 group recovered above change compared with AGEs group. Atorvastatin reduced Aß formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGEs deposit and RAGE expressions. Atorvastatin alleviates AGEs-induced neuronal impairment by alleviating inflammation and oxidative stress via inhibiting NADPH oxidase-NF-κB pathway.


Assuntos
Peptídeos beta-Amiloides/genética , Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Córtex Cerebral/efeitos dos fármacos , NADPH Oxidases/genética , Fator de Transcrição RelA/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/genética , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Imuno-Histoquímica , Inflamação , Masculino , Camundongos , Camundongos Knockout , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais , Tiazóis/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo
12.
Brain Res ; 1824: 148684, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37992795

RESUMO

Spinal cord injury (SCI) is a serious traumatic disease with no effective treatment. This study aimed to explore the therapeutic effect of syringaresinol on SCI. First, the potential targets and associated signaling pathways of syringaresinol were predicted by bioinformatics analysis and molecular docking. Second, MTT was employed to evaluate cell proliferation rate, Western blot was performed to detect protein expression, RT-qPCR was conducted to detect mRNA expression levels, flow cytometry and 5-ethynyl-2'-deoxyuridine (EDU) staining were used to determine cell apoptosis, and immunofluorescence and immunohistochemistry were used to estimate the expression of RNA binding fox-1 homolog 3 and clipped caspase 3. Basso-Beattie-Bresnahan scores and inclined plate tests were conducted to analyze hindlimb locomotor function. Results showed that syringaresinol could inhibit the apoptosis of glutamate-treated SHSY5Y cells by upregulating the expression of ubiquitination factor E4B (UBE4B) and activating the AKT serine/threonine kinase (AKT) signaling pathway. This effect can be rescued by UBE4B knockdown or AKT pathway inhibition. Syringaresinol remarkably improved locomotor function and increased neuronal survival in SCI rats. Our results suggested that syringaresinol could promote locomotor functional recovery by reducing neuronal apoptosis by activating the UBE4B/AKT signaling pathway.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Traumatismos da Medula Espinal , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Medula Espinal/metabolismo , Ratos Sprague-Dawley , Simulação de Acoplamento Molecular , Transdução de Sinais , Traumatismos da Medula Espinal/metabolismo , Apoptose , Neurônios/metabolismo , Ubiquitinação , Serina/metabolismo , Recuperação de Função Fisiológica
13.
ESC Heart Fail ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831637

RESUMO

AIMS: Left ventricular assist device (LVAD) implantation, a therapy for end-stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation. METHODS AND RESULTS: Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long-term outcomes were analysed. The primary outcome was long-term mortality. A total of 19 517 patients who received the first continuous-flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P = 0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P < 0.001) pre-implant PLT counts were associated with an increased risk of 2 year mortality. Compared with intermediate, a high post-implant PLT count was associated with an increased risk of 4 year mortality (HR, 1.38, 95% CI: 1.26 to 1.52, P < 0.001). Besides, both pre- and post-implant PLT counts exhibit a U-shaped association with the risk of mortality. CONCLUSIONS: LVAD implantation could improve the PLT count towards normalization. Abnormal pre-/post-implant PLT counts were independently associated with increased risks of long-term mortality.

14.
ESC Heart Fail ; 11(1): 271-281, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37967837

RESUMO

AIMS: Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. METHODS AND RESULTS: This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5-51.7% vs. 51.1%, 95% CI: 45.3-56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91-1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95-1.22, P = 0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87-1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94-1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. CONCLUSIONS: In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Nefropatias , Adulto , Humanos , Coração Auxiliar/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Retrospectivos
15.
J Immunol Res ; 2023: 1116841, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663051

RESUMO

Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-α and IL-1ß, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-κB) signaling pathway in APAP-administered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-κB signaling in mice.


Assuntos
Proteína HMGB1 , NF-kappa B , Animais , Camundongos , Acetaminofen/efeitos adversos , Receptor 4 Toll-Like , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Proteína HMGB1/genética , Fígado , Estresse Oxidativo
16.
J Heart Lung Transplant ; 42(9): 1261-1274, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37127070

RESUMO

BACKGROUND: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking. OBJECTIVES: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients. METHODS: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe). RESULTS: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (ß, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (ß, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances. CONCLUSIONS: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis.


Assuntos
Anemia , Insuficiência Cardíaca , Coração Auxiliar , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Coração Auxiliar/efeitos adversos , Qualidade de Vida , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Sistema de Registros , Anemia/complicações , Anemia/epidemiologia , Hemoglobinas , Estudos Retrospectivos , Resultado do Tratamento
17.
Sci Total Environ ; 815: 152570, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34954165

RESUMO

Organic matter (OM) is an important component of riverine environments and a major factor in the migration and transformation of hydrophobic organic substances, such as polycyclic aromatic hydrocarbons (PAHs), to sediments. We studied the distributions, sources, and correlations between PAHs and OM in sediments from the Duliujian and the Beiyun rivers in North China. Sixteen PAHs were detected in the surface sediments at total concentrations ranging from 356 to 4652 ng·g-1 dry weight, which caused a moderate to high level of pollution. The PAH distributions were significantly and positively correlated with OM (p < 0.01) and higher concentrations were detected downstream of areas affected by human activity. Petroleum, coal, and wood combustion were the main sources of PAHs in riverine sediments, and the sources of OM in sediment included terrestrial and aquatic higher plants, soil, and sewage discharge. The OM accumulated and aged along the river, with increases in the degree of aromaticity and condensation, which led to stronger adsorption of PAHs. Our results will help to promote the management and restoration of contaminated riverine sediments.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Idoso , China , Monitoramento Ambiental , Sedimentos Geológicos , Atividades Humanas , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise
18.
Nanomaterials (Basel) ; 12(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35745461

RESUMO

Designing and modifying nanoporous metal foils to make them suitable for supercapacitor and catalysis is significant but challenging. In this work, CuxO nanoflakes have been successfully in situ grown on nanoporous Cu foil via a facile electrooxidation method. A Ga-assisted surface Ga-Cu alloying-dealloying is adopted to realize the formation of a nanoporous Cu layer on the flexible Cu foil. The following electrooxidation, at a constant potential, modifies the nanoporous Cu layer with CuxO nanoflakes. The optimum CuxO/Cu electrode (O-Cu-2h) delivers the maximum areal capacitance of 0.745 F cm-2 (410.27 F g-1) at 0.2 mA cm-2 and maintains 94.71% of the capacitance after 12,000 cycles. The supercapacitor consisted of the O-Cu-2h as the positive electrode and activated carbon as the negative electrode has an energy density of 24.20 Wh kg-1 and power density of 0.65 kW kg-1. The potential of using the electrode as oxygen evolution reaction catalysts is also investigated. The overpotential of O-Cu-2h at 10 mA cm-2 is 394 mV; however, the long-term stability still needs further improvement.

19.
Front Pharmacol ; 13: 902102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865965

RESUMO

Osteoporosis (OP) is an aging-related disease that is the main etiology of fragility fracture. Qing'e Pill (QEP) is a mixture of traditional Chinese medicine (TCM) consisting of Eucommia ulmoides Oliv., Psoralea corylifolia L., Juglans regia L., and Allium sativum L. QEP has an anti-osteoporosis function, but the underlying mechanism remains unclear. In this study, online databases were employed to determine the chemical compounds of QEP and potential target genes in osteoporosis. Potential pathways associated with genes were defined by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. A compound-target-disease network was constructed. Hub genes screened through Cytoscape were intersected with the FerrDB database. The potential key genes were validated in HFOB 1.19 cells, and rat models were ovariectomized through Western blot, RT-qPCR, ELISA, HE staining, immunohistochemistry, and immunofluorescence analyses. The intersection targets of QEP and osteoporosis contained 121 proteins, whereas the target-pathway network included 156 pathways. We filtered five genes that stood out in the network analysis for experimental verification. The experiments validated that QEP exerted therapeutic effects on osteoporosis by inhibiting ferroptosis and promoting cell survival via the PI3K/AKT pathway and ATM. In conclusion, combining the application of network analysis and experimental verification may provide an efficient method to validate the molecular mechanism of QEP on osteoporosis.

20.
Environ Sci Pollut Res Int ; 29(31): 46649-46664, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35171423

RESUMO

Suspended particulate matter (SPM) is a major source of contamination in urban rivers as it serves as a carrier for pollutants, such as heavy metals. In this study, the Beiyun River, northern China, was used as a case study to determine the characteristics of SPM-associated heavy metal spatial distribution, to evaluate the potential ecological risks and identify heavy metal sources. The concentrations of seven heavy metals and other associated indicators (TC, TN, TP, and OM) were measured at 12 sites and analyzed by Pearson correlation (PC) and principal component analyses (PCA). The average concentrations of Cr, Ni, Cu, Zn, As, Cd, and Pb were 70.72, 27.88, 31.35, 115.70, 27.77, 0.23, and 29.62 mg/kg, respectively, with significant spatial differences occurring between some elements. Igeo values established the ranked order of heavy metal pollutant concentrations in SPM as As > Cd > Zn > Cu > Pb > Cr > Ni. [Formula: see text] analysis demonstrated that the ranked order of potential ecological risk from the seven metals was Cd > As > Cu > Pb > Ni > Cr > Zn. Potential ecological risk index (RI) results confirmed the high potential ecological risk in the study area. Among the measured heavy metals, Cd represented the highest pollution risk, as shown by its highest [Formula: see text] value. Correlation analysis (CA) showed that Zn had a strong correlation with Cu and Pb. Significant positive correlations were found between TC, TN, TP, and Cu. Three element pairs, Zn-Cd, Cr-Cu, and Cr-Ni, were also found to have strong correlations. Zn, Cu, and Ni were mainly introduced by human activities including urban industrial sewage discharge (such as metallurgy and electroplating industrial wastewater), agricultural drainage, and landfill wastewater, while Cr mainly originated from natural processes like mineral weathering and atmospheric precipitation. This information on the concentration, risk, and sources of SPM in Beiyun River provides an important reference for the reduction of heavy metal pollution in SPM in a typical river in the Haihe River Basin (China).


Assuntos
Metais Pesados , Poluentes Químicos da Água , Cádmio/análise , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Humanos , Chumbo/análise , Metais Pesados/análise , Material Particulado/análise , Medição de Risco , Rios , Águas Residuárias/análise , Poluentes Químicos da Água/análise
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