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1.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38815582

RESUMO

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.


Assuntos
Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38446716

RESUMO

OBJECTIVES: The present study aims to explore the application value of the air bronchogram (AB) sign and other computed tomography (CT) signs in the early diagnosis of lung adenocarcinoma (LUAD). METHOD: The pathological information and CT images of 130 patients diagnosed with N0 and M0 solitary pulmonary nodules (diameter ≤3 cm) and treated with surgical resection in our hospital between June 2021 and June 2022 were analyzed. RESULTS: The patients were divided into the benign pulmonary nodule (BPN) group (14 cases), the AIS group (30 cases), the MIA group (10 cases), and the IAC group (76 cases). Among the 116 patients with AIS and LUAD, 96 showed an AB sign. Among the 14 patients with BPN, only 4 patients showed an AB sign. The average CT value and maximum diameter were significantly higher in the IAC group than in the AIS and MIA groups. In the BPN group, 5 patients had an average CT value of >80 HU. Among all LUAD-based groups, there was only 1 patient with a CT value of >60 HU. CONCLUSIONS: The identification of the AB sign based on CT imaging facilitates the differentiation between benign and malignant nodules. The CT value and maximum diameter of pulmonary adenocarcinoma nodules increase with the increase of the malignancy degree. The nodule type, CT value, and maximum diameter are useful for predicting the pathological type and prognosis. If the average CT value of pulmonary nodules is >80 HU, LUAD may be excluded.

3.
J Am Soc Nephrol ; 34(11): 1900-1913, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37787447

RESUMO

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.


Assuntos
Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Predisposição Genética para Doença , Glomerulonefrite por IGA/genética , Haptoglobinas/genética , Progressão da Doença , Polimorfismo de Nucleotídeo Único
4.
Immunity ; 40(4): 477-89, 2014 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-24745332

RESUMO

We identified three retinoid-related orphan receptor gamma t (RORγt)-specific inhibitors that suppress T helper 17 (Th17) cell responses, including Th17-cell-mediated autoimmune disease. We systemically characterized RORγt binding in the presence and absence of drugs with corresponding whole-genome transcriptome sequencing. RORγt acts as a direct activator of Th17 cell signature genes and a direct repressor of signature genes from other T cell lineages; its strongest transcriptional effects are on cis-regulatory sites containing the RORα binding motif. RORγt is central in a densely interconnected regulatory network that shapes the balance of T cell differentiation. Here, the three inhibitors modulated the RORγt-dependent transcriptional network to varying extents and through distinct mechanisms. Whereas one inhibitor displaced RORγt from its target loci, the other two inhibitors affected transcription predominantly without removing DNA binding. Our work illustrates the power of a system-scale analysis of transcriptional regulation to characterize potential therapeutic compounds that inhibit pathogenic Th17 cells and suppress autoimmunity.


Assuntos
Benzenoacetamidas/farmacologia , Compostos Benzidrílicos/farmacologia , Digoxina/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Redes Reguladoras de Genes/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Esclerose Múltipla/tratamento farmacológico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Subpopulações de Linfócitos T/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Androstenóis/química , Animais , Benzenoacetamidas/química , Compostos Benzidrílicos/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Linhagem da Célula/efeitos dos fármacos , Citocinas/metabolismo , Digoxina/química , Encefalomielite Autoimune Experimental/imunologia , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Fragmentos de Peptídeos/imunologia , Ligação Proteica/efeitos dos fármacos , Relação Estrutura-Atividade , Biologia de Sistemas , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos
5.
Environ Sci Technol ; 57(49): 20951-20961, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38009568

RESUMO

Biogenic sulfidation of zero-valent iron (ZVI) using sulfate reducing bacteria (SRB) has shown enhanced dechlorination rates comparable to those produced by chemical sulfidation. However, controlling and sustaining biogenic sulfidation to enhance in situ dechlorination are poorly understood. Detailed interactions between SRB and ZVI were examined for 4 months in column experiments under enhanced biogenic sulfidation conditions. SRB proliferation and changes in ZVI surface properties were characterized along the flow paths. The results show that ZVI can stimulate SRB activity by removing excessive free sulfide (S2-), in addition to lowering reduction potential. ZVI also hinders downgradient movement of SRB via electrostatic repulsion, restricting SRB presence near the upgradient interface. Dissolved organic carbon (e.g., >2.2 mM) was essential for intense biogenic sulfidation in ZVI columns. The presence of SRB in the upgradient zone appeared to promote the formation of iron polysulfides. Biogenic FeSx deposition increased the S content on ZVI surfaces ∼3-fold, corresponding to 3-fold and 2-fold improvements in the trichloroethylene degradation rate and electron efficiency in batch tests. Elucidation of SRB and ZVI interactions enhances sustained sulfidation in ZVI permeable reactive barrier.


Assuntos
Ferro , Poluentes Químicos da Água , Ferro/química , Poluentes Químicos da Água/química , Elétrons
6.
Kidney Blood Press Res ; 48(1): 436-444, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37062285

RESUMO

INTRODUCTION: A previous genome-wide association study has identified CARD9 (caspase recruitment domain family member 9) as a susceptibility gene for immunoglobulin A nephropathy (IgAN), which encodes an adapter protein and is related to mucosal immunity. This study aimed to investigate the association of CARD9 variants with the clinicopathological phenotypes and prognosis of IgAN. METHODS: Eight single nucleotide polymorphisms within CARD9 were genotyped using Sequenom MassARRAY iPLEX for 986 IgAN patients in this study. Logistic and linear regression analyses adjusted for age and gender were performed to evaluate the effects of CARD9 gene polymorphisms on clinicopathological phenotypes. The Kaplan-Meier method and Cox proportional hazard models were applied to analyze the associations between genetic variants and renal survival. RESULTS: The T allele of rs10747047 was strongly associated with higher levels of serum creatinine (p = 0.005) and lower levels of estimated glomerular filtration rate (p = 0.005). The rs10870149-G and rs10870077-C alleles were associated with elevated 24-h urine protein excretion (p = 0.041 and 0.022, respectively) and more serious segmental glomerulosclerosis lesions (p = 0.005 and 0.041, respectively) in IgAN patients. Carriers with the T allele of rs10781533 and the C allele of rs3812552 also presented with severe segmental glomerulosclerosis lesions (p = 0.001 and 0.010, respectively). Additionally, rs10747047-C and rs10870077-C alleles were independently related to the poor prognosis of IgAN patients after adjustments for covariates (TT vs. CC hazard ratio [HR] = 0.138, 95% confidence interval [95% CI] = 0.022-0.871, p = 0.035; GG vs. CC HR = 0.321, 95% CI = 0.123, 0.836, p = 0.020, respectively). CONCLUSION: CARD9 variants are associated with disease severity and rapid disease progression for IgAN in a Chinese Han population.


Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/patologia , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único/genética , Progressão da Doença , Proteínas Adaptadoras de Sinalização CARD/genética
7.
Bull Environ Contam Toxicol ; 111(1): 15, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37452857

RESUMO

To promote the reuse of remediated soil (RS) and facilitate the cleanup of rainwater in sponge city, we investigated the effects of ceramsite made from RS serving as urban street cushion. Ceramsite was prepared by RS or pollution-free soil (PS) and showed no difference in physical properties. Compared with gravel, ceramsite had purification effects on effluents, reducing the content of chemical oxygen demand, total nitrogen, and ammoniacal nitrogen. However, the content of total phosphorus and the concentration of Cr(VI) and arsenic slightly increased in ceramsite groups, inferring potential risk. Microbial community analysis proved that ceramsite promoted microbial growth and increased microbial diversity. A long-term risk assessment indicated that ceramsite was good at fixing heavy metals during leaching process. Taken together, ceramsite prepared from RS could serve as excellent urban street cushion with little potential risk to surroundings.


Assuntos
Metais Pesados , Solo , Metais Pesados/análise , Análise da Demanda Biológica de Oxigênio , Medição de Risco , Nitrogênio/análise
8.
J Org Chem ; 87(11): 7022-7032, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35583475

RESUMO

The regioselective synthetic approach to higher alkenes from lower alkenes by using sulfoxides as alkyl or aryl reagents in the Fe3+/H2O2 system has been developed. This reaction realized direct alkylation or arylation of alkenes. In this reaction, sulfoxides afforded one Csp3 or Csp2 atom to the C═C bond of alkenes; one new Csp2-Csp3 bond or Csp2-Csp2 bond was formed. Nearly 40 products including di-, tri-, and tetra-substituted products were regioselectively synthesized. Both aliphatic and aromatic alkenes could participate in this reaction. Moreover, not only dimethyl sulfoxide but also three other sulfoxides can be applied to this reaction, including diethyl, dibenzyl, and diphenyl sulfoxide. The mechanism studies showed that this reaction may experience a coupling process via radical addition-elimination and the Fe3+/H2O2 system made the sulfoxides offered one alkyl or aryl radical to the C═C bond of alkenes.

9.
Mediators Inflamm ; 2022: 6922809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405991

RESUMO

Background and Aims: Mean platelet volume to platelet count ratio (MPV/PC) has been found to be an independent risk factor for mortality in various diseases, including cardiovascular disease, cancer, and hemodialysis. We aimed to evaluate the association between MPV/PC and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods and Results: We conducted a retrospective cohort study at a single center and enrolled 1473 PD patients who were catheterized at our PD center from January 1, 2006, to December 31, 2013. All patients were divided into four groups according to the quartiles of baseline MPV/PC levels and followed up until December 31, 2018. A total of 453 patients died, and 221 deaths were caused by cardiovascular disease during a median follow-up time of 48.0 (21.9-82.2) months. There was a significant interaction by age of association between MPV/PC level and all-cause mortality (P = 0.009), and multivariate Cox regression analysis showed that higher MPV/PC level was related to a decreased risk of all-cause and CV mortality in PD patients aged < 60 years (HR = 0.62, 95%CI = 0.40 - 0.96, P = 0.032; HR = 0.49, 95%CI = 0.26 - 0.93, P = 0.029, respectively), rather than in patients aged ≥ 60 years (HR = 1.37, 95%CI = 0.84 - 2.22, P = 0.208; HR = 1.50, 95%CI = 0.77 - 2.92, P = 0.237, respectively). Conclusion: Our results indicated that low MPV/PC level was an independent risk factor for all-cause and CV mortality in PD patients aged less than 60 years.


Assuntos
Doenças Cardiovasculares , Diálise Peritoneal , Humanos , Volume Plaquetário Médio , Contagem de Plaquetas , Estudos Retrospectivos , Prognóstico
10.
Ren Fail ; 44(1): 1708-1716, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36259485

RESUMO

OBJECTIVE: End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients. METHOD: A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome. RESULT: A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13-15.65, p < 0.001), history of central nervous system disorder (OR = 3.03, 95% CI: 1.21-7.56, p = 0.018) and hypoalbuminemia (OR= 1.87, 95% CI: 1.01-3.47, p = 0.046) were independent factors associated with AAE in ESKD patients. After adjustment for confounders, AAE was associated with composite outcomes of in-hospital mortality and treatment withdrawal (OR = 4.36, 95% CI: 2.09-9.10, p < 0.001). CONCLUSION: The prevalence of AAE was 4.4% in ESKD patients and varied among different antibiotics. Anuria, history of central nervous system disorder and hypoalbuminemia were associated with AAE in ESKD patients. AAE is associated with worse outcomes in ESKD patients.


Assuntos
Anuria , Encefalopatias , Hipoalbuminemia , Falência Renal Crônica , Humanos , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Sistema de Registros , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Encefalopatias/induzido quimicamente , Encefalopatias/epidemiologia , Encefalopatias/complicações
11.
J Org Chem ; 86(19): 13446-13453, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546730

RESUMO

Two C═C bond participation in annulation to pyridines using N,N-dimethylformamide (DMF) as the N1 and C4 synthons has been carried out. In this reaction, DMF contributed one N atom and one C atom to two disconnected positions of pyridine ring, with no need for an additional nitrogen source. Two C═C bonds in two molecules of substituted styrenes offered four carbon atoms in the presence of iodine and persulfate. With the optimized conditions in hand, both symmetric and unsymmetric diaryl-substituted pyridines were obtained in useful yields. On the basis of relevant literature and a series of control experimental results, a possible mechanism was proposed in this work, which may demonstrate how DMF provides both N1 and C4 sources.

12.
Nutr Metab Cardiovasc Dis ; 31(7): 2081-2088, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34039506

RESUMO

BACKGROUND AND AIMS: Previous studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients. METHODS AND RESULTS: In this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6-71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06-1.93, P = 0.019), 1.54 (95%CI = 1.01-2.35, P = 0.046), respectively. CONCLUSION: Higher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.


Assuntos
HDL-Colesterol/sangue , Nefropatias/terapia , Monócitos , Diálise Peritoneal Ambulatorial Contínua/mortalidade , Adulto , Biomarcadores/sangue , Causas de Morte , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/mortalidade , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Nutr Metab Cardiovasc Dis ; 31(4): 1148-1155, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33618923

RESUMO

BACKGROUND AND AIMS: Iron deficiency is prevalent, but there is limited data about the relationship between iron status and poor outcomes in chronic kidney disease patients undergoing peritoneal dialysis (PD). We aimed to investigate the association between iron status and mortality in PD patients. METHODS AND RESULTS: This retrospective study was conducted on incident PD patients from January 2006 to December 2016 and followed up until December 2018. Patients were categorized into four groups according to baseline serum transferrin saturation (percent) and ferritin levels (ng/ml): reference (20-30%, 100-500 ng/ml), absolute iron deficiency (<20%, <100 ng/ml), function iron deficiency (FID) (<20%, >100 ng/ml), and high iron (>30%, >500 ng/ml). Among the 1173 patients, 77.5% had iron deficiency. During a median follow-up period of 43.7 months, compared with the reference group, the FID group was associated with increased risk for all-cause [adjusted hazard ratio (aHR) 1.87, 95% confidence interval (95% CI) 1.05-3.31, P = 0.032], but not cardiovascular (CV) mortality. Additionally, the high iron group had a more than four-fold increased risk of both all-cause and CV mortality [aHR 4.32 (95% CI 1.90-9.81), P < 0.001; aHR 4.41 (95% CI 1.47-13.27), P = 0.008; respectively]. CONCLUSION: FID and high iron predict worse prognosis of patients on PD.


Assuntos
Distúrbios do Metabolismo do Ferro/sangue , Ferro/sangue , Nefropatias/terapia , Diálise Peritoneal/mortalidade , Adulto , Biomarcadores/sangue , China/epidemiologia , Feminino , Ferritinas/sangue , Humanos , Deficiências de Ferro , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/mortalidade , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Transferrina/metabolismo , Resultado do Tratamento
14.
Blood Purif ; 50(6): 837-847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596582

RESUMO

BACKGROUND: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. METHODS: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. RESULTS: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8-61.0) µM. During a median follow-up of 63.7 months (IQR, 43.9-87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01-1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07-1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02-1.94; p = 0.038) in men but not in women. CONCLUSIONS: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.


Assuntos
Metilaminas/sangue , Diálise Peritoneal/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
15.
J Clin Lab Anal ; : e23995, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498313

RESUMO

BACKGROUND: Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes. METHODS: Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated. RESULTS: Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders. CONCLUSIONS: Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.

16.
J Am Soc Nephrol ; 31(12): 2949-2963, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32912934

RESUMO

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.


Assuntos
Povo Asiático/genética , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Glomerulonefrite por IGA/genética , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Estudo de Associação Genômica Ampla , Humanos , Fatores Reguladores de Interferon/genética , Masculino , Pessoa de Meia-Idade , Proteína-Arginina Desiminase do Tipo 4/genética , Receptores Imunológicos/genética
17.
Ren Fail ; 43(1): 159-167, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33441045

RESUMO

BACKGROUND: In the first year of dialysis, patients are vulnerable to cardiovascular disease (CVD) hospitalization, but knowledge regarding the risk factors and long-term outcomes of cardiovascular readmission within the first year after dialysis in incident continuous ambulatory peritoneal dialysis (CAPD) patients is limited. METHODS: This retrospective cohort study was conducted in incident CAPD patients. The demographic characteristics, laboratory parameters, and CVD readmission were collected and analyzed. The primary outcome was all-cause mortality, and the secondary outcomes included CVD mortality, infection-related mortality and technique failure. A logistic regression was used to identify the risk factors associated with CVD readmission within the first year after dialysis. Cox proportional hazards models were used to evaluate the association between CVD readmission and the outcomes. RESULTS: In total, 1589 peritoneal dialysis (PD) patients were included in this study, of whom 120 (7.6%) patients had at least one episode of CVD readmission within the first year after dialysis initiation. Advanced age, CVD history, and a lower level of serum albumin were independently associated with CVD readmission. CVD readmission within the first year after dialysis was significantly associated with all-cause (HR 2.66, 95%CI 1.91-3.70, p < 0.001) and CVD (HR 3.42, 95%CI 2.20-5.31, p < 0.001) mortality, but not infection-related mortality or technique failure, after adjusting for confounders. CONCLUSIONS: Our findings suggest that an advanced age, a history of CVD, and a lower level of serum albumin were independently associated with CVD readmission. Moreover, CVD readmission was associated with all-cause and cardiovascular mortality in incident CAPD patients.


Assuntos
Doenças Cardiovasculares/mortalidade , Falência Renal Crônica/terapia , Readmissão do Paciente/estatística & dados numéricos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Diálise Peritoneal Ambulatorial Contínua/mortalidade , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/etiologia , Causas de Morte , China/epidemiologia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
18.
J Hum Genet ; 65(3): 241-249, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31857673

RESUMO

Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13-1.45, P = 1.42 × 10-4) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus (CFB) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas de Ciclo Celular/genética , Glomerulonefrite por IGA/genética , Doenças Inflamatórias Intestinais/genética , Adulto , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Glomerulonefrite por IGA/patologia , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
19.
J Org Chem ; 85(5): 3287-3296, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31944119

RESUMO

The metal-free-catalyzed synthesis of allyl nitriles from Csp2-Csp3 coupling between olefins and azobis was carried out. Key on this work was that the synthesis of allyl nitriles directly using olefin as a starting material was considered to be more efficient and economical than the alkyne, alkynyl carboxylic acid, or cinnamic acid used in previous works. Moreover, in this reaction, iodine served as the sole promoter, azobis served as a cyanation reagent, and N2 was the only nontoxic byproduct that could avoid the utilization of metal catalysts and virulent nitrile reagents and generation of toxic wastes. With an optimum condition in hand, more than 30 examples of desired products including aromatic and aliphatic nitriles have been synthesized in good to excellent yields. Based on control experiments and literature data, a plausible mechanism of cyanation was proposed.

20.
J Phys Chem A ; 124(1): 215-223, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31790230

RESUMO

In this work, the studies of thermodynamic mean activity coefficients of KCl in the KCl-SrCl2-H2O ternary system have been made. A cell without liquid junction battery cell, K-ISE|KCl(mA), SrCl2(mB)|Cl-ISE, was used to study the activity coefficients in this mixed system KCl-SrCl2-H2O at 288.15 K by the electromotive force method. The total ionic strengths ranges are 0.0100-1.0000 mol·kg-1 with different ionic strength fractions yb of SrCl2, that is, yb = (0, 0.2, 0.4, 0.6, and 0.8). The results show that the K-ISE and Cl-ISE have a good Nernst response. Accordingly, the electromotive forces of the mixed system were measured by using the ion selective electrode listed above, and the mean activity coefficients are also determined with Nernst equation. Using the activity coefficient data, the mixed ion interaction parameters θK,Sr and ψK,Sr,Cl of Pitzer equations at 288.15 K were fitted by Matlab with linear regression method, respectively. Furthermore, those parameters were applied to calculate the values of the mean activity coefficients of SrCl2. Finally, the osmotic coefficients, water activity, and the excess Gibbs free energy of this system were evaluated by Pitzer's equations.

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