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1.
Cell ; 179(6): 1276-1288.e14, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31778654

RESUMO

Although human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice. Finally, aortic atherosclerotic lesions are reduced by 90% and 70%, respectively, in male and female LDLR-deficient mice upon GPR146 depletion. Taken together, these findings outline a regulatory role for the GPR146/ERK axis in systemic cholesterol metabolism and suggest that GPR146 inhibition could be an effective strategy to reduce plasma cholesterol levels and atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Hipercolesterolemia/metabolismo , Receptores Acoplados a Proteínas G/deficiência , Animais , Aterosclerose/sangue , Sequência de Bases , Colesterol/sangue , Dependovirus/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Jejum , Feminino , Hepatócitos/metabolismo , Humanos , Hipercolesterolemia/sangue , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de LDL/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Regulação para Cima
2.
FASEB J ; 37(1): e22722, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571509

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel Bunyavirus, has gradually become a threatening infectious disease in rural areas of Asia. Studies have identified a severe cytokine storm and impaired humoral immune response in SFTS. However, the cellular immune response to SFTS virus (SFTSV) infection remains largely unknown. Here we report that SFTS patients had a cytokine storm accompanied by high levels of chemokines. CD8+ T cells in peripheral blood mononuclear cells of SFTS patients exhibited a more activated phenotype and enhanced the antiviral responses. They increased the expression of CD69 and CD25, secreted a higher level of IFN-γ and granzyme, and had a stronger proliferative ability than in healthy controls. In convalescent SFTS patients, the expression of CD69 and CD25 on CD8+ T cells was reduced. In addition, we found the ratio and cellularity of CD14+ CD16+ intermediate monocytes were increased in peripheral blood of SFTS patients. Both the expression of C-X-C motif chemokine ligand 10 (CXCL10) on CD14+ CD16+ intermediate monocytes and the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD8+ T cells increased dramatically in SFTS patients. Our studies reveal a potential pathway that CD8+ T cells rapidly activate and are mostly recruited by intermediate monocytes through CXCL10 in SFTSV infection. Our results may be of clinical relevance for further treatment and discharge instructions in SFTSV infections.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Infecções por Bunyaviridae/tratamento farmacológico , Linfócitos T CD8-Positivos , Leucócitos Mononucleares , Síndrome da Liberação de Citocina , Trombocitopenia/tratamento farmacológico , Antivirais/uso terapêutico
3.
Microb Pathog ; 173(Pt A): 105819, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36216207

RESUMO

BACKGROUND: Neonatal pneumonia is a common illness in the neonatal period with a high fatality rate. Accumulating proofs have attested to the crucial role of circular RNAs (circRNAs) in pneumonia. This study was intended to expound on the function of circ_0038467 and the underlying mechanism in lipopolysaccharide (LPS)-stimulated 16HBE cell injury in neonatal pneumonia. METHODS: 16HBE cells were exposed to LPS to establish an in vitro neonatal pneumonia cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for detecting the levels of circ_0038467, microRNA-545-3p (miR-545-3p), and tumor necrosis factor receptor-associated factor 1 (TRAF1) in neonatal pneumonia serums and LPS-treated 16HBE cells. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and flow cytometry assays were used to examine cell viability, proliferation, and apoptosis, respectively. The protein abundances of proliferation/apoptosis/inflammation-correlated makers and TRAF1 were tested by Western blot. RNase R and Actinomycin D assays were implemented to determine the features of circ_0038467. The mutual effect between miR-545-3p and circ_0038467 or TRAF1 was affirmed by a dual-luciferase reporter and RNA pull-down assay assays. RESULTS: Circ_0038467 was upregulated in neonatal pneumonia serum specimens and LPS-triggered 16HBE cells. LPS administration restrained 16HBE cell proliferation and promoted apoptosis and inflammation, whereas circ_0038467 silence recovered these influences. Meanwhile, miR-545-3p was targeted by circ_0038467, and circ_0038467 could modulate LPS-treated 16HBE cell injury through absorbing miR-545-3p. Furthermore, circ_0038467 controlled TRAF1 level via segregating miR-545-3p. Moreover, TRAF1 overexpression relieved the suppressive impact of circ_0038467 silence in LPS-triggered 16HBE cell detriment. CONCLUSION: Circ_0038467 knockdown mitigated LPS-exposed 16HBE cell damage through regulating miR-545-3p/PPARA axis.


Assuntos
MicroRNAs , Pneumonia , RNA Circular , Fator 1 Associado a Receptor de TNF , Humanos , Recém-Nascido , Apoptose , Proliferação de Células , Inflamação , Lipopolissacarídeos , MicroRNAs/genética , Fator 1 Associado a Receptor de TNF/genética , RNA Circular/genética
4.
Cladistics ; 38(6): 649-662, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35779275

RESUMO

Marchantiopsida (complex thalloid liverworts) are one of the earliest lineages of embryophytes (land plants), and well-known for their air pores and chambers, pegged rhizoids, and absence of organellular RNA editing sites. Despite their importance to an understanding of early embryophyte evolution, many key nodes within this class remain poorly resolved, owing to the paucity of genetic loci previously available for phylogenetic analyses. Here, we sequenced 54 plastomes, representing 28 genera, nearly all families, and all orders of Marchantiopsida. Based on these plastomes, we present a hypothesis of deep relationships within the class, and make the first investigations of gene contents and synteny. Overall, the Marchantiopsida plastomes were well-conserved, with the exception of the genus Cyathodium that has plastomes with higher GC content, fewer single sequence repeats (SSRs), and more structural variations, implying that this genus might possess RNA editing sites. Abundant repetitive elements and six highly divergent regions were identified as suitable for future infrafamilial taxonomic studies. The phylogenetic topology of Sphaerocarpales, Neohodgsoniales and Blasiales within Marchantiopsida was essentially congruent with previous studies but generally we obtained higher support values. Based on molecular evidence and previous morphological studies, we include Lunulariales in Marchantiales and suggest the retention of narrowed delimitation of monotypic families. The phylogenetic relationships within Marchantiales were better resolved, and 13 monophyletic families were recovered. Our analyses confirmed that the loss of intron 2 of ycf3 is a synapomorphy of Marchantiidae. Finally, we propose a new genus, Asterellopsis (Aytoniaceae), and present an updated classification of Marchantiopsida. The highly supported phylogenetic backbone provided here establishes a framework for future comparative and evolutionary studies of the complex thalloid liverworts.


Assuntos
Embriófitas , Genoma de Cloroplastos , Hepatófitas , Humanos , Filogenia , Genoma de Cloroplastos/genética , Hepatófitas/genética , Sintenia , Embriófitas/genética
5.
J Pediatr Hematol Oncol ; 44(1): e217-e222, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34986134

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome in children, and the knowledge of it is still limited. Two hundred twenty-seven children with HLH in our hospital were retrospectively analyzed from January 2001 to December 2018. The age of the patients on admission ranged from 1 day to 14 years old. The 3 most common clinical manifestations include fever (98.7%), hepatomegaly (95.6%), and splenomegaly (92.1%). The decrease of high-density lipoprotein cholesterol (99.1%) is very common in children with HLH. Albumin<25 g/L, activated partial thromboplastin time >65 s, and lactose dehydrogenase >1000 U/L were independent risk factors for poor early prognosis in children with HLH, and their odds ratio values were 2.515, 3.094, and 2.378, respectively, while age >28 months was identified as a protective factor (odds ratio=0.295). Of the 227 children, 67 (29.52%) died within 30 days of onset. The mortality rate in 2013 to 2018 was significantly lower than that in 2001 to 2012 (16.35% vs. 40.65%, P=0.000). The shortening of the time from onset to admission and the reduction of time from admission to definite diagnosis could be some of the reasons for the decrease of HLH mortality in 2013 to 2018 (P<0.05, respectively). Our study suggests that early identification of risk factors for HLH, timely diagnosis and treatment are important measures to improve the short-term prognosis of HLH in children.


Assuntos
HDL-Colesterol/sangue , Linfo-Histiocitose Hemofagocítica , Albumina Sérica Humana/metabolismo , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Tempo de Tromboplastina Parcial , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
6.
Pak J Med Sci ; 38(8): 2318-2323, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415270

RESUMO

Objectives: To determine the correlation between the expression of silent information regulator 1 (SIRT1) and enhancer of zeste two polycomb repressive complex two subunit (EZH2) and peritoneal function in patients with diabetic nephropathy (DN) and peritoneal dialysis. Methods: One hundred forty patients with DN underwent peritoneal dialysis in Hanchuan People's Hospital from April 2016 to January 2019 were divided into four groups according to the duration of peritoneal dialysis. The levels of SIRT1 and EZH2 in serum were measured. The ratio of dialysate to plasma creatinine (D/Pcr) and the concentration of cancer antigen 125 (CA125) in peritoneal dialysate were determined. The ratio of urea clearance to urea distribution volume (Kt/V) of dialyzer was calculated. The correlations between SIRT1 and EZH2 expressions and peritoneal function were analyzed. Results: With the prolongation of peritoneal dialysis, serum SIRT1 expression, Kt/V, Ccr and CA125 decreased, while EZH2 expression and D/Pcr increased in patients with DN undergoing peritoneal dialysis. Pearson's correlation analysis showed that SIRT1 expression was negatively correlated with D/Pcr while positively correlated with Kt/V and CA125, and serum EZH2 expression was negatively correlated with Kt/V and CA125 while positively correlated with D/Pcr. ROC analysis demonstrated that SIRT1 and EZH2 expressions had certain diagnostic value for the poor prognosis of patients with DN undergoing peritoneal dialysis. Conclusion: Serum SIRT1 and EZH2 expressions in patients with DN undergoing peritoneal dialysis are closely related to their peritoneal function. They have certain diagnostic value for the poor prognosis of patients with DN undergoing peritoneal dialysis.

7.
Appl Environ Microbiol ; 87(24): e0155221, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34586903

RESUMO

Silicate mineral weathering (dissolution) plays important roles in soil formation and global biogeochemical cycling. In this study, a combination of genomics, transcriptomics, and genetics was used to identify the molecular basis of mineral weathering activity and acid tolerance in Pseudomonas azotoformans F77. Biotite was chosen as a silicate mineral to investigate mineral weathering. The genome of strain F77 was sequenced, and the genes significantly upregulated when grown in the presence of biotite included mineral weathering-related genes associated with gluconic acid metabolism, flagellar assembly, and pilus biosynthesis and acid tolerance-related genes associated with neutralizing component production, reducing power, and proton efflux. The biotite-weathering behaviors of strain F77 and its mutants that were created by deleting the tkt, tal, and gntP genes, which are involved in gluconic acid metabolism, and the potF, nuoF, and gdtO genes, which are involved in acid tolerance, were determined. The Fe and Al concentrations in the strain F77-inoculated medium increased 2.2- to 13.7-fold compared to the controls. The cell numbers of strain F77 increased over time, while the pH values in the medium ranged from 3.75 to 3.90 between 20 and 36 h of incubation. The release of Al and Fe was significantly reduced in the F77 Δtal, F77 ΔgntP, F77 ΔpotF, and F77 ΔnuoF mutants. Bacterial growth was significantly reduced in the presence of biotite in the F77 ΔpotF and F77 ΔnuoF mutants. Our results demonstrated the acid tolerance of strain F77 and suggested that multiple genes and metabolic pathways in strain F77 are involved in biotite weathering and acid tolerance during the mineral weathering process. IMPORTANCE Acid production and tolerance play important roles in effective and persistent mineral weathering in bacteria, although the molecular mechanisms governing acid production and acid tolerance in bacteria have not been fully elucidated. In this study, the molecular mechanisms underlying biotite (as a silicate mineral) weathering (dissolution) and acid tolerance of P. azotoformans F77 were characterized using genomics, transcriptomics, and genetics analyses. Our results showed that the genes and metabolic pathways for gluconic acid metabolism, flagellar assembly, and pilus biosynthesis may play important roles in mineral weathering by strain F77. Notably, the genes associated with neutralizing component production, reducing power, and proton efflux may be related to acid tolerance in strain F77. The expression of these acid production- and acid tolerance-related genes was observed to be increased by biotite in strain F77. Our findings may help to elucidate the molecular mechanisms governing mineral weathering and, especially, acid tolerance in mineral-weathering bacteria.


Assuntos
Minerais/metabolismo , Pseudomonas , Silicatos/metabolismo , Genômica , Fenótipo , Prótons , Pseudomonas/genética , Pseudomonas/metabolismo , Transcriptoma
8.
Appl Environ Microbiol ; 86(7)2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-31953343

RESUMO

In this study, the mineral-weathering bacterium Pseudomonas azotoformans F77, which was isolated from the soil of a debris flow area, was evaluated for its weathering activity under direct contact with biotite or without contact. Then, biotite-weathering behaviors of strain F77, mutants that had been created by deleting the gcd and adh genes (which are involved in gluconic acid metabolism and pilus formation, respectively), and the double mutant F77ΔgcdΔadh were compared. The relative gene expression levels of F77 and its mutants F77Δgcd and F77Δadh were also analyzed in the presence of biotite. Direct contact with biotite increased Fe and Al release from the mineral in the presence of F77. All strains had similar abilities to release Fe and Al from the mineral except for F77Δgcd and F77Δadh Mobilized Fe and Al concentrations were decreased by up to 72, 26, and 87% in the presence of F77Δgcd, F77Δadh, and F77ΔgcdΔadh, respectively, compared to levels observed in the presence of F77 during the mineral-weathering process. Gluconic acid production was decreased for F77Δgcd and F77ΔgcdΔadh, while decreased cell attachment on the mineral surface was observed for F77Δadh, compared to findings for F77. The F77 genes involved in pilus formation and gluconic acid metabolism showed increased expression levels in the presence of biotite. The results of this study showed important roles for the genes involved in gluconic acid metabolism and pilus formation in mineral weathering by F77 and demonstrated the distinctive effect of these genes on mineral weathering by F77.IMPORTANCE Bacteria play important roles in mineral weathering and soil formation, although the molecular mechanisms underlying the interactions between bacteria and silicate minerals are poorly understood. In this study, the interactions between biotite and the highly effective mineral-weathering bacterium P. azotoformans F77 were characterized. Our results showed that the genes involved in gluconic acid metabolism and pilus formation play important roles in mineral weathering by F77. The presence of biotite could promote the expression of these genes in F77, and a distinctive effect of these genes on mineral weathering by F77 was observed in this study. Our results provide new knowledge and promote better understanding regarding the interaction between silicate minerals and mineral-weathering bacteria, as well as the molecular mechanisms involved in these processes.


Assuntos
Silicatos de Alumínio/metabolismo , Compostos Ferrosos/metabolismo , Minerais/metabolismo , Pseudomonas/metabolismo , Microbiologia do Solo
9.
Glob Chang Biol ; 26(9): 5267-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32614503

RESUMO

We assessed the response of soil microbial nitrogen (N) cycling and associated functional genes to elevated temperature at the global scale. A meta-analysis of 1,270 observations from 134 publications indicated that elevated temperature decreased soil microbial biomass N and increased N mineralization rates, both in the presence and absence of plants. These findings infer that elevated temperature drives microbially mediated N cycling processes from dominance by anabolic to catabolic reaction processes. Elevated temperature increased soil nitrification and denitrification rates, leading to an increase in N2 O emissions of up to 227%, whether plants were present or not. Rates of N mineralization, denitrification and N2 O emission demonstrated significant positive relationships with rates of CO2 emissions under elevated temperatures, suggesting that microbial N cycling processes were associated with enhanced microbial carbon (C) metabolism due to soil warming. The response in the abundance of relevant genes to elevated temperature was not always consistent with changes in N cycling processes. While elevated temperature increased the abundances of the nirS gene with plants and nosZ genes without plants, there was no effect on the abundances of the ammonia-oxidizing archaea amoA gene, ammonia-oxidizing bacteria amoA and nirK genes. This study provides the first global-scale assessment demonstrating that elevated temperature shifts N cycling from microbial immobilization to enhanced mineralization, nitrification and denitrification in terrestrial ecosystems. These findings infer that elevated temperatures have a profound impact on global N cycling processes with implications of a positive feedback to global climate and emphasize the close linkage between soil microbial C and N cycling.


Assuntos
Nitrificação , Solo , Archaea/genética , Desnitrificação , Ecossistema , Nitrogênio , Microbiologia do Solo , Temperatura
10.
Respir Res ; 21(1): 171, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631317

RESUMO

BACKGROUND: There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change of LDH in COVID-19 pneumonia has not been well investigated. METHODS: Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (- 1 ~ + 1 day). RESULTS: At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression. CONCLUSIONS: Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.


Assuntos
Infecções por Coronavirus/sangue , Progressão da Doença , L-Lactato Desidrogenase/sangue , Pneumonia Viral/sangue , Radiografia Torácica/métodos , Adulto , Idoso , Biomarcadores/sangue , COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
11.
Genes Immun ; 20(6): 500-508, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30245508

RESUMO

Genome-wide association studies (GWASs) have discovered >50 risk loci for type 1 diabetes (T1D). However, those variations only have modest effects on the genetic risk of T1D. In recent years, accumulated studies have suggested that gene-gene interactions might explain part of the missing heritability. The purpose of our research was to identify potential and novel risk genes for T1D by systematically considering the gene-gene interactions through network analyses. We carried out a novel system network analysis of summary GWAS statistics jointly with transcriptomic gene expression data to identify some of the missing heritability for T1D using weighted gene co-expression network analysis (WGCNA). Using WGCNA, seven modules for 1852 nominally significant (P ≤ 0.05) GWAS genes were identified by analyzing microarray data for gene expression profile. One module (tagged as green module) showed significant association (P ≤ 0.05) between the module eigengenes and the trait. This module also displayed a high correlation (r = 0.45, P ≤ 0.05) between module membership (MM) and gene significant (GS), which indicated that the green module of co-expressed genes is of significant biological importance for T1D status. By further describing the module content and topology, the green module revealed a significant enrichment in the "regulation of immune response" (GO:0050776), which is a crucially important pathway in T1D development. Our findings demonstrated a module and several core genes that act as essential components in the etiology of T1D possibly via the regulation of immune response, which may enhance our fundamental knowledge of the underlying molecular mechanisms for T1D.


Assuntos
Diabetes Mellitus Tipo 1/genética , Redes Reguladoras de Genes , Transcriptoma , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/imunologia , Estudo de Associação Genômica Ampla , Genômica , Humanos
12.
Development ; 143(9): 1475-81, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27143754

RESUMO

Hepatocyte-like cells (HLCs) are derived from human pluripotent stem cells (hPSCs) in vitro, but differentiation protocols commonly give rise to a heterogeneous mixture of cells. This variability confounds the evaluation of in vitro functional assays performed using HLCs. Increased differentiation efficiency and more accurate approximation of the in vivo hepatocyte gene expression profile would improve the utility of hPSCs. Towards this goal, we demonstrate the purification of a subpopulation of functional HLCs using the hepatocyte surface marker asialoglycoprotein receptor 1 (ASGR1). We analyzed the expression profile of ASGR1-positive cells by microarray, and tested their ability to perform mature hepatocyte functions (albumin and urea secretion, cytochrome activity). By these measures, ASGR1-positive HLCs are enriched for the gene expression profile and functional characteristics of primary hepatocytes compared with unsorted HLCs. We have demonstrated that ASGR1-positive sorting isolates a functional subpopulation of HLCs from among the heterogeneous cellular population produced by directed differentiation.


Assuntos
Receptor de Asialoglicoproteína/metabolismo , Células-Tronco Embrionárias/citologia , Citometria de Fluxo/métodos , Hepatócitos/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Albuminas/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular , Membrana Celular/metabolismo , Citocromos/metabolismo , Humanos , Ureia/metabolismo
13.
BMC Cancer ; 19(1): 795, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409405

RESUMO

BACKGROUND: The real-world incidence of chronic liver damage after transarterial chemoembolization (TACE) is unclear. LiverT, a retrospective, observational study, assessed liver function deterioration after a single TACE in real-world hepatocellular carcinoma (HCC) patients in US practice. METHODS: Eligible HCC patients identified from Optum's integrated database using standard codes as having had an index TACE between 2010 and 2016 with no additional oncologic therapy in the subsequent 3 months. At least one laboratory value (bilirubin, albumin, aspartate transaminase [AST], alanine transaminase [ALT], international normalized ratio [INR]) was required at baseline and the acute (≤29 days after TACE) and chronic (30-90 days after TACE) periods. Due to lack of universally accepted liver function deterioration criteria, clinically meaningful changes in laboratory parameters were pre-defined by authors (FP, RM, and SO). RESULTS: Of the 3963 TACE patients, 572 were eligible for analyses. Deterioration of liver function from baseline occurred in the acute period and persisted in the chronic period (bilirubin 30 and 23%, albumin 52 and 31%, AST 44 and 25%, ALT 43 and 25%, INR 25 and 15%, respectively). In a subgroup analysis, a higher proportion of patients with diabetes had deterioration in AST and ALT. CONCLUSIONS: A clinically meaningful proportion of real-world HCC patients had deterioration of liver function-related laboratory values 30-90 days after a single TACE in modern US practice. Future electronic health record research may help determine causality. The present findings highlight the need for the careful selection of patients for TACE, which is important to help optimize the benefit of the overall HCC treatment course.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Anal Biochem ; 577: 34-41, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991019

RESUMO

Human telomerase reverse transcriptase (hTERT) mRNA in tissue is a biomarker of lung cancer, but hTERT mRNA in sputum had not been successfully detected with conventional reverse transcription PCR methods. Here, we developed a novel PCR protocol: Template-Ready PCR (TRPCR), to detect sputum hTERT mRNA, in which probes serve as templates of amplification. While free probes and dsDNA were removed in template preparation through aspiration and restriction digestion, probes that formed into heterocomplex with target RNA remained intact for PCR amplification. By fishing out the heterocomplex and amplifying the probes, TRPCR achieved sensitivity higher than reverse transcription-quantitative PCR (RT-qPCR). ROC curve of sputum hTERT mRNA by TRPCR assay showed the discrimination in high sensitivity and specificity between patients with lung cancer and lung cancer-free donors at the PCR Ct cutoff of 33. We further validated this approach through TRPCR assay of sputum from 858 lung cancer patients and 480 non-malignant pulmonary disease patients. 722 (84.2%) cases from 858 with lung cancer patients were detected as positive, whereas 461 (96.0%) cases from 480 non-malignant pulmonary disease patients were detected as negative, suggesting that TRPCR assay of sputum hTERT mRNA can serve as a non-invasive molecular diagnosis of lung cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , Escarro/química , Telomerase/metabolismo , Células A549 , Humanos
15.
BMC Health Serv Res ; 19(1): 610, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470846

RESUMO

BACKGROUND: Even though China launched a series of measures to alleviate several financial burdens (including health insurance scheme, increased government investment, and so on), the economic burden of health expenditure has still not been alleviated. Out-of-pocket payments (OPPs) show not only a time correlation but also some degree of spatial correlation. The aims of the current study were thus to identify the spatial cluster of OPPs, to investigate the main factors affecting variation, and to explore the spatial spillover sources of China's OPP. METHODS: Global and local spatial autocorrelation tests were validated to identify the spatial cluster of OPPs using the panel data of 31 provinces in China from 2005 to 2016. The Spatial Durbin Model, established in this paper, measured the spatial spillover effect of OPPs and analyzed the possible spillover sources (demand, supply, and socio-economic factors. RESULTS: OPPs were found to have a significant and positive spatial correlation. The results of the Spatial Durbin Model showed the direct and indirect effects of demand, supply, and socio- economic factors on China's OPPs. Among the demand factors, the direct and indirect correlation (elasticity) coefficients were positive. Among the supply factors, the direct and indirect effects of the share of primary health beds on residents' OPPs were negative. The ratio of health technicians in hospitals to those in primary health institutions on per capital OPPs had a significant indirect effect. Among the socio-economic factors, the direct effects of GDP, government health expenditure, and urbanization on OPPs were found to be positive. There were no significant indirect effects of socio-economic factors on OPPs. CONCLUSION: This paper finds that China's OPPs are not randomly distributed but, overall, present a positive spatial cluster, even though a series of measures have been launched to promote health equity. Socio-economic factors and those associated with demand were found to be the main influences of variation in OPPs, while demand was seen to be the driver of the positive spatial spillover of OPPs, whereby effective supply could inhibit these positive spillover effects.


Assuntos
Gastos em Saúde/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , China , Equidade em Saúde/economia , Equidade em Saúde/estatística & dados numéricos , Humanos , Seguro Saúde/economia , Investimentos em Saúde , Análise Espaço-Temporal , Urbanização
16.
HPB (Oxford) ; 21(1): 107-113, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30017783

RESUMO

BACKGROUND: To investigate the clinical value of the alpha-fetoprotein (AFP) response following transcatheter arterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (HCC). METHODS: Data on patients with Barcelona Clinic Liver Cancer B staging system were analyzed. An AFP response was defined as a decrease in AFP of more than 20% after a TACE session. The association between AFP response and treatment outcome regarding imaging response and overall survival (OS) was explored. Cox proportional hazards models were applied to identify independent risk factors for OS after TACE. RESULTS: Of the enrolled 376 patients with elevated serum AFP >20 ng/mL, 214 (57%) with AFP responses were identified. AFP responders had improved median survival than non-responders (20 vs. 12 months, P = 0.002). AFP response was significantly correlated with imaging response (P < 0.001). The Cox proportional hazards model revealed that AFP response was an independent factor for OS (hazard ratio, 0.59; 95% confidence interval, 0.45-0.78; P < 0.001). In stratified analyses, an AFP response achieved improved survival in patients with tumor diameters ≤5 cm, diameters >5 cm, tumor number ≤3 and without underlying cirrhosis. CONCLUSIONS: The AFP response indicates enhanced survival after TACE in patients with intermediate-stage BCLC.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Neoplasias Primárias Múltiplas/terapia , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/sangue , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
18.
Ecotoxicol Environ Saf ; 148: 269-274, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29069614

RESUMO

A Cd-resistant and immobilizing Bacillus megaterium H3 was characterized for its impact on the biomass and quality and heavy metal uptake of edible tissues of two vegetables (Brassica campestris L. var. Aijiaohuang and Brassica rapa L. var. Shanghaiqing) grown in heavy metal-polluted soil. The impact of strain H3 on the soil quality was also evaluated. The increase in the edible tissue biomass and the contents of soluble proteins and vitamin C of the vegetables inoculated with strain H3 ranged from 18% to 33%, 17% to 31%, and 15% to 19%, respectively, compared with the controls. Strain H3 significantly decreased the edible tissue Cd and Pb contents of the two greens (41-80%), DTPA-extractable Cd content (35-47%) of the rhizosphere soils, and Cd and Pb translocation factors (25-56%) of the greens compared with the controls. Moreover, strain H3 significantly increased the organic matter content (17-21%) and invertase activity (13-14%) of the rhizosphere soils compared with the controls. Our results demonstrated the increased edible tissue biomass and quality, decreased Cd and Pb uptake of the edible tissues, and improved soil quality in the presence of strain H3. The results also suggested an effective bacterial-enhanced technique for decreased metal uptake of greens and improved vegetable and soil qualities in the metal-contaminated soils.


Assuntos
Bacillus megaterium/crescimento & desenvolvimento , Brassica/crescimento & desenvolvimento , Cádmio/análise , Poluentes do Solo/análise , Solo/normas , Verduras/crescimento & desenvolvimento , Bacillus megaterium/efeitos dos fármacos , Biomassa , Brassica/metabolismo , Cádmio/metabolismo , Chumbo/metabolismo , Chumbo/toxicidade , Rizosfera , Solo/química , Microbiologia do Solo/normas , Poluentes do Solo/metabolismo , Verduras/metabolismo
19.
World J Microbiol Biotechnol ; 35(1): 2, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30536084

RESUMO

Microorganisms play important role in mineral weathering. However, little is known about rock-associated mineral-dissolving bacteria. In this study, 129 bacterial isolates were obtained from the less and more weathered mica schist surfaces and the adjacent soil and characterized for mineral dissolving activity, population, and the linkage of rock weathering level and distribution of the bacteria. Among the 129 isolates, 112 isolates could dissolve biotite. The relative abundance of the highly effective Fe solubilizers was significantly higher on the more altered rock surface (89.6%) than in the soil (51.2%) and on the less altered rock surface (22.5%), while the relative abundance of the highly effective Si solubilizers was significantly higher in the soil (65.9%) than on the more (41.7%) and less (12.5%) altered rock surfaces. Furthermore, 17.5-42.5%, 87.5%, and 60.9-90.2% of the highly effective acid- and siderophore-producing isolates were obtained in the less and more weathered rocks and the soil, respectively. The mineral-dissolving bacteria belonged to 18 genera and Burkholderia, Bacillus, and Paenibacillus were the dominant and highly effective mineral-dissolving bacteria. Phylogenetic analysis found 2, 9, and 5 bacterial species in the highly effective mineral-dissolving bacteria on the less and more altered rock surfaces and in the soil, respectively. The results showed the abundant and diverse mineral-dissolving bacterial populations on the more weathered rock surfaces. The results also suggested distinct mineral-dissolving activities and mechanisms of the bacteria and highlighted the possibility for the development of bacterial inocula for plant nutrition improvement in silicate mineral-rich soils.


Assuntos
Silicatos de Alumínio , Bactérias/classificação , Bactérias/isolamento & purificação , Biota , Minerais/metabolismo , Microbiologia do Solo , Bactérias/metabolismo , Filogenia
20.
Ecotoxicol Environ Saf ; 138: 56-63, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28011421

RESUMO

Two metal-resistant Bacillus megaterium H3 and Neorhizobium huautlense T1-17 were investigated for their immobilization of Cd in solution and tissue Cd accumulation of rice (Oryza sativa wuyun-23) in the Cd-contaminated soil. Strains H3 and T1-17 decreased 79-96% of water-soluble Cd in solution and increased grain biomass in the high Cd-contaminated soil. Inoculation with H3 and T1-17 significantly decreased the root (ranging from 25% to 58%), above-ground tissue (ranging from 13% to 34%), and polished rice (ranging from 45% to 72%) Cd contents as well as Cd bioconcentration factor of the rice compared to the controls. Furthermore, H3 and T1-17 significantly reduced the exchangeable Cd content of the rhizosphere soils compared with the controls. Notably, strain T1-17 had significantly higher ability to reduce Cd bioconcentration factor and polished rice Cd uptake than strain H3. The results demonstrated that H3 and T1-17 decreased the tissue (especially polished rice) Cd uptake by decreasing Cd availability in soil and Cd bioconcentration factor and the effect on the reduced polished rice Cd uptake was dependent on the strains. The results may provide an effective synergistic bioremediation of Cd-contaminated soils in the bacteria and rice plants and bacterial-assisted safe production of rice in Cd-contaminated soils.


Assuntos
Bacillus megaterium/metabolismo , Cádmio/metabolismo , Metais Pesados/metabolismo , Oryza/metabolismo , Rhizobium/metabolismo , Poluentes do Solo/metabolismo , Biodegradação Ambiental , Biomassa , Cádmio/análise , Grão Comestível/química , Metais Pesados/análise , Raízes de Plantas/metabolismo , Rizosfera , Solo/química , Poluentes do Solo/análise
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