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Lipids Health Dis ; 18(1): 68, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885219


BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.

Códon sem Sentido , Hipertrigliceridemia/complicações , Proteínas de Membrana/genética , Obesidade Mórbida/genética , Pancreatite/genética , Fumar/genética , Adulto , Predisposição Genética para Doença , Heterozigoto , Humanos , Hipertrigliceridemia/genética , Estilo de Vida , Masculino , Pancreatite/etiologia
Pancreatology ; 19(1): 136-142, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30473463


OBJECTIVE: We aimed to evaluate whether early (first 48 h) hyperchloremia and/or the change of serum chloride concentration are associated with acute kidney injury (AKI) in patients with moderately severe and severe acute pancreatitis (MSAP and SAP). METHODS: We retrospectively collected the data of patients with a primary diagnosis of MSAP or SAP from a tertiary center between January 2014 and June 2017. Consecutive chloride levels within the first 48 h after admission were retrieved for further calculation. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to assess the relationship between hyperchloremia and AKI. RESULTS: 145 patients were enrolled for analysis, of whom 33.5% (47/145) developed hyperchloremia during the observation period. The incidence of AKI was significantly higher in the hyperchloremia group (40.4% vs 7.1%; p < 0.001). On multivariate analysis, the increase in serum chloride (Δ[Cl-]) was independently associated with AKI [OR = 1.32 (1.00-1.74)], as was chloride exposure [OR = 1.01 (1.00-1.02)], and these associations were found to be stronger in patients identified as predicted SAP (PSAP). Moreover, even in patients without hyperchloremia, increase in serum chloride (Δ[Cl-]) was still associated with AKI [OR = 1.65 (1.18-2.32)]. Area under the curve of the ROC curve (AUCROC) analysis found that Δ[Cl-] is a good predictor of AKI with an optimal cutoff point at 3.5 mmol/L, showing an AUCROC of 0.81. CONCLUSION: Hyperchloremia is common in patients with AP and Δ[Cl-] and chloride exposure during the first 48 h were independent risk factors for AKI in MSAP and SAP patients.

Lesão Renal Aguda/induzido quimicamente , Cloretos/sangue , Cloretos/toxicidade , Pancreatite/complicações , Lesão Renal Aguda/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatite/sangue , Estudos Retrospectivos
Lipids Health Dis ; 17(1): 144, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921298


BACKGROUND: Variants in the lipoprotein lipase (LPL), apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), GPIHBP1 and LMF1 genes may cause severe hypertriglyceridemia (HTG), which is now the second-leading aetiology of acute pancreatitis in China. METHODS: The patient and his family were assessed for gene variants by Sanger sequencing of exons and exon-intron junctions of the LPL, GPIHBP1, APOA5, APOC2, and LMF1 genes. Post-heparin blood was collected for LPL mass and activity detection. RESULTS: The patient had suffered from long-term severe hypertriglyceridemia and recurrent abdominal pain for over 30 years, since age 26, and 3 bouts of acute pancreatitis. Two heterozygous LPL single-nucleotide polymorphisms (SNPs) were compound but dislinked: a single-nucleotide substitution (c.42G > A) resulting in the substitution of tryptophan with a stop codon (p.W14X) in one allele, and a single-nucleotide substitution (c.835C > G) resulting in a leucine-to-valine substitution (p.L279 V) in another allele. Only one SNP, p.L279 V, was detected in his son. Post-heparin LPL activity and mass were also lower in the patient. CONCLUSION: Two heterozygous LPL SNPs, W14X and L279 V, were newly found to be compound but dislinked, which may cause long-term severe hypertriglyceridemia and recurrent acute pancreatitis.

Predisposição Genética para Doença , Hipertrigliceridemia/genética , Lipase Lipoproteica/genética , Pancreatite/genética , Polimorfismo de Nucleotídeo Único , Doença Aguda , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Sequência de Bases , Heterozigoto , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/patologia , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/diagnóstico , Pancreatite/patologia , Análise de Sequência de DNA
BMC Gastroenterol ; 18(1): 89, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29914404


BACKGROUND: Unlike western world, gallstones and hypertriglyceridemia (HTG) are among the first two etiologies of acute pancreatitis (AP) in China. But yet, detailed differences in clinical features and outcomes between hypertriglyceridemia and biliary acute pancreatitis have not been well described. METHODS: This retrospective study enrolled 730 acute pancreatitis patients from July 1, 2013 to October 1, 2016 in Jinling Hospital. The causes of the study patients were defined according to specific diagnostic criteria. The clinical features and outcomes of patients with hypertriglyceridemia acute pancreatitis (HTG-AP) and biliary acute pancreatitis (BAP) were compared in terms of general information, disease severity, laboratory data, system complications, local complications, and clinical outcome. RESULTS: In the enrolled 730 AP patients, 305 (41.8%) were HTG-AP, and 425 (58.2%) were BAP. Compared to BAP, the HTG-AP patients were found to be younger, with higher body mass Index (BMI), and much higher proportion of diabetes, fatty liver and high fat diet. Besides that, HTG-AP patients had significantly higher C-reactive protein (CRP) (p<0.01) and creatinine (p = 0.031), together with more acute respiratory distress syndrome (ARDS) (p = 0.039), acute kidney injury (AKI) (p<0.001), deep venous thrombosis (p = 0.008) and multiple organ dysfunction syndrome (MODS) (p = 0.032) in systematic complications. As for local complications, HTG-AP patients had significantly less infected pancreatitis necrosis (p = 0.005). However, there was no difference in mortality, hospital duration and costs between the groups. CONCLUSION: HTG-AP patients were younger, more male, having high fat diet and with higher BMI compared to BAP patients. The prevalence of AKI/ARDS/DVT/MODS in HTG-AP patients was higher than BAP patients, while BAP patients had a greater possibility in development of infected pancreatitis necrosis (IPN). According to the multivariate analysis, only the complication of AKI was independently related with the etiology of HTG, however, BMI contributes to AKI, ARDS and DVT.

Cálculos Biliares/complicações , Hipertrigliceridemia/complicações , Pancreatite/etiologia , Doença Aguda , Adulto , Fatores Etários , Índice de Massa Corporal , Complicações do Diabetes , Dieta Hiperlipídica , Fígado Gorduroso/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
Exp Mol Pathol ; 101(1): 22-30, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27112840


Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-ß1 (TGF-ß1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin. Furthermore, we discovered that TGF-ß1 could induce the differentiation of lung resident mesenchymal stem cells (LR-MSCs) into fibroblasts, which may play an essential role in PF. LR-MSCs incubated with FGF-2 showed modest alterations in the expression of α-SMA and Vimentin. Moreover, in our study, we found that Wnt/ß-catenin signaling was activated both in vitro and in vivo as a result of bleomycin treatment. Interestingly, we also found that suppression of the Wnt/ß-catenin signaling could significantly attenuate bleomycin-induced PF accompanied with decreased expression of TGF-ß1 and FGF-2 in vitro and in vivo. These results support that controlling the aberrant expression of TGF-ß1 and FGF-2 via inhibition of Wnt/ß-catenin signaling could serve as a potential therapeutic strategy for PF.

Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Via de Sinalização Wnt , Animais , Bleomicina , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pulmão/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Regulação para Cima/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
J Agric Food Chem ; 55(17): 7140-3, 2007 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-17650004


Polyphenol oxidase (PPO) from litchi (Litchi chinensis Sonn.) pericarp was characterized using (-)-epicatechin, which was the major endogenous polyphenol in litchi pericarp as a substrate. The optimum pH for PPO activity with (-)-epicatechin was 7.5, and the enzyme was unstable below pH 4.5 and stable in the pH range of 6.0-8.0. Residual activities of PPO were 86.25, 86.31, and 80.17% after 67 days of incubation at 4 degrees C at pH 6.0, 7.5, and 8.0, respectively. From thermostability studies, the Ki value increased with temperature and the results suggested that the enzyme was unstable above 45 degrees C. Moreover, the results also provided strong evidence that the denaturalization temperature of PPO was near 70 degrees C. The inhibition studies indicated that l-cysteine and glutathione were strong inhibitors even at low concentrations while NaF inhibited moderately. In addition, the results also indicated that the inhibition mechanisms of thiol groups were different from those of halide salts.

Catequina/metabolismo , Catecol Oxidase/metabolismo , Frutas/enzimologia , Litchi/enzimologia , Catecol Oxidase/antagonistas & inibidores , Estabilidade Enzimática , Temperatura Alta , Concentração de Íons de Hidrogênio , Especificidade por Substrato