RESUMO
HyperCKemia is a rare condition characterized by a persistent increase in serum creatine kinase (CK) levels or some isoenzymes. Usually, there are no clinical, electromyography or histological manifestations, which involves a challenge at the time of diagnosis. The patient in question showed no characteristic signs or symptoms, apart from fatigue and post-exercise myalgia. Assessment was performed by rheumatology and endocrinology, determination of total CK and MB fraction in blood, and electromyography and protein electrophoresis were requested as part of the approach. This case report is considered as novel, interesting, and useful for clinical practice as few similar ones were found in the scientific literature. The difficult etiological diagnosis of this entity, and the algorithm used to arrive at it, are all presented. It is concluded that in those patients with hyperCKemia of unknown etiology, this diagnosis should be kept in mind, and be confirmed by performing a CK electrophoresis.
La hiperCKemia es una condición poco frecuente caracterizada por un aumento persistente de los niveles de creatina quinasa (CK) sérica o de algunas isoenzimas, sin que suelan presentarse manifestaciones clínicas, electromiográficas o histológicas, lo cual implica un desafío a la hora del diagnóstico. El paciente cuyo caso se presenta aquí no mostró signos o síntomas característicos, únicamente fatiga y mialgias posteriores al ejercicio. Se llevó a cabo valoración por reumatología y endocrinología, determinación de CK total y fracción MB en sangre; además, se solicitó electromiografía y electroforesis de proteínas como parte del abordaje. Consideramos que este reporte de caso es novedoso, interesante y de utilidad para la práctica clínica pues se encuentran pocos similares en la literatura científica; adicionalmente, se pone en evidencia el difícil diagnóstico etiológico de esta entidad, así como el algoritmo utilizado para llegar a ella. Se concluye que este diagnóstico debe tenerse en mente en aquellos pacientes con hiperCKemia de etiología desconocida, y para confirmarlo es necesario hacer una electroforesis de CK.
Assuntos
Humanos , Masculino , Adulto , Transferases , Creatina Quinase , Enzimas e Coenzimas , EnzimasRESUMO
INTRODUCCIÓN: Las alteraciones del perfil hepático durante el embarazo ocurren en 3-5% de las gestantes. Una nueva etiología que se ha presentado en el contexto de pandemia actual es el síndrome respiratorio agudo severo relacionado con el nuevo coronavirus (SARS-CoV-2). Éste es responsable de alteraciones hepáticas en 2 a 11% de la población general infectada por este virus, y de hasta un 30% en las embarazadas que se infectan con SARS-CoV-2. Con el objetivo de mostrar una presentación poco frecuente del SARS-CoV-2 se expone un caso clínico de elevación de transaminasas en embarazada inducida por este nuevo virus. CASO CLÍNICO: Paciente de 36 años, cursando embarazo de 20+6 semanas, consulta por dolor abdominal asociado a ictericia y coluria. Se solicita estudio donde destaca elevación de transaminasas. Ecografía abdominal con vía biliar fina. Se descartan diferentes etiologías de hepatitis aguda y crónica (dada la falta de antecedentes). Finalmente se solicita PCR para COVID-19 que resulta positiva. CONCLUSIÓN: Luego de un estudio exhaustivo de diferentes etiologías de elevación de transaminasas, se atribuye esta alteración enzimática a SARS-CoV-2. Se decide seguimiento ambulatorio estricto con pruebas hepáticas cada dos semanas. La paciente evoluciona estable con exámenes normales luego de un mes desde que se indica el alta hospitalaria. Después de descartar etiologías frecuentes de elevación de transaminasas durante el embarazo, sugerimos solicitar el estudio de este virus con PCR para COVID-19, ya que podría ser una presentación poco frecuente de SARS-CoV-2.
INTRODUCTION: Approximately 3-5% of women present alterations of hepatic enzymes during pregnancy. Under the new circumstances that the world is facing with the SARS-COV2 pandemic, a new etiology for hepatic enzyme alterations has risen. The severe acute respiratory syndrome that the novel coronavirus causes is responsible for hepatic enzyme alterations in 2 to 11% of the sick population that did not have a previous underlying hepatic condition. Furthermore, hepatic enzyme alterations in pregnant women infected with SARS-COV2 presents in up to 30% of the cases. An infrequent presentation of SARS-COV2 is presented as our clinical case. CLINICAL CASE: A 36-year-old patient with a 20+6 week pregnancy presents abdominal pain, jaundice and choluria. General blood workup shows elevated transaminases. The abdominal ultrasound revealed a thin bile duct. Acute and chronic hepatitis etiologies were discarded. Finally, a PCR of COVID-19 was solicited, which turned out to be positive. CONCLUSIÓN: After an exhaustive study to determine the etiology of the elevated transaminases, the hepatic alterations were attributed to SARS-COV2 infection. A conservative management was adopted, with outpatient follow-up with liver testing every two weeks. The patient progresses with a stable steady decline in hepatic enzyme levels, and one-month post hospital discharge, her transaminases had reached normal values. Based on this clinical case, after ruling out frequent etiologies for elevated transaminases during pregnancy, it seems reasonable to request a PCR for COVID-19, since it could be a rare presentation of SARS-CoV-2.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/enzimologia , Complicações Infecciosas na Gravidez/etiologia , Infecções por Coronavirus/complicações , Betacoronavirus , Pneumonia Viral/enzimologia , Transferases/análise , Infecções por Coronavirus/enzimologia , Fosfatase Alcalina/análise , Pandemias , Icterícia , Hepatopatias/enzimologia , Hepatopatias/etiologiaRESUMO
PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.
Assuntos
Humanos , Alanina , Antibacterianos , Bilirrubina , Diagnóstico , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Registros Eletrônicos de Saúde , Testes Hematológicos , Hepatite , Hospitalização , Hospitais Universitários , Incidência , Pacientes Internados , Fígado , Hepatopatias , Programas de Rastreamento , Prontuários Médicos , Metotrexato , Farmacoepidemiologia , Estudos Retrospectivos , TransferasesRESUMO
BACKGROUND: Common buckwheat (Fagopyrum esculentum) is an important staple food crop in southwest China, where drought stress is one of the largest limiting factors that lead to decreased crop production. To reveal the molecular mechanism of common buckwheat in response to drought stress, we performed a comprehensive transcriptomics study to evaluate gene expression profiles of common buckwheat during PEG-mediated drought treatment. RESULTS: In total, 45 million clean reads were assembled into 53,404 unigenes with an average length of 749 bp and N50 length of 1296 bp. A total of 1329 differentially expressed genes (DEGs) were identified by comparing wellwatered and drought-treated plants, out of which 666 were upregulated and 663 were downregulated. Furthermore, we defined the functional characteristics of DEGs using GO and KEGG classifications. GO enrichment analysis showed that the DEGs were significantly overrepresented in four categories, namely, "oxidoreductase activity," "oxidationreduction process," "xyloglucan:xyloglucosyl transferase activity," and "apoplast." Using KEGG pathway analysis, a large number of annotated genes were overrepresented in terms such as "plant hormone signal transduction," "phenylpropanoid biosynthesis," "photosynthesis," and "carbon metabolism." Conclusions: These results can be further exploited to investigate the molecular mechanism of common buckwheat in response to drought treatment and could supply with valuable molecular sources for abiotic-tolerant elite breeding programs in the future.
Assuntos
Estresse Fisiológico/genética , Fagopyrum/genética , Fatores de Transcrição , Transferases , Transdução de Sinais , Expressão Gênica , Análise de Sequência de RNA , Secas , Proteínas de Ligação à Clorofila , Reação em Cadeia da Polimerase em Tempo Real , TranscriptomaRESUMO
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. SCOT deficiency is caused by mutations in the OXCT1 gene, which is mapped to 5p13 and consists of 17 exons. A 12-month-old girl presented with severe ketoacidosis and was treated with continuous renal replacement therapy. She had two previously unrecognized mild-form episodes of ketoacidosis followed by febrile illness. While high levels of ketone bodies were found in her blood and urine, other laboratory investigations, including serum glucose, were unremarkable. We identified novel compound heterozygous mutations in OXCT1:c.1118T>G (p.Ile373Ser) and a large deletion ranging from exon 8 to 16 through targeted exome sequencing and microarray analysis. This is the first Korean case of SCOT deficiency caused by novel mutations in OXCT1, resulting in life-threatening ketoacidosis. In patients with unexplained episodic ketosis, or high anion gap metabolic acidosis in infancy, an inherited disorder in ketone body metabolism should be suspected.
Assuntos
Feminino , Humanos , Lactente , Equilíbrio Ácido-Base , Acidose , Glicemia , Exoma , Éxons , Corpos Cetônicos , Cetose , Metabolismo , Análise em Microsséries , Terapia de Substituição Renal , TransferasesRESUMO
1-deoxy-D-xylulose-5-phosphate synthase2(DXS2) is the first key enzyme of the MEP pathway,which plays an important role in terpene biosynthesis of plants. According to the data of Swertia mussotii transcriptome, DXS2 gene(Gen Bank number MH535905) was cloned and named as Sm DXS2. The bioinformatics results showed that Sm DXS2 has no intron,with a 2 145 bp open reading frame encoding a polypeptide of 714 amino acids. They are belonging to 20 kinds of amino acids,and the most abundant amino acids include Ala,Gly and Trp. The predicted protein molecular weight was 76. 91 k Da and its theoretical isoelectric point(p I) was6. 5,which belonging to a hydrophilic protein. α-Helix and loop were the major motifs of predicted secondary structure of DXS2. The three function domains are TPP_superfamily,Transket_pyr_ superfamily and Transketolase_C superfamily,respectively. The Sm DXS2 protein shared high identity with other DXS2 proteins of plants. Phylogenetic analysis showed that Sm DXS2 protein is grouped with the gentian DXS2 protein. The recombinant protein of Sm DXS2 gene in Escherichia coli was approximately 92. 00 k Da(containing sumo-His tag protein 13 k Da),which was consistent with the anticipated size.This work will provide a foundation for further functional research of Sm DXS2 protein and increasing the product of iridoid compound by genetic engineering in S. mussotii.
Assuntos
Sequência de Aminoácidos , Clonagem Molecular , DNA Complementar , Genética , Genes de Plantas , Iridoides , Filogenia , Proteínas de Plantas , Genética , Swertia , Genética , Transcriptoma , Transferases , GenéticaRESUMO
To investigate the effects of genistein (Gen) on the biosynthesis of N-glycolylneuraminic acid (Neu5Gc) in rats, 80 4-week-old male SD rats were randomly equally into the control and genistein groups. The rats of control and genistein groups were fed 5% ethanol and 300 mg/(kg·d) genistein respectively by gavage. The contents of Neu5Gc in hind leg muscle, kidney and liver tissues of rats were measured by using high performance liquid chromatography coupled with fluorescence detector (HPLC/FLD), and the mechanism of inhibition of Neu5Gc synthesis was investigated by using the molecular docking of Gen and sialyltransferase. On the 15th day, the content of Neu5Gc in hind leg muscle and liver tissues decreased 13.77% and 15.45%, respectively, and there was no significant change in the content of Neu5Gc in kidney tissues. On the 30th day, the content of Neu5Gc in liver tissues decreased 13.35%, however, there was no significant change in the content of Neu5Gc in kidney tissues and Neu5Gc was not detected in hind leg muscle. The content of Neu5Gc in hind leg muscle, kidney and liver tissues decreased respectively 32.65%, 32.78%, 16.80% and 12.72%, 11.42%, 12.30% while rats fed on the 45th and the 60th days. Genistein has formed the hydrogen bond with sialyltransferase activity site residues His319, Ser151, Gly293, Thr328 and formed a hydrophobic interactions with the residues His302, His301, Trp300, Ser271, Phe292, Thr328, Ser325 and Ile274. The results of molecular docking indicated that the weak intermolecular interaction was the main cause of genistein inhibiting sialyltransferase activity. The research results provided an experimental basis for the subsequent reduction of Neu5Gc in red meat before slaughter.
Assuntos
Animais , Masculino , Ratos , Regulação Enzimológica da Expressão Gênica , Genisteína , Farmacologia , Simulação de Acoplamento Molecular , Ácidos Neuramínicos , Metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Transferases , MetabolismoRESUMO
BACKGROUND: Transient elastography (FibroScan®) is a non-invasive and rapid method for assessing liver fibrosis. While the feasibility and usefulness of FibroScan® have been proven in adults, few studies have focused on pediatric populations. We aimed to determine the feasibility and usefulness of FibroScan® in Korean children. METHODS: FibroScan® examinations were performed in 106 children (age, 5–15 years) who visited the Konyang University Hospital between June and September 2018. Liver steatosis was measured in terms of the controlled attenuation parameter (CAP), while hepatic fibrosis was evaluated in terms of the liver stiffness measurement (LSM). Children were stratified into obese and non-obese controls, according to body mass index (≥ or 95% percentile) (P 5.5 kPa), whereas the remaining 29 did not (LSM < 5.5 kPa). Obese children with fibrosis had higher levels of AST (73.57 ± 56.00 vs. 39.86 ± 31.93 IU/L; P = 0.009), ALT (132.47 ± 113.88 vs. 48.66 ± 51.29 IU/L; P = 0.001), and gamma-glutamyl transferase (106.67 ± 69.31 vs. 28.80 ± 24.26 IU/L; P = 0.042) compared to obese children without fibrosis. LSM had high and significant correlation (P < 0.05) with AST, ALT, homeostasis model assessment for insulin resistance, and AST-to-platelet ratio index. CONCLUSION: FibroScan® is clinically feasible and facilitates non-invasive, rapid, reproducible, and reliable detection of hepatic steatosis and liver fibrosis in the Korean pediatric population.
Assuntos
Adulto , Criança , Humanos , Alanina Transaminase , Aspartato Aminotransferases , Índice de Massa Corporal , Diagnóstico , Técnicas de Imagem por Elasticidade , Fígado Gorduroso , Fibrose , Homeostase , Hipertensão , Resistência à Insulina , Cirrose Hepática , Fígado , Métodos , Hepatopatia Gordurosa não Alcoólica , Obesidade Abdominal , TransferasesRESUMO
PURPOSE: To estimate the roles of triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio and uric acid in predisposition for metabolic syndrome (MetS) and its components in healthy children. METHODS: Anthropometric and biochemical analyses were performed on 110 children, aged 5 to 12 years, from the Greek county of Laconia. The children were studied as a whole population and in separate groups according to age and predisposition to MetS after taking into consideration International Diabetes Federation criteria, body mass index, and lipid profile. RESULTS: Seventeen percent of children exhibited predisposition to MetS, while 39.1% had TG/HDL ratio >1, and 3.64% had high level of uric acid. According to a receiver operating characteristic curve analysis, the relative probability for MetS predisposition sextupled when TG/HDL ratio was ≥1 (odds ratio [OR], 5.986; 95% confidence interval [CI], 1.968–18.205). Children in the total population and those aged < 9 years had a greater probability for increased low-density lipoprotein (LDL) cholesterol (OR, 3.614; 95% CI, 1.561–8.365) when TG/HDL ratio was ≥ 1. The TG/HDL ratio was positively correlated with body mass index (BMI) (P=0.035) in children without MetS, cholesterol in the total population (P=0.06) and children ≥9 years old (P=0.026), and with LDL in the total population and both age groups (P=0.001). The TG/HDL ratio was also positively correlated with alanine aminotransferase in the total population (P=0.033) and gamma-glutamyl transferase in most studied groups (P<0.001). Uric acid was positively correlated with waist circumference in the total population (P=0.043) and in those without MetS (P=0.027). It was also positively correlated with BMI, TG, cholesterol, and TG/HDL ratio and negatively correlated with HDL in most studied groups (P<0.005). CONCLUSION: The studied parameters correlated with MetS components and could be characterized as effective indexes for childhood MetS, regardless of age and predisposition to MetS.
Assuntos
Criança , Humanos , Alanina Transaminase , Índice de Massa Corporal , Causalidade , Colesterol , Lipoproteínas , Curva ROC , Transferases , Ácido Úrico , Circunferência da CinturaRESUMO
Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.
Assuntos
Adulto , Feminino , Humanos , Alanina Transaminase , Fosfatase Alcalina , Aripiprazol , Aspartato Aminotransferases , Bilirrubina , Transtorno Bipolar , Dopamina , Hepatite , Hospitalização , Fígado , Testes de Função Hepática , Náusea , Palmitato de Paliperidona , Prevalência , Transtornos Psicóticos , Receptor 5-HT1A de Serotonina , Esquizofrenia , Transaminases , Transferases , VômitoRESUMO
BACKGROUND: Liver fibrosis evaluation is an important issue in chronic liver disease patients. We aimed to develop noninvasive liver fibrosis biomarkers based on transient elastography (TE, FibroScan®) through retrospective review of clinicopathological data. METHODS: We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. A total of 115 HBeAg-positive and 159 HBeAg-negative chronic hepatitis B patients were analyzed. A total of 100 hepatitis C patients were analyzed. Successful fibroscan data, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, AST, ALT, international normalized ratio of prothrombin time, total cholesterol, triglycerides, bilirubin, mean platelet volume, AST to platelet ratio index, fibrosis index based on four factors (FIB-4), neutrophil to lymphocyte ratio (NLR), and NLR to platelet ratio were analyzed to determine the new noninvasive markers for assessing liver fibrosis. RESULTS: Elevated GPR (OR=9.1, P=0.011) and FIB-4 (OR=2.3, P=0.01) were associated with greater risk of liver fibrosis in chronic hepatitis B patients. FIB-4 (OR=6.04, P=0.005) was a risk factor for liver fibrosis in HBeAg-positive patients. FIB-4 (OR=2.371, P=0.015) and GPR (OR=33.78, P=0.003) were liver fibrosis risk factor in HBeAg-negative patients. In chronic hepatitis C patients, GGT (OR=1.033, P=0.002), triglyceride (OR=−0.990, P=0.038) and FIB-4 (OR=3.499, P=0.006) showed statistical significances. The AUCs were 0.816 in FIB-4 (P<0.001) and 0.849 in GPR (P<0.001). CONCLUSIONS: FIB-4 and GPR may be useful blood markers for assessing liver fibrosis in chronic hepatitis B and hepatitis C patients. Further well-designed prospective study is required to validate these noninvasive blood markers in clinical practice.
Assuntos
Humanos , Área Sob a Curva , Bilirrubina , Biomarcadores , Plaquetas , Colesterol , DNA , Técnicas de Imagem por Elasticidade , Fibrose , Hepatite B , Hepatite B Crônica , Hepatite C , Hepatite C Crônica , Hepatite , Hepatite Crônica , Coeficiente Internacional Normatizado , Cirrose Hepática , Hepatopatias , Fígado , Linfócitos , Volume Plaquetário Médio , Neutrófilos , Contagem de Plaquetas , Estudos Prospectivos , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , Transferases , TriglicerídeosRESUMO
Progressive familial intrahepatic cholestasis (PFIC) is a group of severe genetic disorders, inherited in an autosomal recessive manner, causing cholestasis of hepatocellular origin, later progressing to biliary cirrhosis and liver failure. This is the first report of PFIC type 1 with novel compound heterozygous mutations in Korea. The patient was presented with intrahepatic cholestasis, a normal level of serum γ-glutamyl transferase, steatorrhea, and growth failure. Genetic testing of this patient revealed novel compound heterozygous mutations (p.Glu585Ter and p.Leu749Pro) in the ATP8B1 gene. After a liver transplantation at age 19 months, the patient developed severe post-transplant steatohepatitis.
Assuntos
Criança , Humanos , Colestase , Colestase Intra-Hepática , Fígado Gorduroso , Testes Genéticos , Coreia (Geográfico) , Cirrose Hepática Biliar , Falência Hepática , Transplante de Fígado , Esteatorreia , TransferasesRESUMO
BACKGROUND: Elevated serum alkaline phosphatase (AP) and γ-glutamyl transferase (γ-GT) are commonly observed in patients with acute pyelonephritis. The goal of this study was to examine the clinical significance of elevated serum AP and γ-GT levels and to explore the mechanisms underlying these changes. METHODS: We examined serum AP and γ-GT levels in 438 patients with acute pyelonephritis. Urine AP/creatinine (Cr), urine γ-GT/Cr, fractional excretion of AP, and fractional excretion of γ-GT (FE(γ-GT)) were evaluated in patients with elevated and normal serum levels. AP isoenzymes were also examined. RESULTS: We identified 77 patients (17.6%) with elevated serum AP and 134 patients (30.6%) with elevated serum γ-GT. Among them, both enzymes were elevated in 64 patients (14.6%). Older age, longer hospital stay, elevated baseline serum Cr, and complicated pyelonephritis were associated with increases in serum AP and γ-GT. Multivariate analysis showed that high serum AP levels were significantly correlated with renal impairment (odds ratio, 2.13; 95% confidence interval, 1.08–4.19; P = 0.029). FE(γ-GT) was significantly lower in patients with elevated serum enzyme levels. The liver fraction for AP isoenzyme profile did not increase in patients with elevated serum AP. CONCLUSION: Our results demonstrated that elevated serum AP and γ-GT levels are associated with complicated pyelonephritis and renal impairment. Lower FE(γ-GT) levels in patients with elevated serum enzymes may be the result of decreased urinary excretion of these enzymes.
Assuntos
Humanos , Fosfatase Alcalina , gama-Glutamiltransferase , Isoenzimas , Tempo de Internação , Fígado , Análise Multivariada , Pielonefrite , TransferasesRESUMO
PURPOSE: Lung adenocarcinoma (LA) is one of the major types of lung cancer. MicroRNAs (miRNAs) play an essential role in regulating responses of natural killer (NK) cells to cancer malignancy. However, the mechanism of miR-218-5p involved in the killing effect of NK cells to LA cells remains poorly understood. MATERIALS AND METHODS: The expression of miR-218-5p was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Serine hydroxymethyl transferase 1 (SHMT1) level was detected by qRT-PCR or western blots. Cytokines production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The killing effect of NK cells to LA cells was investigated using lactate dehydrogenase cytotoxicity assay kit. The interaction of miR-218-5p and SHMT1 was probed by luciferase activity assay. Xenograft model was established to investigate the killing effect of NK cells in vivo. RESULTS: miR-218-5p was enhanced and SHMT1 was inhibited in NK cells of LA patients, whereas stimulation of interleukin-2 (IL-2) reversed their abundances. Addition of miR-218-5p reduced IL-2-induced cytokines expression and cytotoxicity in NK-92 against LA cells. Moreover, SHMT1 was negatively regulated by miR-218-5p and attenuated miR-218-5p-mediated effect on cytotoxicity, IFN-γ and TNF-α secretion in IL-2-activated NK cells. In addition, miR-218-5p exhaustion inhibited tumor growth by promoting killing effect of NK cells. CONCLUSION: miR-218-5p suppresses the killing effect of NK cells to LA cells by targeting SHMT1, providing a potential target for LA treatment by ameliorating NK cells function.
Assuntos
Humanos , Adenocarcinoma , Western Blotting , Citocinas , Ensaio de Imunoadsorção Enzimática , Xenoenxertos , Homicídio , Interleucina-2 , Células Matadoras Naturais , L-Lactato Desidrogenase , Luciferases , Neoplasias Pulmonares , Pulmão , MicroRNAs , Necrose , Reação em Cadeia da Polimerase em Tempo Real , Serina , TransferasesRESUMO
This study investigated advantages and potential risks associated with drinking alcohol in Koreans based on the alcohol flush reaction. Our investigation reviewed published studies and examined moderate-drinking levels for Koreans based on modified National Institute on Alcohol Abuse and Alcoholism guidelines. Fourteen articles out of a total 198 publications were searched using PubMed, EMBASE, KoreaMed, and RISS (Research Information Sharing Service) databases and selected for review. Individuals without alcohol flush reaction (non-flushers) exhibited lower risks associated with insulin resistance, metabolic syndrome, and hyperhomocysteinemia and their 10-year cardiovascular disease risk when alcohol consumption was ≤8 drinks/wk. Conversely, risks associated with insulin resistance, metabolic syndrome, high blood pressure, prediabetes or type-2 diabetes, and high intraocular pressure and increases in carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels were present when >8 drinks were consumed. For individuals with flushing reaction (flushers), advantages were reported in relation to risks of hyperhomocysteinemia when alcohol consumption was ≤4 drinks/wk, whereas consumption of >4 drinks/wk increased the risk of insulin resistance, metabolic syndrome, high blood pressure, pre-diabetes or type-2 diabetes, high-risk colorectal adenoma, and high intraocular pressure and increased carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels. The moderate drinking level for Koreans is ≤8 drinks/wk for men aged ≤65 years and ≤4 drinks/wk for men aged over 65. For women, these limits should be half of those for men. Furthermore, individuals with flushing reaction should maintain an alcohol consumption level half of that for non-flushers.
Assuntos
Feminino , Humanos , Masculino , Adenoma , Consumo de Bebidas Alcoólicas , Glicemia , Doenças Cardiovasculares , Ingestão de Líquidos , Rubor , Hiper-Homocisteinemia , Hipertensão , Disseminação de Informação , Resistência à Insulina , Pressão Intraocular , Estado Pré-Diabético , Transferases , TransferrinaRESUMO
BACKGROUND: The blood level of alanine aminotransferase (ALT) is associated with increased coronary heart disease (CHD) risk. However, its use as an independent factor for CHD risk prediction remains unclear in Asian populations. The purpose of this study was to examine the association between serum ALT levels and CHD risk in Koreans. METHODS: This was a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011). The ALT levels of 3,215 individuals were analyzed. The Framingham Risk Score (FRS) modified by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) was used to compute the 10-year CHD risk prediction. RESULTS: Positive correlations were established between log-transformed ALT concentration and FRS (r=0.433, P<0.001). After adjusting for body mass index, low-density lipoprotein cholesterol, the amount of alcohol intake, and gamma-glutamyl transferase, the odds ratio (95% confidence interval) for intermediate or greater risk of 10- year CHD prediction (10-year risk ≥10%) for the lowest quartile of participants was 2.242 (1.405–3.577) for the second quartile, 2.879 (1.772–4.679) for the third quartile, and 3.041 (1.789–5.170) for the highest quartile. CONCLUSION: In Koreans, a higher serum ALT concentration was significantly correlated with 10-year CHD risk prediction according to NCEP ATP III guidelines.
Assuntos
Adulto , Humanos , Trifosfato de Adenosina , Alanina Transaminase , Alanina , Povo Asiático , Índice de Massa Corporal , Colesterol , Doença das Coronárias , Estudos Transversais , Educação , Coreia (Geográfico) , Lipoproteínas , Inquéritos Nutricionais , Razão de Chances , Fatores de Risco , TransferasesRESUMO
To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly β-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-keto-acid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other K(ATP) channel openers.
Assuntos
Acetil-CoA C-Acetiltransferase , Apoptose , Cálcio , Linhagem Celular , Coenzima A , Expressão Gênica , Metabolismo , Miócitos Cardíacos , Nicorandil , Espécies Reativas de Oxigênio , TransferasesRESUMO
To date, hematopoietic stem cell transplantation (HSCT) is the only choice of therapy for most patients with juvenile myelomonocytic leukemia (JMML). Relapse remains a major problem. Approximately 90% of patients carry either somatic or germline mutations of genes participating in RAS signal transduction such as PTPN11, CBL, K-RAS, N-RAS, or NF1 in their leukemic cells, allowing an understanding of the molecular pathophysiology of JMLL and the development of novel drugs. As these genetic aberrations are mutually exclusive, the genetic change observed in JMML helps us to establish the diagnosis of JMML. Furthermore, the genetic abnormalities of JMML are an important prognostic factor, as the type of abnormality may determine disease progression. Recent studies have revealed a strong association between hypermethylation of some genes and already known poor prognostic factors such as older age, elevated fetal hemoglobin at diagnosis, and somatic mutation of PTPN11. These molecular characteristics may be the basis for a guideline to determine the treatment, especially when to proceed with HSCT. Recently, novel drugs have been used based on these molecular characteristics. 5-Azacitidine, an inhibitor of DNA methyltransferase and tipifarnib, a selective farnesyl transferase inhibitor, have been used to improve the outcome of JMML. In addition, drugs which inhibit the RAS signal transduction have been developed, which are less toxic and will improve outcome in the near future.
Assuntos
Humanos , Diagnóstico , Progressão da Doença , DNA , Hemoglobina Fetal , Mutação em Linhagem Germinativa , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil , Recidiva , Transdução de Sinais , TransferasesRESUMO
BACKGROUND: A diabetes risk score in Korean adults was developed and validated. METHODS: This study used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) of 359,349 people without diabetes at baseline to derive an equation for predicting the risk of developing diabetes, using Cox proportional hazards regression models. External validation was conducted using data from the Korean Genome and Epidemiology Study. Calibration and discrimination analyses were performed separately for men and women in the development and validation datasets. RESULTS: During a median follow-up of 10.8 years, 37,678 cases (event rate=10.4 per 1,000 person-years) of diabetes were identified in the development cohort. The risk score included age, family history of diabetes, alcohol intake (only in men), smoking status, physical activity, use of antihypertensive therapy, use of statin therapy, body mass index, systolic blood pressure, total cholesterol, fasting glucose, and γ glutamyl transferase (only in women). The C-statistics for the models for risk at 10 years were 0.71 (95% confidence interval [CI], 0.70 to 0.73) for the men and 0.76 (95% CI, 0.75 to 0.78) for the women in the development dataset. In the validation dataset, the C-statistics were 0.63 (95% CI, 0.53 to 0.73) for men and 0.66 (95% CI, 0.55 to 0.76) for women. CONCLUSION: The Korean Diabetes Risk Score may identify people at high risk of developing diabetes and may be an effective tool for delaying or preventing the onset of condition as risk management strategies involving modifiable risk factors can be recommended to those identified as at high risk.