RESUMO
Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Coenzima A Ligases/metabolismo , Coenzima A Ligases/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Ácidos Graxos/uso terapêutico , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ácido Oleico/metabolismo , Ácido Oleico/farmacologia , Ácido Oleico/uso terapêuticoRESUMO
Background: Non-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders. Methods: A total of 120 hospitalized adolescent patients with depressive disorders aged 14-24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders. Results: Compared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively. Conclusion: A combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.
RESUMO
OBJECTIVE: To observe the clinical efficacy of Chinese drugs combined with chemotherapy in the treatment of acute myeloid leukemia (AML) and to investigate the prognostic relevance of the main parameters in AML treated with integrative medicine. METHODS: Forty AML patients hospitalized at the authors hospital were treated with Chinese drugs and chemotherapy. The routine examination, immunophenotype and karyotype analyses were carried out. The clinical efficacy was observed and the prognostic factors were analyzed. RESULTS: (1) Clinical efficacy: Twenty patients had complete remission (CR), with the CR rate being 50.0%. Among these patients, the CR rate was 73.9% (17/23) in de novo AML and 17.6% (3/17) in secondary or refractory AML, respectively. The median disease free survival (DFS) was 6 months (2-32 months) and median overall survival (OS) was 7 months (1-36 months). (2) Analysis of prognostic factors: Aging (> 60 years) and hepatosplenomegaly or extramedullary leukemia did not affect the treatment outcome. Patients with lower white blood cell (WBC) counts (<4.0x10(9)/L) had a significantly higher CR rate (P<0.01). Secondary or refractory AML was associated with a lower CR rate and shorter OS (P<0.01,P<0.05). Expression of CD34 was an adverse factor for obtaining CR (P<0.05) and survival in both DFS and OS (P<0.05,P<0.01). The expression of CD56 was significantly associated with a lower CR rate (P<0.05), but did not affect DFS and OS. Twenty-three (57.5%) out of 40 cases had chromosomal abnormalities. The CR rate was decreased and both DFS and OS shortened stepwise from the cases with favorable cytogenetics to those with intermediate and unfavorable cytogenetics (P<0.01). CONCLUSIONS: The combined treatment of Chinese drugs with chemotherapy has a predominant effect in de novo AML. Secondary or refractory AML, expression of CD34 and CD56, and unfavorable cytogenetics were the main factors of poor prognosis in AML.