RESUMEN
Helicobacter pylori (H. pylori) infection remains a significant global public health problem. Vaccine, especially edible vaccine, is considered to be effective in the management of H. pylori infections. By using recombinant technology, Lactococcus lactis (L. lactis) could serve as an antigen-delivering vehicle for the development of edible vaccine. The aim of this study was to produce edible UreB (urease B) vaccine derived from L. lactis against H. pylori. The UreB subunit is the most effective and common immunogen of all strains of H. pylori. The UreB was produced as a chimeric protein fused with IL-2 (human interleukin 2) as the mucosal adjuvant. Mucosal immunization of mice with recombinant L. lactis NZ9000 containing the UreB-IL-2 protein elicited more anti-UreB antibody that specifically bounded to the purified bacterial UreB protein and more cytokines such as IFN-γ, IL-4, and IL-17, and had a lower H. pylori burden and urease activity than control mice. These results suggest that the recombinant L. lactis expressing UreB-IL-2 can be potentially used as an edible vaccine for controlling H. pylori infection.
Asunto(s)
Vacunas Bacterianas/administración & dosificación , Infecciones por Helicobacter/prevención & control , Helicobacter pylori/inmunología , Interleucina-2/inmunología , Ureasa/inmunología , Administración Oral , Animales , Anticuerpos Antibacterianos/biosíntesis , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/inmunología , Vacunas Bacterianas/inmunología , Citocinas/inmunología , Expresión Génica , Vectores Genéticos , Infecciones por Helicobacter/inmunología , Humanos , Interleucina-2/metabolismo , Lactococcus lactis/genética , Lactococcus lactis/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes de Fusión/inmunología , Ureasa/genética , Ureasa/metabolismo , Vacunas Comestibles/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
BACKGROUND: China has the largest number of patients with type 2 diabetes mellitus (T2DM) in the world. However, owing to insufficient knowledge of self-management in patients with diabetes, blood glucose (BG) control is poor. Most diabetes-related self-management applications fail to bring significant benefits to patients with T2DM because of the low use rate and difficult operation. OBJECTIVE: This study aims to examine the effectiveness of the combination of the self-designed web-based T2DM management software TangPlan and WeChat on fasting BG (FBG), glycated hemoglobin (HbA1c), body weight, blood pressure (BP), and lipid profiles in patients with T2DM over a 6-month period. METHODS: Participants were recruited and randomized into the TangPlan and WeChat or control groups. Participants in the control group received usual care, whereas the TangPlan and WeChat participants received self-management guidance with the help of TangPlan and WeChat from health care professionals, including BG self-monitoring; healthy eating; active physical exercise; increasing medication compliance; and health education during follow-ups, lectures, or web-based communication. They were also asked to record and send self-management data to the health care professionals via WeChat to obtain timely and effective guidance on diabetes self-management. RESULTS: In this study, 76.9% (120/156) of participants completed the 6-month follow-up visit. After the intervention, FBG (mean 6.51, SD 1.66 mmol/L; P=.048), HbA1c (mean 6.87%, SD 1.11%; P<.001), body weight (mean 66.50, SD 9.51 kg; P=.006), systolic BP (mean 127.03, SD 8.00 mm Hg; P=.005), diastolic BP (mean 75.25, SD 5.88 mm Hg; P=.03), serum low-density lipoprotein cholesterol (mean 2.50, SD 0.61 mmol/L; P=.006), and total cholesterol (mean 4.01, SD 0.83 mmol/L; P=.02) in the TangPlan and WeChat group were all significantly lower, whereas serum high-density lipoprotein cholesterol (mean 1.20, SD 0.25 mmol/L; P=.01) was remarkably higher than in those in the control group. Compared with the baseline data, significance was found in the mean change in FBG (95% CI -0.83 to -0.20; P=.002), HbA1c (95% CI -1.92 to -1.28; P<.001), body weight (95% CI -3.13 to -1.68; P<.001), BMI (95% CI -1.10 to -0.60; P<.001), systolic BP (95% CI -7.37 to -3.94; P<.001), diastolic BP (95% CI -4.52 to -2.33; P<.001), triglycerides (95% CI -0.16 to -0.03; P=.004), serum low-density lipoprotein cholesterol (95% CI -0.54 to -0.30; P<.001), and total cholesterol (95% CI -0.60 to -0.34; P<.001) in the TangPlan and WeChat group but not in the control group (P=.08-.88). CONCLUSIONS: Compared with usual care for patients with T2DM, the combination of TangPlan and WeChat was effective in improving glycemic control (decrease in HbA1c and BG levels) and serum lipid profiles as well as reducing body weight in patients with T2DM after 6 months. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000028843; https://tinyurl.com/559kuve6.
Asunto(s)
Diabetes Mellitus Tipo 2 , Automanejo , Diabetes Mellitus Tipo 2/terapia , Ejercicio Físico , Hemoglobina Glucada/análisis , Humanos , InternetRESUMEN
PURPOSE: Normal weight obesity (NWO), defined as normal body mass index (BMI) and excessive body fat percentage (BF%), has been shown to be associated with a significantly higher risk of developing metabolic syndrome, cardiometabolic dysfunction and with higher mortality. However, there is limited literature regarding the potential associations between NWO and lifestyles. This study aimed to investigate the associations of lifestyles with NWO in Chinese university students. PARTICIPANTS AND METHODS: A total of 279 university students with normal BMI were recruited and divided into NWO and normal weight non-obesity (NWNO) groups by BF%. Body composition and anthropometrics were measured, and participants were asked to finish the Healthy Lifestyle Scale for University Students (HLSUS) questionnaire. RESULTS: A total of 26 male (25.5%) and 71 female (40.1%) students were identified as NWO. Compared to NWNO students, body weight, BMI, body fat mass, visceral fat area, waist circumference and hip circumference of NWO students were all significantly higher both in male and female students (P < 0.05). The body fat mass, BF% and visceral fat area were significantly negatively correlated with the total HLSUS, physical exercise behavior, and dietary nutrition behavior scores in NWNO males, NWO and NWNO females (P < 0.05). The risk of NWO was lower in those students with higher scores in physical exercise behavior in both males (OR = 0.298, 95% CI = 0.121~0.733) and females (OR = 0.653, 95% CI = 0.505~0.843), while dietary nutrition behavior (OR = 0.759, 95% CI = 0.584~0.986) and stress management behavior (OR = 0.503, 95% CI = 0.335~0.755) decreased the risk of NWO only in females. CONCLUSION: The incidence of NWO was high among university students, especially in females, which might be related with unhealthy lifestyles. NWO university students should pay attention to lifestyle adjustments, especially physical exercise, dietary nutrition and stress management, for preventing the health risk in NWO.
RESUMEN
AIMS: The present study was designed to compare the effects of a low-fat diet (LF), calorie restriction (CR), quercetin (Que) and exercise (Ex) on hepatic steatosis in a high-fat (HF) diet-induced obesity prone (OP) model in the perspective of microRNA (miR)-dependent thyroid hormone (TH) synthesis and action. MAIN METHODS: Male C57BL/6J mice were administered a HF diet for 10 weeks to induce OP phenotype and then divided into 5 groups, HF diet (OP-HF), LF diet (OP-LF), 70% CR (OP-CR), 0.05% Que (OP-Que) and a treadmill exercise regimen (OP-Ex); one additional group fed LF diet served as control (LF). 7 weeks later, serum indexes, metabolic alterations, redox status and histological appearance in the thyroid and liver, and TH related miRs with their targets expressions were determined. KEY FINDINGS: No significance on T3 levels was observed among the six groups. LF, CR, Que and Ex significantly ameliorated HF-induced hepatic steatosis to varying degrees, inhibited T4 production via differentially elevating miR-339, miR-383 and miR-146b to decrease NIS expression and regulating miR-200a/Nrf2 to maintain redox status in the thyroid. Furthermore, these four interventions differentially and significantly decreased miR-383 and miR-146b to elevate TRb and DIO1 expression, and subsequent TH responsive lipid metabolism genes regulation. Among them, the effects of CR on hepatic steatosis were the most prominent. SIGNIFICANCE: Our data indicated that amelioration of hepatic steatosis by LF, CR, Que and Ex resulted in many shared, but also many differential changes in the miR-dependent TH production and action.
Asunto(s)
Dieta con Restricción de Grasas , Hígado Graso/terapia , MicroARNs/fisiología , Obesidad/complicaciones , Condicionamiento Físico Animal , Hormonas Tiroideas/metabolismo , Animales , Restricción Calórica , Hígado Graso/dietoterapia , Hígado Graso/etiología , Hipolipemiantes/uso terapéutico , Lípidos/análisis , Hígado/química , Masculino , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Estrés Oxidativo , Quercetina/uso terapéuticoRESUMEN
Hepatic microRNAs (miRs) regulate local thyroid hormone (TH) action and TH-related lipid metabolism. We previously found that myricetin effectively ameliorated hepatic steatosis by targeting PPAR signaling pathway, in which the differentially expressed genes were TH-responsive. The present study was designed to explore the mechanism by which myricetin regulated miR-dependent TH action and lipid metabolism on high-fat diet (HFD)-induced hepatic steatosis. C57BL/6J mice were fed a HFD with or without 100 mg kg-1 myricetin by oral gavage for 16 weeks (n = 8 for each group). The results showed that myricetin improved HFD-induced hepatic steatosis, increased serum TH levels and hepatic type 1 deiodinase (DIO1) activities, and elevated energy expenditure in relation to the HFD mice. Meanwhile, myricetin inhibited miR-205 and miR-146b up-regulation induced by HFD, and also up-regulated their targets, Dio1 and thyroid hormone receptor b (TRb) expression, at both the transcriptional and translational levels, accompanied by the regulation of TH responsive lipid metabolism genes. Overexpression or knockdown of miR-205 failed to affect Dio1 mRNA and protein levels in primary mouse hepatocytes. Myricetin directly decreased miR-146b expression in miR-146b mimic-treated hepatocytes to elevate TRb levels. However, the beneficial effects of myricetin on hepatic TH action and lipid metabolism were abolished by TRb siRNA in free fatty acid (FFA)-treated hepatocytes. Our results indicated that myricetin attenuated hepatic steatosis via the miR-146b/TRb pathway and should be considered for the management of NAFLD conditions.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Hígado Graso/tratamiento farmacológico , Flavonoides/farmacología , MicroARNs/metabolismo , Receptores beta de Hormona Tiroidea/metabolismo , Tejido Adiposo , Animales , Peso Corporal , Regulación de la Expresión Génica/efectos de los fármacos , Lípidos/sangre , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Receptores beta de Hormona Tiroidea/genéticaRESUMEN
Hepatic lipid accumulation and oxidative stress (OS) lead to non-alcoholic fatty liver disease (NAFLD). Thus, we hypothesized that antihyperlipidemic and antioxidant activities of niga-ichigoside F1 (NI) would ameliorate events leading to NAFLD. Lanbuzheng (Geum japonicum Thunb. var. chinense), a type of wild vegetable found in Southwest China, was used to extract NI. Male C57BL/6J mice were fed a standard diet (Con) or a high-fat diet (HFD) (denoted as diet) with or without 40 mg kg-1 NI (defined as treatment) for 12 weeks. Diet-treatment interactions were observed in the final body weight, fat pad mass, respiratory exchange ratio (RER) in the daytime, and energy expenditure during the whole day. Moreover, NI alleviated hepatic steatosis, possibly by significantly interacting with HFD to regulate lipid metabolism genes (including Srebp1c, Acc1, Fasn, Scd1, Cpt1a and Fabp5). We also found significant diet-treatment interactions on superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and thiobarbituric acid reactive substance (TBARS) levels, as well as the nuclear and cellular Nrf2 protein levels. Significant free fatty acid (FFA)-treatment interactions on Nrf2 nuclear translocation, antioxidant enzymes activities, genes in lipogenesis (Srebp1c, Acc1, Fasn, and Scd1), and fatty acid oxidation (Pparα) and transport (Fabp5 and Cd36) were also detected in 1 mM FFA-treated HepG2 cells with or without 20 µM NI. These beneficial effects of NI on oxidative stress and lipid accumulation were abolished by Nrf2 siRNA. Our data revealed that dietary NI could prevent HFD-induced hepatic steatosis, possibly via interacting with HFD to activate Nrf2 nuclear translocation to maintain a redox status, thus regulating lipid metabolism genes expressions.
Asunto(s)
Geum/química , Factor 2 Relacionado con NF-E2/genética , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Saponinas/administración & dosificación , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.
Asunto(s)
Antioxidantes/uso terapéutico , Suplementos Dietéticos , Modelos Animales de Enfermedad , Flavonoides/uso terapéutico , Regulación de la Expresión Génica , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Transporte Activo de Núcleo Celular , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Dieta Alta en Grasa/efectos adversos , Perfilación de la Expresión Génica , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Hígado/enzimología , Hígado/patología , Masculino , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , NAD(P)H Deshidrogenasa (Quinona)/química , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Oxidativo , PPAR gamma/antagonistas & inhibidores , PPAR gamma/genética , PPAR gamma/metabolismo , Peroxisomas/metabolismo , Peroxisomas/patología , Distribución Aleatoria , Transducción de SeñalRESUMEN
Hepatitis B x-interacting protein (HBXIP), a co-factor of survivin, was originally identified by its binding with the C-terminus of the hepatitis B virus x protein (HBx). We have recently shown that HBXIP promotes the growth of both normal liver cells and hepatoma cells in vitro, but the molecular mechanisms of this have not been documented. In this study, we investigated the potential effects of HBXIP on the proliferation of HepG2 cells and the intracellular signaling pathway mediating these changes. Over-expression of the HBXIP gene promoted the proliferation of HepG2 cells, as shown by the MTT assay. We also showed that HBXIP induced cellular accumulation in the S phase concomitantly with up-regulation of cyclinD(1) and down-regulation of p21 and p53 levels. Moreover, HBXIP over-expression cells showed activation of the PI3K/Akt pathway; this activation was accompanied by an increase in phosphorylation of glycogen synthase kinase 3ß. LY294002, a specific inhibitor of PI3K, blocked HBXIP-stimulated Akt phosphorylation and suppressed the cell cycle promotion induced by HBXIP in HepG2 cells. The increase in cyclinD(1) protein levels induced by HBXIP was inhibited when cells were incubated with LY294002. In conclusion, our data suggest that the proliferation of HepG2 cells promoted by HBXIP is associated with activation of the PI3K/Akt signaling pathway.