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AIMS: To investigate in women with prior gestational diabetes mellitus (GDM), differences by ethnicity and socioeconomic status in the incidence of recurrent GDM, type 2 diabetes (T2D), hypertension, and depression. METHODS: This was a retrospective cohort study including 10,868 women diagnosed with GDM in the Clinical Practice Research Datalink (CPRD GOLD) between January 01, 2000 and November 05, 2018. Linked data were obtained for Hospital Episode Statistics and the Index of Multiple Deprivation. We estimated incidence rates and hazard ratios, by ethnicity and socioeconomic status. RESULTS: During a follow-up of 58,479 person years (mean (SD): 5.38 (3.67) years), the crude incidence was 9.67 (95 % confidence interval: 9.30-10.00) per 100 person years for recurrent GDM, 3.86 (3.70-4.02) for depression, 2.15 (2.03-2.27) for T2D and 0.89 (0.81-0.97) for hypertension. South Asian ethnicity was associated with an increased risk of T2D compared to White (adjusted hazard ratio: 1.65; 1.34-2.05) and Black ethnicity was associated with a greater risk of hypertension (2.93; 1.93-4.46). Black and South Asian ethnicity were associated with a reduced risk of depression compared to White: 0.23 (0.13-0.39) and 0.37 (0.29-0.46), respectively. Incidence rates were higher for all conditions with increasing deprivation level. CONCLUSIONS: The risk of health complications in women with a prior history of GDM differs by ethnicity and socio-economic status, suggesting the opportunity for targeted assessment in the years following pregnancy. These findings may inform future guidelines on screening for health outcomes in women with GDM.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Etnicidad , Clase Social , Humanos , Femenino , Embarazo , Diabetes Gestacional/epidemiología , Adulto , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/epidemiología , Estudios de Seguimiento , Etnicidad/estadística & datos numéricos , Incidencia , Depresión/epidemiología , Pronóstico , Hipertensión/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
With WHO announcing COVID-19 no longer as a public health emergency of international concern (PHEIC) on May 5, 2023, coupled with the fact that the majority of the countries of the world have dropped strict city lockdown or border closure, this perhaps signals the end of the COVID-19 crisis caused by the SARS-CoV-2 virus. However, the COVID-19 pandemic has resulted in far-reaching effects affecting nearly every aspect of our lives and society. Notably, the food industry including agriculture, food manufacturers, food logistics, distributors and retailers have all felt the profound impact and had experienced significant stress during the pandemic. Therefore, it is essential to retrospect the lessons that can be learned from this pandemic for the food industry. This short review aims to address the food safety issues related to the COVID-19 pandemic by focusing on its foodborne transmission potential, innovations of virus detection strategies suitable for food industry; development of phathogenicaidal methods and devices to inactivate SARS-CoV-2 virus (particularly in industrial scale); and the set-up of related food regulations and guidelines as preventive and control measures for preventing the spread of SARS-CoV-2 virus through the food supply chain during the pandemic. This article may provide useful references for the food industry to minimize the food safety impact of COVID-19 (as well as other respiratory virus) and allows them to better prepare for similar future challenges.
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In the current study, the DNase-like activity of the Dawson-type polyoxometalate K6[P2Mo18O62] was explored. The obtained findings demonstrated that K6[P2Mo18O62] could effectively cleave phosphoester bonds in the DNA model substrate (4-nitrophenyl phosphate) and result in the degradation of plasmid DNA. Moreover, the application potential of this Dawson-type polyoxometalate as a DNase-mimetic artificial enzyme to degrade extracellular DNA (eDNA) in Escherichia coli (E. coli) bacterial biofilm was explored. The results demonstrated that K6[P2Mo18O62] exhibited high cleavage ability toward eDNA secreted by E. coli and thus eradicated the bacterial biofilm. In conclusion, Dawson-type polyoxometalate K6[P2Mo18O62] possessed desirable DNase-like activity, which could serve as a bacterial biofilm eradication agent by cleaving and degrading eDNA molecules.
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Foodborne diseases caused by foodborne pathogens pose risks to food safety. Effective detection and efficient inactivation of pathogenic bacteria has always been a research hotspot in the field of food safety. Complicating these goals, bacteria can be induced to adopt a viable but non-culturable (VBNC) state under adverse external environmental stresses. When in the VBNC state, pathogens cannot form visible colonies during traditional culture but remain metabolically active and toxic. The resulting false negative results in growth-related assays can jeopardize food safety. This review summarizes the latest research on VBNC foodborne pathogens, including induction conditions, detection methods, mechanism of VBNC formation, and possible control strategies. It is hoped that this review can provide ideas and methods for future research on VBNC foodborne pathogenic bacteria.
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Background: The worldwide prevalence of paternal perinatal anxiety (PPA) ranges between 3.4% and 25.0% antenatally, and 2.4% and 51.0% postnatally. Experiencing PPA can adversely impact the individual, partners, and infants. Research concerning PPA is lagging and fragmented compared to research for new mothers. Objectives: To establish the effectiveness of prevention or treatment interventions for PPA in adults identifying as male. Data sources: We completed searches of Medline, EMBASE, PsycINFO and Web of Science from inception to 2 December 2021, as well as hand searches of references from relevant papers. Search selection and data extraction: Randomised controlled trials delivering prevention or treatment interventions and reporting anxiety outcomes for new/expectant fathers in the perinatal mental health period were included. Our review follows the PRISMA reporting guidelines. One reviewer independently screened 5170 titles/abstracts; second reviewers screened 50%. Two reviewers independently screened full text, extracted data, and conducted risk of bias assessments. Synthesis: Cochrane's collaboration tool 2 was used to assess quality. Primarily results are synthesised narratively, a post-hoc sub-group analysis was completed on four studies using the same outcome measure. Main results: Twelve of the 5170 studies fulfilled the inclusion criteria. Studies used psychoeducational or practical skills interventions. Interventions mostly involved couple-dyads and three studies assessed PPA as a primary outcome. Included interventions were prevention-based; no treatment interventions were found. Father-only interventions consistently reported a significant reduction of PPA. Conclusions: Systematic searching yielded no treatment interventions, highlighting a substantial gap in the evidence base. Within a limited and heterogenous sample, no studies targeted diagnosed PPA. Evidence suggested father-focused interventions may be effective in preventing PPA, regardless of the intervention delivery mode or intervention content. However, consistency between study design and options within the field are lacking compared to interventions available for mothers.
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Escherichia coli (E. coli) is a common pathogen that causes diarrhea in humans and animals. In particular, E. coli can easily form biofilm on the surface of living or non-living carriers, which can lead to the cross-contamination of food. This review mainly summarizes the formation process of E. coli biofilm, the prevalence of biofilm in the food industry, and inhibition methods of E. coli biofilm, including chemical and physical methods, and inhibition by bioactive extracts from plants and animals. This review aims to provide a basis for the prevention and control of E. coli biofilm in the food industry.
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Chlorella has been identified as a rich source of unsaturated fatty acids. Since the antiobesity effects of unsaturated fatty acids have been well documented; therefore, we explored the antiobesity actions of chlorella unsaturated fatty acids (C.UFAs) in the current study. The obtained results demonstrated C.UFAs, which contain abundant linoleic acid, could retard body weight gain (reducing body weigh by 13.93% after 16 weeks of treatment), improve blood glucose (19.29% lower) and lipid profile (23.45% lower in TG, 8.76% lower in TC) compared to high-fat diet-fed C57BL/6J mice. The possible underlying mechanisms might involve reducing hepatic lipid accumulation via down-regulation of lipogenic genes (PPARγ, C/EBPα, LPL, aP2, FAS, and SREBP-1c) and up-regulation of lipolytic gene (adiponectin). We also demonstrate C.UFAs could reduce HFD-induced adipocyte hypertrophy via activation of AMPK signaling pathway in adipose tissue and liver. In summary, our study highlights the potential of C.UFAs as a functional food for obesity management. PRACTICAL APPLICATION: Chlorella has already been commercialized as a functional food antiobesity function. In the current study, the unsaturated fatty acids isolated from chlorella were found to exert beneficial effects on hyperglycemia, hyperlipidemia, hepatic steatosis, and adipocyte hypertrophy in high-fat diet-fed mice. This may provide theoretical foundation for developing novel chlorella-based functional foods.
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Chlorella , Dieta Alta en Grasa , Animales , Chlorella/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Ácidos Grasos Insaturados/farmacología , Hipertrofia/metabolismo , Lípidos/farmacología , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/metabolismoRESUMEN
AIMS: To estimate rates and identify determinants of post-partum glucose screening attendance in women with a history of gestational diabetes mellitus (GDM). METHODS: Retrospective cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify women diagnosed with GDM between 01/01/2000 and 05/11/2018. Age adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models. RESULTS: In 10,868 women with GDM, with an average follow-up of 5.38 years (95% CI 5.31,5.45), there was an average of 3.79 (95% CI 3.70,3.89) screening episodes per individual, with a mean time to first screening test of 1.22 (95% CI 1.18, 1.25) years. South Asian women had a significantly greater likelihood of being screened compared to White women within the first 5 years post-partum, aOR: 1.89 95% CI (1.20,2.98). A low proportion of women received at least one test per year of follow-up (23.87%). Older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were all associated with a greater likelihood of being screened. CONCLUSION: While the majority of women with previous GDM receive at least one glucose screening test within the first 5 years post-partum, fewer than a quarter of them receive on average one test per year of follow-up. Developing strategies to motivate more women to attend screening in primary care is essential.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/epidemiología , Etnicidad , Femenino , Glucosa , Humanos , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is an emerging opportunistic pathogen, which can cause bacterial skin diseases such as green nail syndrome, interdigital infections and folliculitis. Curcumin-mediated antimicrobial photodynamic therapy (aPDT) has been demonstrated as a promising therapeutic option for the treatment of skin infection though its inactivation of gram-negative bacteria such as P. aeruginosa. MATERIALS AND METHODS: In the present study, we examined the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT against P. aeruginosa. P. aeruginosa was treated with curcumin in the presence of 0.1-0.5 mg/L polymyxin B and irradiated by blue LED light (10 J/cm2). Bacterial cultures treated with curcumin alone served as controls. Colony forming units (CFU) were counted and the viability of P. aeruginosa was calculated after aPDT treatment. The possible underlying mechanisms for the enhanced killing effects were also explored. RESULTS: The killing effects of curcumin-mediated aPDT against P. aeruginosa was significantly enhanced by polymyxin B (over 2-log reductions). Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation. DISCUSSION: The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.
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Curcumina , Fotoquimioterapia , Antibacterianos/farmacología , Curcumina/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Polimixina B/farmacología , Pseudomonas aeruginosaRESUMEN
Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population.
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BACKGROUND: Gestational Diabetes Mellitus (GDM) is the most prevalent metabolic disorder during pregnancy, however, the association between dyslipidaemia and GDM remains unclear. METHODS: We searched Medline, Scopus, Web of Science, Cochrane, Maternity and Infant Care database (MIDIRS) and ClinicalTrials.gov up to February 2021 for relevant studies which reported on the circulating lipid profile during pregnancy, in women with and without GDM. Publications describing original data with at least one raw lipid [triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or very low-density lipoprotein cholesterol (VLDL-C)] measurement were retained. Data extraction was performed using a piloted data extraction form. The protocol was registered with PROSPERO (CRD42019139696). FINDINGS: A total of 292 studies, comprising of 97,880 pregnant women (28232 GDM and 69,648 controls) were included. Using random-effects meta-analysis models to pool study estimates, women with GDM had significantly higher (by 20%) TG levels, with a pooled weighted mean difference between GDM and non-GDM pregnancies of 0.388 mM (0.336, 0.439, p < 0.001). Further analyses revealed elevated TG levels occur in the first trimester and persist afterwards. Meta-regression analyses showed that differences in TG levels between women with GDM and healthy controls were significantly associated with age, BMI, study continent, OGTT procedure, and GDM diagnosis criteria. INTERPRETATION: Elevated lipids, particularly, TG, are associated with GDM.
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To overcome the poor water solubility of curcumin, a curcumin-ß-cyclodextrin (Cur-ß-CD) complex was prepared as a novel photosensitizer. Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to verify the formation of Cur-ß-CD. Furthermore, the ROS generation capacity and photodynamic bactericidal effect were measured to confirm this Cur-ß-CD complex kept photodynamic activity of curcumin. The result showed Cur-ß-CD could effectively generate ROS upon blue-light irradiation. The plate count assay demonstrated Cur-ß-CD complex possess desirable photodynamic antibacterial effect against food-borne pathogens including Staphylococcus aureus, Listeria monocytogenes and Escherichia coli. The cell morphology determined by scanning electron microscope (SEM) and transmission electron microscope (TEM) showed Cur-ß-CD could cause cell deformation, surface collapse and cell structure damage of the bacteria, resulting in the leakage of cytoplasmic; while agarose gel electrophoresis and SDS-PAGE further illustrated the inactivation mechanisms by Cur-ß-CD involve bacterial DNA damage and protein degradation.
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Antibacterianos/química , Curcumina/química , Fármacos Fotosensibilizantes/química , beta-Ciclodextrinas/química , Antibacterianos/farmacología , Rastreo Diferencial de Calorimetría , Curcumina/farmacología , Escherichia coli/efectos de los fármacos , Luz , Listeria monocytogenes/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Difracción de Rayos X , beta-Ciclodextrinas/farmacologíaAsunto(s)
Sistema del Grupo Sanguíneo ABO , COVID-19/sangre , Complicaciones Infecciosas del Embarazo/sangre , SARS-CoV-2/aislamiento & purificación , Pueblo Asiatico/etnología , Población Negra/etnología , COVID-19/etnología , COVID-19/virología , Ciudades , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/etnología , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2/fisiología , Reino Unido , Población Blanca/etnologíaRESUMEN
OBJECTIVE: To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. RESULTS: This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P<0.001). In populations of women with previous GDM, the cumulative incidence of T2DM was 16.46% (95% confidence interval 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. These differences were not statistically significant between subgroups (white v mixed populations, P=0.26; white v non-white populations, P=0.54). Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up. CONCLUSIONS: Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019123079.
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Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/fisiopatología , Diabetes Mellitus Tipo 2/etiología , Diabetes Gestacional/etiología , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Periodo Posparto , Embarazo , Factores de RiesgoAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Complicaciones Cardiovasculares del Embarazo , Embarazo en Diabéticas , Trombosis , Adulto , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Resultado Fatal , Femenino , Humanos , Neumonía Viral/sangre , Neumonía Viral/complicaciones , Neumonía Viral/tratamiento farmacológico , Embarazo , Complicaciones Cardiovasculares del Embarazo/sangre , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Embarazo en Diabéticas/sangre , SARS-CoV-2 , Trombosis/sangre , Trombosis/tratamiento farmacológico , Trombosis/etiología , Reino UnidoRESUMEN
Polycystic ovary syndrome (PCOS) is a risk factor for dysglycemia, insulin resistance, and type 2 Diabetes Mellitus (T2DM). Inefficient energy oxidation, metabolic inflexibility, is a marker of blunted metabolism. We conducted a systematic review on metabolic inflexibility in women with PCOS. We searched MEDLINE, EMBASE and Cochrane central (inception-October 2018) for studies evaluating metabolic inflexibility and reporting on changes in Respiratory Quotient (ΔRQ). We extracted data and assessed quality using The Newcastle-Ottawa Scale. We included five prospective cohort studies (461 women). Three compared PCOS women to unaffected subjects, one to women with obesity or T2DM, and one to adolescent girls; all had medium quality. Three studies showed higher metabolic inflexibility in women with PCOS (ΔRQ range 0.05-0.098) compared to unaffected subjects. Women with PCOS had similar metabolic inflexibility compared to those with T2DM (ΔRQ 0.05 ± 0.03 vs 0.06 ± 0.04, p = .98) and obesity (p = .06). Inflexibility was higher in hyperandrogenemic women with PCOS (ΔRQ 0.091 ± 0.060 vs 0.120 ± 0.010, p = .014). ΔRQ was lower in PCOS women with insulin resistance vs those with normal insulin sensitivity (0.04 ± 0.02 vs. 0.07 ± 0.04, p = .007). In conclusion, women with polycystic ovary syndrome appear to have higher metabolic inflexibility associated with hyperandrogenemia and insulin resistance.
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Resistencia a la Insulina/fisiología , Síndrome del Ovario Poliquístico/epidemiología , Síndrome del Ovario Poliquístico/metabolismo , Adolescente , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/epidemiología , Intolerancia a la Glucosa/metabolismo , Humanos , Hiperandrogenismo/complicaciones , Hiperandrogenismo/epidemiología , Hiperandrogenismo/metabolismo , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etiología , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Polyphenols are a class of plant secondary metabolites with a variety of physiological functions. Polyphenols and their intestinal metabolites could greatly affect host energy metabolism via multiple mechanisms. OBJECTIVE: The objective of this review was to elaborate the role of intestinal microecology in the regulatory effects of dietary polyphenols and their metabolites on energy metabolism. METHODS: In this review, we illustrated the potential mechanisms of energy metabolism regulated by the crosstalk between polyphenols and intestinal microecology including intestinal microbiota, intestinal epithelial cells, and mucosal immune system. RESULTS: Polyphenols can selectively regulate the growth of susceptible microorganisms (eg. reducing the ratio of Firmicutes to Bacteroides, promoting the growth of beneficial bacteria and inhibiting pathogenic bacteria) as well as alter bacterial enzyme activity. Moreover, polyphenols can influence the absorption and secretion of intestinal epithelial cells, and alter the intestinal mucosal immune system. CONCLUSION: The intestinal microecology play a crucial role for the regulation of energy metabolism by dietary polyphenols.
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The role of brown adipose tissue (BAT) in pathological states of energy homeostasis and impaired adipocyte function, such as obesity has been a major area of research interest in recent years. Herein, we sought to determine the direct effects of adipokines, visfatin and leptin on BAT thermogenesis. The effects of mouse recombinant visfatin, nicotinamide mononucleotide (NMN) and leptin with or without FK866 were studied on differentiated T37i cells. Treated cells were analyzed for key genes and proteins regulating BAT [UCP-1, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1α) and receptor-interacting protein 140 (RIP-140)] using quantitative PCR and western blot analysis. Data is presented as mean P-values. Both visfatin and leptin had significant concentration dependent effects on thermogenesis in brown pre-adipocytes and at physiological levels, increased uncoupling protein-1 (UCP-1) levels in brown adipocytes. These effects of visfatin were similar to that of nicotinamide mononucleotide (NMN), further strengthening the enzymatic role of visfatin. We also showed that leptin induced UCP-1 mRNA expression and protein production appears to be mediated by visfatin. High concentrations of both visfatin and leptin led to a dramatic decrease in UCP-1 protein levels, supporting the notion that visfatin levels are raised in obesity and that obese people have reduced BAT activity, plausibly through a reduction in UCP-1 levels. Additionally, we found differential regulation of key brown adipogenic genes, specifically, PRD1-BF1-RIZ1 homologous domain-containing 16 (PRDM-16), PPARgamma-coactivator-1alpha (PGC-1α) and receptor-interacting protein 140 (RIP-140) by visfatin. Our observations provide novel insights in the potential actions of visfatin in BAT.
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Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Citocinas/farmacología , Metabolismo Energético/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Nicotinamida Fosforribosiltransferasa/farmacología , Adipocitos Marrones/citología , Tejido Adiposo Pardo/citología , Animales , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Leptina/metabolismo , Leptina/farmacología , Ratones , Nicotinamida Fosforribosiltransferasa/metabolismoRESUMEN
Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR). In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, d-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific orexin receptor-1 (OX1R) antagonist (SB-408124) did not alter the responsiveness of OR-B. Treatment of the same model with OR-B resulted in a dose-dependent increase in myosin light chain and troponin-I (TnI) phosphorylation. Following ischaemia/reperfusion in the isolated Langendorff perfused rat heart model, OR-B, but not OR-A, exerts a cardioprotective effect; mirrored in an in vivo model as well. Unlike OR-A, OR-B was also able to induce extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2) and Akt phosphorylation in rat myocardial tissue and ERK1/2 phosphorylation in human heart samples. These findings were further corroborated in an in vivo rat model. In human subjects with heart failure, there is a significant negative correlation between the expression of OX2R and the severity of the disease clinical symptoms, as assessed by the New York Heart Association (NYHA) functional classification. Collectively, we provide evidence of a distinct orexin system in the heart that exerts a cardioprotective role via an OR-B/OX2R pathway.
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Cardiotónicos/farmacología , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Receptores de Orexina/agonistas , Orexinas/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Animales , Señalización del Calcio , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Preparación de Corazón Aislado , Masculino , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Cadenas Ligeras de Miosina/metabolismo , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Fosforilación , Embarazo , Ratas Wistar , Troponina I/metabolismoRESUMEN
Glucagon-like peptide 1 (GLP-1) levels may be reduced in type 2 diabetes, but whether a similar impairment exists in gestational diabetes mellitus (GDM) has not been established. We studied this in a prospective cohort study of pregnant women (n = 144) during oral glucose tolerance test (OGTT). GLP-1, glucose, and insulin were sampled at 30-min intervals during a 2-h 75-g OGTT, and indices of insulin secretion and sensitivity were calculated. In a nested case-control study, women with GDM (n = 19) had 12% lower total GLP-1 secretion area under the curve (AUC) compared with control subjects matched for age, ethnicity, and gestational age (n = 19), selected from within the lowest quartile of glucose120 min values in our cohort. GDM had lower GLP-1 response in the first 30 min (19% lower GLP-130 min and 17% lower AUC0-30 min) after adjustment for possible confounders. Their glucose levels began to diverge at 30 min of the OGTT with increasing insulin levels, and by 120 min, their insulin levels were three times higher. In a secondary cohort of 57 women that included "high-normal" glucose120 min values, low GLP-1 AUC0-30 min was independently associated with lower indices of insulin secretion and sensitivity. In conclusion, we have observed that women with GDM have lower GLP-1 response at 30 min of an OGTT and hyperglycemia at 120 min despite significant hyperinsulinemia.