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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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Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/metabolismo , Adolescente , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Intolerância à Glucose/complicações , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/metabolismo , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/epidemiologia , Hiperandrogenismo/metabolismo , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Síndrome do Ovário Policístico/complicações , Adulto JovemRESUMO
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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Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Citocinas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/farmacologia , Adipócitos Marrons/citologia , Tecido Adiposo Marrom/citologia , Animais , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Leptina/metabolismo , Leptina/farmacologia , Camundongos , Nicotinamida Fosforribosiltransferase/metabolismoRESUMO
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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Cardiotônicos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Receptores de Orexina/agonistas , Orexinas/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Animais , Sinalização do Cálcio , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Preparação de Coração Isolado , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Cadeias Leves de Miosina/metabolismo , Receptores de Orexina/genética , Receptores de Orexina/metabolismo , Fosforilação , Gravidez , Ratos Wistar , Troponina I/metabolismoAssuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Complicações Cardiovasculares na Gravidez , Gravidez em Diabéticas , Trombose , Adulto , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Gravidez em Diabéticas/sangue , SARS-CoV-2 , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/etiologia , Reino UnidoRESUMO
OBJECTIVE: Adipolin/CTRP12 is a novel adipokine with anti-inflammatory and glucose-lowering properties in rodents. We sought to investigate the effects of metformin treatment (850 mg twice daily for 6 months) and a 2 h 75 g oral glucose tolerance test (OGTT) on serum adipolin concentrations in humans. DESIGN: Cross-sectional study [PCOS (n = 83) and control (n = 39) subjects]. Serum adipolin was measured by ELISA. Metformin treatment (850 mg twice daily for 6 months) was offered to all women with PCOS, 34 women participated but 21 women completed 6 months of metformin therapy. Reasons for subjects not completing the study were nausea and gastrointestinal side effects (n = 4), pregnancies (n = 5), noncompliance (n = 2) and loss of contact (n = 2). RESULTS: Metformin treatment (850 mg twice daily for 6 months) substantially increased serum adipolin concentrations (P < 0·05) in women with polycystic ovary syndrome (PCOS), a pro-inflammatory state associated with obesity, diabetes, dyslipidaemia and atherosclerosis. Furthermore, changes in waist-hip ratio, glucose, triglycerides, CRP and carotid intima media thickness showed significant negative associations with changes in adipolin levels (P < 0·05, P < 0·01); in multiple regression analyses, only changes in glucose were predictive of changes in adipolin levels (ß = -0·570, P = 0·009). Serum adipolin decreased significantly in response to the OGTT in PCOS and control subjects at 90 min (P < 0·05) and 120 min (P < 0·01). CONCLUSIONS: Adipolin and/or novel pharmacologic agents that increase adipolin's circulating concentrations might constitute a novel approach in the treatment of insulin resistant states.
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Adipocinas/sangue , Glicemia/metabolismo , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Obesidade/metabolismo , Síndrome do Ovário Policístico/metabolismo , Resultado do Tratamento , Relação Cintura-Quadril , Adulto JovemRESUMO
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 , Etnicidade , Classe Social , Humanos , Feminino , Gravidez , Diabetes Gestacional/epidemiologia , Adulto , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/epidemiologia , Seguimentos , Etnicidade/estatística & dados numéricos , Incidência , Depressão/epidemiologia , Prognóstico , Hipertensão/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
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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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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BACKGROUND/AIMS: Adiponectin levels are decreased in diabetes and atherosclerosis. Coexisting hyperglycaemia and systemic inflammation predisposes to dysregulated angiogenesis and vascular disease. We investigated the effect of globular adiponectin (gAd) and full-length adiponectin (fAd) on angiogenesis and pro-angiogenic molecules, i.e. matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF), in human microvascular endothelial cells (HMEC-1). METHODS: Angiogenesis was assessed by studying capillary tube formation in HMEC-1 on growth factor-reduced Matrigel. Endothelial cell migration assay was performed in a modified Boyden chamber. RESULTS: Endothelial cell proliferation, in vitro migration and angiogenesis were significantly increased by gAd (mediated by AdipoR1, AMPK-Akt pathways), and gAd significantly increased MMP-2, MMP-9 and VEGF expression levels. The effect of gAd on VEGF appears to be mediated by AdipoR1, whilst the effect of gAd on MMP-2 and MMP-9 appears to be mediated by AdipoR1 and AdipoR2. Only endothelial cell proliferation was significantly increased by fAd in human microvascular endothelial cells and appears to be mediated by AdipoR2. No significant effects on MMP-2, MMP-9 and VEGF were observed. Importantly, gAd decreased glucose and C-reactive protein-induced angiogenesis with a concomitant reduction in MMP-2, MMP-9 and VEGF in HMEC-1 cells. CONCLUSION: We report novel insights into the mechanisms of adiponectin on angiogenesis.
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Indutores da Angiogênese/farmacologia , Células Endoteliais/efeitos dos fármacos , Adiponectina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Fragmentos de Peptídeos/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
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/farmacologia , Curcumina/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polimixina B/farmacologia , Pseudomonas aeruginosaRESUMO
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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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/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/epidemiologia , Etnicidade , Feminino , Glucose , Humanos , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
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 Hiperlipídica , Animais , Chlorella/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/farmacologia , Hipertrofia/metabolismo , Lipídeos/farmacologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismoRESUMO
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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OBJECTIVE: The role of retinol-binding protein-4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender-specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender-specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4. RESEARCH DESIGN AND METHODS: The study is an ex-vivo prospective analysis of paired AT-samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m(2) , women: 38·4 ± 11kg/m(2) ) and homeostasis model assessment of insulin resistance taken during elective surgery and ex-vivo culture using visceral-AT (VAT)-explants (n = 10). Plasma RBP4 and cytokines were measured by ELISA and mRNA expression in AT by real-time PCR. VAT-explants were cultured with recombinant leptin and insulin and RBP4 determined by western blot analyses. RESULTS: Overall subcutaneous AT (SCAT)-RBP4 mRNA expression was higher than VAT-expression [3·1 ± 0·26 signal units (SU; mean ± SE) vs 1·79 ± 0·18SU, n = 48, P < 0·0001], but neither correlated with circulating RBP4. SCAT-RBP4 expression was higher in women and correlated with BMI (r =-0·5, P = 0·009) and fat mass (r= -0·5, P = 0·002). VAT-RBP4 correlated positively with GLUT-4 expression and adiponectin in men only (r= 0·54, P = 0·03 and r = 0·64, P < 0·002, respectively) when correcting for age and fat mass. Multiple regression determined leptin AT-expression as a positive predictor of AT-RBP4 in women (SCAT: ß = 0·50, P = 0·002; VAT: ß = 0·58, P = 0·003) and adiponectin for VAT-RBP4 in men (ß = 0·69; P=0·001). AT-RBP4 mRNA expression showed no relation with insulin resistance. Leptin stimulated RBP-4 secretion ex-vivo, whilst insulin did not affect RBP4. CONCLUSION: AT-derived RBP4-mRNA expression is gender specific and regulated by leptin. Circulating RBP4 levels appear to be independent of AT-RBP4 secretion.
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Tecido Adiposo/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adulto , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Transportador de Glucose Tipo 4/genética , Humanos , Gordura Intra-Abdominal/metabolismo , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Proteínas Plasmáticas de Ligação ao Retinol/genética , Fatores SexuaisRESUMO
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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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.
Assuntos
Antibacterianos/química , Curcumina/química , Fármacos Fotossensibilizantes/química , beta-Ciclodextrinas/química , Antibacterianos/farmacologia , Varredura Diferencial de Calorimetria , Curcumina/farmacologia , Escherichia coli/efeitos dos fármacos , Luz , Listeria monocytogenes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X , beta-Ciclodextrinas/farmacologiaRESUMO
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.