Autophagic dysfunction is observed in diabetes mellitus. Resveratrol has a beneficial effect on diabetic cardiomyopathy. Whether the resveratrol‐induced improvement in cardiac function in diabetes is ...via regulating autophagy remains unclear. We investigated the mechanisms underlying resveratrol‐mediated protection against heart failure in diabetic mice, with a focus on the role of sirtuin 1 (SIRT1) in regulating autophagic flux. Diabetic cardiomyopathy in mice was induced by streptozotocin (STZ). Long‐term resveratrol treatment improved cardiac function, ameliorated oxidative injury and reduced apoptosis in the diabetic mouse heart. Western blot analysis revealed that resveratrol decreased p62 protein expression and promoted SIRT1 activity and Rab7 expression. Inhibiting autophagic flux with bafilomycin A1 increased diabetic mouse mortality and attenuated resveratrol‐induced down‐regulation of p62, but not SIRT1 activity or Rab7 expression in diabetic mouse hearts. In cultured H9C2 cells, redundant or overactive H2O2 increased p62 and cleaved caspase 3 expression as well as acetylated forkhead box protein O1 (FOXO1) and inhibited SIRT1 expression. Sirtinol, SIRT1 and Rab7 siRNA impaired the resveratrol amelioration of dysfunctional autophagic flux and reduced apoptosis under oxidative conditions. Furthermore, resveratrol enhanced FOXO1 DNA binding at the Rab7 promoter region through a SIRT1‐dependent pathway. These results highlight the role of the SIRT1/FOXO1/Rab7 axis in the effect of resveratrol on autophagic flux in vivo and in vitro, which suggests a therapeutic strategy for diabetic cardiomyopathy.
•Precise qualitative and quantitative analysis of phospholipid molecular species.•258 phospholipid molecular species were characterized in 486 human milk samples.•Dynamic changes of classes and sub ...classes of phospholipid over time were analyzed.•Critical change of phospholipid profile between lactation periods were analyzed.
Phospholipids are critical for milk digestion and infant development. But the profile of phospholipid molecular species in human milk and its dynamic changes during the lactation period have never been reported. The present study elucidated precise qualitative and quantitative analysis of 258 phospholipid molecular species in 486 human milk samples. Phosphatidylcholine is the most abundant class, followed by phosphatidylserine, phosphatidylethanolamine and sphingomyelin as the second abundant class in different lactation period. The plasmalogens declined along the lactation period, and the polyunsaturated-phospholipids decreased after 10–15 days. The decrease of phosphatidylcholines and phosphatidylglycerols, and the increase of lysophosphatidylethanolamines and lysophosphatidylcholines are critical changes from 0 to 5 days to 10–15 days; increase of phosphatidylinositols, phosphatidylserines, lysophosphatidylethanolamines and lysophosphatidylcholines is the key changes from 10–15 days to 40–45 days; the decrease of most phospholipid molecular species is the characteristic change from 40–45 days to 200–240 days; and the phospholipid profile achieved stability after 200 days.
Background & Aims
Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 ...levels and HCC survival in a large prospective cohort.
Methods
825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer‐specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P‐trend = .014) and 1.48 (95% CI: 1.12, 1.97; P‐trend = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0 kg/m2, except for that stronger associations were observed in patients co‐occurred more than three metabolic disorder diseases (P‐interaction = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P‐trend = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P‐trend = .195) for LCSS.
Conclusions
Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism‐related prognostic biomarker for HCC.
The association between dietary Fe intake and diabetes risk remains inconsistent. We aimed to explore the association between dietary Fe intake and type 2 diabetes mellitus (T2DM) risk in middle-aged ...and older adults in urban China. This study used data from the Guangzhou Nutrition and Health Study, an on-going community-based prospective cohort study. Participants were recruited from 2008 to 2013 in Guangzhou community. A total of 2696 participants aged 40-75 years without T2DM at baseline were included in data analyses, with a median of 5·6 (interquartile range 4·1-5·9) years of follow-up. T2DM was identified by self-reported diagnosis, fasting glucose ≥ 7·0 mmol/l or glycosylated Hb ≥ 6·5 %. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI. We ascertained 205 incident T2DM cases during 13 476 person-years. The adjusted HR for T2DM risk in the fourth quartile of haem Fe intake was 1·92 (95 % CI 1·07, 3·46; Ptrend = 0·010), compared with the first quartile intake. These significant associations were found in haem Fe intake from total meat (HR 2·74; 95 % CI 1·22, 6·15; Ptrend = 0·011) and haem Fe intake from red meat (HR 1·86; 95 % CI 1·01, 3·44; Ptrend = 0·034), but not haem Fe intake from processed meat, poultry or fish/shellfish. The association between dietary intake of total Fe or non-haem Fe with T2DM risk had no significance. Our findings suggested that higher dietary intake of haem Fe (especially from red meat), but not total Fe or non-haem Fe, was associated with greater T2DM risk in middle-aged and older adults.
Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause ...major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods.
Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease.
In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.
Scope
The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving ...protein synthesis.
Methods and Results
Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN‐93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time‐dependent (p < 0.05). Ultrahigh‐performance liquid chromatography results show that betaine increases S‐adenosyl‐l‐methionine (SAM) via methionine cycle. SAM sensor—Samtor—overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex.
Conclusions
These observations indicate that betaine could promisingly promote protein synthesis to delay age‐related muscle loss.
Betaine is a methyl donor in methionine cycle. The present study shows that betaine increases SAM level thereby attenuating Samtor complex inhibition for mTORC1 signaling to delay age‐related muscle loss and promotes C2C12 cells differentiation. The findings of the study indicate that betaine is a promising nutrition input upstream mTORC1 signaling for the elderly to delay the age‐related muscle loss.
It has been demonstrated that Tongxinluo (TXL), a traditional Chinese medicine compound, improves ischemic heart disease in animal models via vascular endothelial growth factor (VEGF) and endothelial ...nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload-induced heart failure in mice and explore the possible mechanism of action.
Transverse aortic constriction (TAC) surgery was performed in mice to induce heart failure. Cardiac function was evaluated by echocardiography. Myocardial pathology was detected using hematoxylin and eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using transmission electron microscopy. Angiogenesis and oxidative stress levels were determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and malondialdehyde assay, respectively. Fetal gene expression was measured using real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve-week low- and high-dose TXL treatment following TAC improved cardiac systolic and diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and myocardial ultrastructure derangement. Importantly, TXL increased myocardial capillary density significantly and attenuated oxidative stress injury in failing hearts. Moreover, TXL upregulated cardiac nitrite content and the protein expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4 expression in mouse heart following TAC.
Our findings indicate that TXL protects against pressure overload-induced heart failure in mice. Activation of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of the failing heart.
Abstract
Background
The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum ...TMAO and incident type 2 diabetes in middle-aged and older adults.
Methods
This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40–75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs).
Results
We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86–2.91) μmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84–1.61), and 1.42 (95% CI: 1.03–1.96) (
P
-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001–0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (
P
-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR.
Conclusions
Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults.
Trial registration:
NCT03179657.
https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1
Accumulating evidence linked bisphenol A (BPA) exposure with several diseases and even premature death. We aimed to evaluate the association between BPA exposure and mortality in US adults from the ...National Health and Nutrition Examination Survey (NHANES, 2003–2016), and to explore whether an anti-inflammatory diet can mitigate the deleterious effect of BPA on mortality. A cohort study including 8142 adults was conducted. Of these, 4143 (50.2%) were men, with a weighted average age of 55.9 years. Urinary BPA was measured by the on-line solid phase extraction, coupled to high performance liquid chromatography and tandem mass spectrometry. Dietary Inflammatory Index (DII) score was calculated based on 28 available kinds of food parameters in NHANES. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and cancer mortality. After 75927 person-years of follow-up (median, 9.3 years; maximum, 17.1 years), BPA exposure and DII score were independently associated with all-cause mortality. The fully-adjusted HR (95% CI) in the high versus low levels of BPA was 1.33 (1.05–1.70) for all-cause mortality, and the anti-inflammatory versus pro-inflammatory category of DII was 0.70 (0.56–0.87). There was no significant interaction between BPA and DII (p = 0.200). However, an indication of combined effect was found that, participants in subgroups with low BPA exposure and concurrently with anti-inflammatory category of DII score had 53% significantly lower all-cause mortality. Our findings highlight the importance of another monitoring cycles of BPA exposure, and its long-term adverse effects on health, even though the US government had restricted its use nowadays. Besides, we provided a new perspective against the adverse health effect induced by BPA exposure, that future studies could explore the offset impact of other healthy dietary patterns on the deleterious effect of BPA on health outcomes.
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•BPA exposure was independently associated with all-cause mortality in US adults.•It is still necessary to monitor BPA exposure and its adverse effects nowadays.•Adherence to an anti-inflammatory diet may offset the effect of BPA on mortality.
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