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  • 1
    In: International Journal of Cancer, Wiley, Vol. 149, No. 7 ( 2021-10), p. 1421-1425
    Abstract: In observational studies of children and adolescents, higher body weight has been associated with distinct disease outcomes, including cancer, in adulthood. Therefore, we performed a two‐sample Mendelian randomization (MR) study to evaluate the causal effect of childhood obesity on long‐term cancer risk. Single‐nucleotide polymorphisms associated with higher childhood body mass index (BMI) from large‐scale genome‐wide association studies were used as genetic instruments. Summary‐level data for 24 site‐specific cancers were obtained from UK Biobank. We found that a 1‐SD increase in childhood BMI (kg/m 2 ) was significantly associated with a 60% increase in risk of pancreatic cancer (odds ratio [OR]: 1.60; 95% confidence interval [CI] : 1.12‐2.28; P   〈  0.01) and a 47% increase in risk of esophageal cancer (OR: 1.47; 95% CI: 1.09‐1.97; P   〈  0.01) in adults. In contrast, there was an inverse association of genetic predisposition to childhood obesity with throat (OR: 0.46; 95% CI: 0.27‐0.79; P   〈  0.01) and breast cancer (OR: 0.77; 95% CI: 0.64‐0.94; P   〈  0.01) in adult life. For the other 20 cancers studied, no statistically significant association was observed. Our MR analyses found causal effects of childhood obesity on several cancers. Maintaining a healthy weight should be emphasized during childhood and adolescence to prevent cancer risk later in life.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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    detail.hit.zdb_id: 1474822-8
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  • 2
    In: Research, American Association for the Advancement of Science (AAAS), Vol. 2020 ( 2020-01)
    Abstract: The recent outbreak of COVID-19 has been rapidly spreading on a global scale. To date, there is no specific vaccine against the causative virus, SARS-CoV-2, nor is there an effective medicine for treating COVID-19, thus raising concerns with respect to the effect of risk factors such as clinical course and pathophysiological parameters on disease severity and outcome in patients with COVID-19. By extracting and analyzing all available published clinical data, we identified several major clinical characteristics associated with increased disease severity and mortality among patients with COVID-19. Specifically, preexisting chronic conditions such as hypertension, cardiovascular disease, chronic kidney disease, and diabetes are strongly associated with an increased risk of developing severe COVID-19; surprisingly, however, we found no correlation between chronic liver disease and increased disease severity. In addition, we found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality. Given the high risk of comorbidity and the high mortality rate associated with tissue damage, organ function should be monitored closely in patients diagnosed with COVID-19, and this approach should be included when establishing new guidelines for managing these high-risk patients. Moreover, additional clinical data are needed in order to determine whether a supportive therapy can help mitigate the development of severe, potentially fatal complications, and further studies are needed to identify the pathophysiology and the mechanism underlying this novel coronavirus-associated infectious disease. Taken together, these findings provide new insights regarding clinical strategies for improving the management and outcome of patients with COVID-19.
    Type of Medium: Online Resource
    ISSN: 2639-5274
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
    detail.hit.zdb_id: 2949955-0
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  • 3
    In: Advanced Science, Wiley, Vol. 10, No. 13 ( 2023-05)
    Abstract: Ferroptosis has been linked to the pathogenesis of hepatic injury induced by ischemia/reperfusion (I/R). However, the mechanistic basis remains unclear. In this study, by using a mouse model of hepatic I/R injury, it is observed that glutathione (GSH) and cysteine depletion are associated with deficiency of the reducing power of nicotinamide adenine dinucleotide phosphate (NADPH). Genes involved in maintaining NADPH homeostasis are screened, and it is identified that I/R‐induced hepatic ferroptosis is significantly associated with reduced expression and activity of NADP + ‐dependent malic enzyme 1 (Me1). Mice with hepatocyte‐specific Me1 gene deletion exhibit aggravated ferroptosis and liver injury under I/R treatment; while supplementation with L‐malate, the substrate of ME1, restores NADPH and GSH levels and eventually inhibits I/R‐induced hepatic ferroptosis and injury. A mechanistic study further reveals that downregulation of hepatic Me1 expression is largely mediated by the phosphatase and tensin homologue (PTEN)‐dependent suppression of the mechanistic target of rapamycin/sterol regulatory element‐binding protein 1 (mTOR/SREBP1) signaling pathway in hepatic I/R model. Finally, PTEN inhibitor, mTOR activator, or SREBP1 over‐expression all increase hepatic NADPH, block ferroptosis, and protect liver against I/R injury. Taken together, the findings suggest that targeting ME1 may provide new therapeutic opportunities for I/R injury and other ferroptosis‐related hepatic conditions.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2808093-2
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  • 4
    In: Clinical Nutrition ESPEN, Elsevier BV, Vol. 57 ( 2023-10), p. 501-509
    Type of Medium: Online Resource
    ISSN: 2405-4577
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2816659-0
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Nutrition, Metabolism and Cardiovascular Diseases Vol. 30, No. 6 ( 2020-06), p. 1053-1055
    In: Nutrition, Metabolism and Cardiovascular Diseases, Elsevier BV, Vol. 30, No. 6 ( 2020-06), p. 1053-1055
    Type of Medium: Online Resource
    ISSN: 0939-4753
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2050914-5
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  • 6
    In: Food & Function, Royal Society of Chemistry (RSC), Vol. 13, No. 16 ( 2022), p. 8388-8398
    Abstract: Background : The preventive effects of probiotic supplementation against gestational diabetes mellitus (GDM) in pregnant women remain unclear. The objective of this review was to investigate the effect of probiotic supplementation on the profiles of glucose metabolism in pregnant women without diabetes. The published literature was retrieved and screened from PubMed, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang, and Cochrane Center Register of Controlled Trails up to April 1 st , 2021. Random controlled trials (RCTs) of probiotic supplementation on pregnant women without GDM were included. Results : 12 RCTs (2213 participants) were eligible for meta-analyses. Overall, probiotic supplementation significantly reduced GDM incidence (Risk Ratio (RR) = 0.62, 95% CI: 0.39–0.99), serum fasting blood glucose (FBG) (Mean Difference (MD) = −0.14 mmol L −1 ; 95% CI: −0.26 mmol L −1 , −0.01 mmol L −1 ), insulin concentration (MD = −1.91 pmol L −1 , 95% CI: −2.41 to −1.41), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD = −0.32 mmol L −1 ; 95% CI: −0.42 mmol L −1 , −0.22 mmol L −1 ), and Quantitative Insulin sensitivity Check Index (QUICKI) (MD = 0.02, 95% CI: 0.01,0.03) in pregnant women. Probiotic supplementation had no significant effects on the results of the oral glucose tolerance test (OGTT) (1 h OGTT, MD = −0.10, 95% CI: −0.30, 0.09; 2 h OGTT, MD = −0.06, 95% CI: −0.31, 0.20). Conclusion : This meta-analysis suggested that probiotic supplementation may lead to an improvement in glycemic control and reduction of GDM incidence in pregnant women.
    Type of Medium: Online Resource
    ISSN: 2042-6496 , 2042-650X
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2022
    detail.hit.zdb_id: 2578152-2
    SSG: 21
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  • 7
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Robotics Vol. 7, No. 66 ( 2022-05-25)
    In: Science Robotics, American Association for the Advancement of Science (AAAS), Vol. 7, No. 66 ( 2022-05-25)
    Abstract: Submillimeter-scale robots developed from shape memory alloys can be actuated by a laser to permit terrestrial locomotion.
    Type of Medium: Online Resource
    ISSN: 2470-9476
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 8
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. 2 ( 2017-08), p. 449-465
    Abstract: Ferroptosis is a recently identified iron‐dependent form of nonapoptotic cell death implicated in brain, kidney, and heart pathology. However, the biological roles of iron and iron metabolism in ferroptosis remain poorly understood. Here, we studied the functional role of iron and iron metabolism in the pathogenesis of ferroptosis. We found that ferric citrate potently induces ferroptosis in murine primary hepatocytes and bone marrow–derived macrophages. Next, we screened for ferroptosis in mice fed a high‐iron diet and in mouse models of hereditary hemochromatosis with iron overload. We found that ferroptosis occurred in mice fed a high‐iron diet and in two knockout mouse lines that develop severe iron overload ( Hjv–/– and Smad4Alb/Alb mice) but not in a third line that develops only mild iron overload ( Hfe –/– mice). Moreover, we found that iron overload–induced liver damage was rescued by the ferroptosis inhibitor ferrostatin‐1. To identify the genes involved in iron‐induced ferroptosis, we performed microarray analyses of iron‐treated bone marrow–derived macrophages. Interestingly, solute carrier family 7, member 11 ( Slc7a11 ), a known ferroptosis‐related gene, was significantly up‐regulated in iron‐treated cells compared with untreated cells. However, genetically deleting Slc7a11 expression was not sufficient to induce ferroptosis in mice. Next, we studied iron‐treated hepatocytes and bone marrow–derived macrophages isolated from Slc7a11–/– mice fed a high‐iron diet. Conclusion: We found that iron treatment induced ferroptosis in Slc7a11–/– cells, indicating that deleting Slc7a11 facilitates the onset of ferroptosis specifically under high‐iron conditions; these results provide compelling evidence that iron plays a key role in triggering Slc7a11‐mediated ferroptosis and suggest that ferroptosis may be a promising target for treating hemochromatosis‐related tissue damage. (H epatology 2017;66:449–465).
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1472120-X
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  • 9
    In: Journal of Pineal Research, Wiley, Vol. 70, No. 2 ( 2021-03)
    Abstract: Accumulating evidence demonstrates that ferroptosis may be important in the pathophysiological process of traumatic brain injury (TBI). As a major hormone of the pineal gland, melatonin exerts many beneficial effects on TBI, but there is no information regarding the effects of melatonin on ferroptosis after TBI. As expected, TBI resulted in the time‐course changes of ferroptosis‐related molecules expression and iron accumulation in the ipsilateral cortex. Importantly, we found that treating with melatonin potently rescued TBI induced the changes mentioned above and improved functional deficits versus vehicle. Similar results were obtained with a ferroptosis inhibitor, liproxstatin‐1. Moreover, the protective effect of melatonin is likely dependent on melatonin receptor 1B (MT2). Although ferritin plays a vital role in iron metabolism by storing excess cellular iron, its precise function in the brain, and whether it involves melatonin's neuroprotection remain unexplored. Considering ferritin H (Fth) is expressed predominantly in the neurons and global loss of Fth in mice induces early embryonic lethality, we then generated neuron‐specific Fth conditional knockout ( Fth ‐KO) mice, which are viable and fertile but have altered iron metabolism. In addition, Fth ‐KO mice were more susceptible to ferroptosis after TBI, and the neuroprotection by melatonin was largely abolished in Fth‐ KO mice. In vitro siFth experiments further confirmed the results mentioned above. Taken together, these data indicate that melatonin produces cerebroprotection, at least partly by inhibiting neuronal Fth‐ mediated ferroptosis following TBI, supporting the notion that melatonin is an excellent ferroptosis inhibitor and its anti‐ferroptosis provides a potential therapeutic target for treating TBI.
    Type of Medium: Online Resource
    ISSN: 0742-3098 , 1600-079X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2027992-9
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  • 10
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. 4 ( 2020-07-31), p. 486-501
    Abstract: Maintaining iron homeostasis is essential for proper cardiac function. Both iron deficiency and iron overload are associated with cardiomyopathy and heart failure via complex mechanisms. Although ferritin plays a central role in iron metabolism by storing excess cellular iron, the molecular function of ferritin in cardiomyocytes remains unknown. Objective: To characterize the functional role of Fth (ferritin H) in mediating cardiac iron homeostasis and heart disease. Methods and Results: Mice expressing a conditional Fth knockout allele were crossed with 2 distinct Cre recombinase-expressing mouse lines, resulting in offspring that lack Fth expression specifically in myocytes (MCK-Cre) or cardiomyocytes (Myh6-Cre). Mice lacking Fth in cardiomyocytes had decreased cardiac iron levels and increased oxidative stress, resulting in mild cardiac injury upon aging. However, feeding these mice a high-iron diet caused severe cardiac injury and hypertrophic cardiomyopathy, with molecular features typical of ferroptosis, including reduced glutathione (GSH) levels and increased lipid peroxidation. Ferrostatin-1, a specific inhibitor of ferroptosis, rescued this phenotype, supporting the notion that ferroptosis plays a pathophysiological role in the heart. Finally, we found that Fth-deficient cardiomyocytes have reduced expression of the ferroptosis regulator Slc7a11, and overexpressing Slc7a11 selectively in cardiomyocytes increased GSH levels and prevented cardiac ferroptosis. Conclusions: Our findings provide compelling evidence that ferritin plays a major role in protecting against cardiac ferroptosis and subsequent heart failure, thereby providing a possible new therapeutic target for patients at risk of developing cardiomyopathy.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467838-X
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