Browsing by Author "Dai, Qi"
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Item Author Correction: Magnesium intake and mortality due to liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort(Springer Nature, 2019-05-01) Wu, Lijun; Zhu, Xiangzhu; Fan, Lei; Kabagambe, Edmond K.; Song, Yiqing; Tao, Menghua; Zhong, Xiaosong; Hou, Lifang; Shrubsole, Martha J.; Liu, Jie; Dai, Qi; Epidemiology, School of Public HealthA correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.Item The Circulating Concentration and 24-h Urine Excretion of Magnesium Dose- and Time-Dependently Respond to Oral Magnesium Supplementation in a Meta-Analysis of Randomized Controlled Trials(Oxford, 2016-03) Zhang, Xi; Del Gobbo, Liana C.; Hruby, Adela; Rosanoff, Andrea; He, Ka; Dai, Qi; Costello, Rebecca B.; Zhang, Wen; Song, Yiqing; Epidemiology, School of Public HealthBackground: Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification. Objective: We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs). Methods: We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation. Results: Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity ≤ 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses. Conclusions: This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.Item Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo(Taylor & Francis, 2019-02) Fu, Yuanyuan; Hong, Liang; Xu, Jiecheng; Zhong, Guoping; Gu, Qiong; Gu, Qianqian; Guan, Yanping; Zheng, Xueping; Dai, Qi; Luo, Xia; Liu, Cui; Huang, Zhiying; Yin, Xiao-Ming; Liu, Peiqing; Li, Min; Pathology and Laboratory Medicine, School of MedicineHuman Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated in silico screening and in vitro assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.Item Intakes of magnesium, calcium and risk of fatty liver disease and prediabetes(Cambridge, 2018-08) Li, Wenshuai; Zhu, Xiangzhu; Song, Yiqing; Fan, Lei; Wu, Lijun; Kabagambe, Edmond; Hou, Lifang; Shrubsole, Martha; Liu, Jie; Dai, Qi; Epidemiology, School of Public HealthObjective Obesity and insulin resistance play important roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Mg intake is linked to a reduced risk of metabolic syndrome and insulin resistance; people with NAFLD or alcoholic liver disease are at high risk of Mg deficiency. The present study aimed to investigate whether Mg and Ca intakes were associated with risk of fatty liver disease and prediabetes by alcohol drinking status. Design We analysed the association between Ca or Mg intake and fatty liver disease, prediabetes or both prediabetes and fatty liver disease in cross-sectional analyses. Setting Third National Health and Nutrition Examination Survey (NHANES III) follow-up cohort of US adults. Subjects Nationally representative sample of US adults in NHANES (n 13 489). Results After adjusting for potential confounders, Mg intake was associated with approximately 30 % reduced odds of fatty liver disease and prediabetes, comparing the highest intake quartile v. the lowest. Mg intake may only be related to reduced odds of fatty liver disease and prediabetes in those whose Ca intake is less than 1200 mg/d. Mg intake may also only be associated with reduced odds of fatty liver disease among alcohol drinkers. Conclusions The study suggests that high intake of Mg may be associated with reduced risks of fatty liver disease and prediabetes. Further large studies, particularly prospective cohort studies, are warranted to confirm the findings.Item Magnesium intake and mortality due to liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort(Nature Publishing group, 2017-12-20) Wu, Lijun; Zhu, Xiangzhu; Fan, Lei; Kabagambe, Edmond K.; Song, Yiqing; Tao, Menghua; Zhong, Xiaosong; Hou, Lifang; Shrubsole, Martha J.; Liu, Jie; Dai, Qi; Epidemiology, School of Public HealthPeople with fatty liver disease are at high risk of magnesium deficiency. Meanwhile, low magnesium status is linked to both chronic inflammation and insulin resistance. However, no study has investigated the association between intake of magnesium and risk of mortality due to liver diseases. We evaluated the association between total magnesium intake and mortality due to liver diseases in the Third National Health and Nutrition Examination Study (NHANES III) cohort, which included 13,504 participants who completed liver ultrasound examination for hepatic steatosis. Overall magnesium intake was associated with a reduced risk of mortality due to liver disease at borderline significance (P = 0.05). In fully-adjusted analyses, every 100 mg increase in intake of magnesium was associated with a 49% reduction in the risk for mortality due to liver diseases. Although interactions between magnesium intake and alcohol use and hepatic steatosis at baseline were not significant (P > 0.05), inverse associations between magnesium intake and liver disease mortality were stronger among alcohol drinkers and those with hepatic steatosis. Our findings suggest higher intakes of magnesium may be associated with a reduced risk of mortality due to liver disease particularly among alcohol drinkers and those with hepatic steatosis. Further studies are warranted to confirm the findings.Item Niclosamide Triggers Non-Canonical LC3 Lipidation(MDPI, 2019-03-15) Liu, Yajun; Luo, Xia; Shan, Hao; Fu, Yuanyuan; Gu, Qianqian; Zheng, Xueping; Dai, Qi; Xia, Fan; Zheng, Zhihua; Liu, Peiqing; Yin, Xiao-Ming; Hong, Liang; Li, Min; Pathology and Laboratory Medicine, School of MedicineAutophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this study, we found that Nic could also induce NCLL, which is independent of the ULK1 complex and Beclin 1 complex, but dependent on ubiquitin-like conjugation systems. Although bafilomycin A1 and concanamycin A, two known V-ATPase inhibitors, significantly inhibited Nic-induced NCLL, Nic-induced NCLL was demonstrated to be independent of V-ATPase. In addition, the Golgi complex and vimentin were involved in Nic-induced NCLL, which might be a platform or membrane source for Nic-induced LC3-positive structures. These results would be helpful to broaden our understanding of the working mechanisms of Nic and evaluate its pharmacological activities in diseases.Item Serum Magnesium Concentrations and All-cause, Cardiovascular, and Cancer Mortality among U.S. Adults: Results from The NHANES I Epidemiologic Follow-up Study(Elsevier, 2017) Zhang, Xi; Xia, Jin; Del Gobbo, Liana C.; Hruby, Adela; Dai, Qi; Song, Yiqing; Epidemiology, School of Public HealthBackground Few studies have examined the associations of serum magnesium (Mg) concentrations with total and cause-specific mortality in a nationally representative sample of US adults. We investigate the dose–response relationships of baseline serum Mg concentrations with risk of mortalities in a large, nationally representative sample of US adults. Methods We analyzed prospective data of 14,353 participants aged 25–74 years with measures of serum Mg concentrations at baseline (1971–1975) from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS). Mortality data was linked through December 31, 2011. We estimated the mortality hazard ratios (HRs), for participants within serum Mg categories of <0.7, 0.7–0.74, 0.75–0.79, 0.8–0.89 (referent), 0.9–0.94, 0.95–0.99, and ≥1.0 mmol/L using weighted multivariate-adjusted Cox proportional hazards models. Results During a median follow-up of 28.6 years, 9012 deaths occurred, including 3959 CVD deaths, 1923 cancer deaths, and 708 stroke deaths. The multivariate-adjusted HRs (95% CIs) of all-cause mortality across increasing categories of Mg were 1.34 (1.02, 1.77), 0.94 (0.75, 1.18), 1.08 (0.97, 1.19), 1.00 (referent), 1.05 (0.95, 1.16), 0.96 (0.79, 1.15), and 0.98 (0.76, 1.26). Similar trends were observed for cancer (HRs for serum Mg < 0.7: 1.39, 95% CI: 0.83, 2.32) and CVD mortality (HRs for serum Mg < 0.7: 1.28, 95% CI: 0.81, 2.02) but were not statistically significant. An elevated risk for stroke mortality was observed among participants with serum Mg < 0.70 mmol/L (HR: 2.55, 95% CI: 1.18, 5.48). Conclusions Very low serum Mg concentrations were significantly associated with an increased risk of all-cause mortality in US adults.Item SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials(Springer, 2017-10) Tang, Huilin; Dai, Qi; Shi, Weilong; Zhai, Suodi; Song, Yiqing; Han, Jiali; Epidemiology, School of Public HealthAims/hypothesis The association between sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. Methods We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. Results In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). Conclusions/interpretation Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.Item SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials(Springer, 2017-09) Tang, Huilin; Dai, Qi; Shi, Weilong; Zhai, Suodi; Song, Yiqing; Han, Jiali; Epidemiology, School of Public HealthAims/hypothesis The association between sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. Methods We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. Results In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). Conclusions/interpretation Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.