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| 2. |
- Chen, Hongxia, et al.
(author)
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PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
- 2024
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In: Molecular Cancer Research. - 1541-7786. ; 22:1, s. 94-103
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Journal article (peer-reviewed)abstract
- Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.
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| 3. |
- Gu, Yeqing, et al.
(author)
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Consumption of ultraprocessed food and development of chronic kidney disease : the Tianjin Chronic Low-Grade Systemic Inflammation and Health and UK Biobank Cohort Studies
- 2023
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In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 117:2, s. 373-382
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Journal article (peer-reviewed)abstract
- BackgroundMany ultraprocessed food (UPF)-derived by-products may play a role in the development of chronic kidney disease (CKD). Although several studies have assessed the association of UPFs with kidney function decline or CKD in various countries, no evidence has been shown in China and the United Kingdom.ObjectivesThis study aims to evaluate the association between UPF consumption and risk of CKD in 2 large cohort studies from China and the United Kingdom.MethodsIn total, 23,775 and 102,332 participants without baseline CKD were enrolled in the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) and UK Biobank cohort studies, respectively. Information on UPF consumption was obtained from a validated food frequency questionnaire in the TCLSIH and 24-h dietary recalls in the UK Biobank cohort. CKD was defined as an estimated glomerular filtration rate of ResultsAfter a median follow-up of 4.0 and 10.1 y, the incidence rates of CKD were around 1.1% and 1.7% in the TCLSIH and UK Biobank cohorts, respectively. The multivariable hazard ratio [95% confidence interval] of CKD across increasing quartiles (quartiles 1–4) of UPF consumption were 1 (reference), 1.24 (0.89, 1.72), 1.30 (0.91, 1.87), and 1.58 (1.07, 2.34) (P for trend = 0.02) in the TCLSIH cohort and 1 (reference), 1.14 (1.00, 1.31), 1.16 (1.01, 1.33), and 1.25 (1.09, 1.43) (P for trend < 0.01) in the UK Biobank cohort, respectively.ConclusionsOur finding indicated that higher UPF consumption is associated with a higher risk of CKD. Moreover, restricting UPF consumption may potentially benefit the prevention of CKD. Further clinical trials are required to clarify the causality.
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| 4. |
- Huang, Huiping, 1991, et al.
(author)
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Low-Rank and Row-Sparse Decomposition for Joint DOA Estimation and Distorted Sensor Detection
- 2023
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In: IEEE Transactions on Aerospace and Electronic Systems. - 1557-9603 .- 0018-9251. ; 59:4, s. 4763-4773
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Journal article (peer-reviewed)abstract
- Distorted sensors could occur randomly and may lead to the breakdown of a sensor array system. In this article, we consider an array model within which a small number of sensors are distorted by unknown sensor gain and phase errors. With such an array model, the problem of joint direction-of-arrival (DOA) estimation and distorted sensor detection is formulated under the framework of low-rank and row-sparse decomposition. We derive an iteratively reweighted least squares (IRLS) algorithm to solve the resulting problem. The convergence property of the IRLS algorithm is analyzed by means of the monotonicity and boundedness of the objective function. Extensive simulations are conducted regarding parameter selection, convergence speed, computational complexity, and performances of DOA estimation as well as distorted sensor detection. Even though the IRLS algorithm is slightly worse than the alternating direction method of multipliers in detecting the distorted sensors, the results show that our approach outperforms several state-of-the-art techniques in terms of convergence speed, computational cost, and DOA estimation performance.
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| 5. |
- Liu, Li, et al.
(author)
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Cardiomyocyte-specific Loss of Diacylglycerol Acyltransferase 1 (DGAT1) Reproduces the Abnormalities in Lipids Found in Severe Heart Failure
- 2014
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:43, s. 29881-29891
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Journal article (peer-reviewed)abstract
- Background: Total body DGAT1 mice have no cardiac phenotype. Results: Cardiomyocyte DGAT1 knock-out mice have increased mortality and accumulation of potentially toxic lipids, which were corrected by intestinal DGAT1 deletion and GLP-1 receptor agonists. Conclusion: Cardiomyocyte DGAT1 deletion produces heart dysfunction and lipid abnormalities. Significance: Lipotoxicity in the heart can be alleviated by changes in intestinal metabolism. Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase C (PKC), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
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| 6. |
- Ma, Yue, et al.
(author)
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Acid suppressants use and risk of atherosclerotic cardiovascular disease in middle-aged and older adults
- 2022
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 358, s. 47-54
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Journal article (peer-reviewed)abstract
- Background and aims: Concerns regarding adverse events associated with the use of acid suppressants have increased. However, the impact of proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) on the risk of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to estimate the risk of ASCVD in association with the use of PPIs and H2RAs. Methods: This prospective cohort study included participants without cardiovascular diseases or anti-hypertensive treatment at baseline (2006–2010) in the UK Biobank. The outcomes were ASCVD and each subtype (coronary artery disease, myocardial infarction, peripheral artery disease, and ischemic stroke). The association was estimated by Cox proportional-hazards models. Results: Among 316,730 individuals (aged 50–88 years), during a median of 12.5 years of follow-up, we documented 13,503 (4.3%) incident ASCVD. Regular PPIs use was associated with a higher risk of ASCVD (HR: 1.16, 95% CI: 1.09–1.23) and every subtype of ASCVD. Among each type of PPIs, omeprazole (HR: 1.19, 95% CI: 1.11–1.28), lansoprazole (HR: 1.11, 95% CI: 1.02–1.22), and pantoprazole (HR: 1.40, 95% CI: 1.00–1.97) were associated with a higher risk of ASCVD. Stratification analysis showed that PPIs use was associated with a higher risk of ASCVD among individuals without indications of medications for PPIs. In addition, use of H2RAs was not related to the risk of ASCVD (HR: 0.97, 95% CI: 0.85–1.11). Conclusions: PPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs.
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| 7. |
- Yang, Anning, et al.
(author)
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Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation
- 2023
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In: Acta Biochimica et Biophysica Sinica. - : China Science Publishing & Media Ltd.. - 1672-9145. ; 55:8, s. 1184-1192
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Journal article (peer-reviewed)abstract
- Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High level of homocysteine (Hcy) promotes autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). The results show that Hcy-induced autophagy level is mediated by upregulation of TFEB. Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.
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| 8. |
- Zhang, Shunming, et al.
(author)
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Added sugar intake and its forms and sources in relation to risk of non-alcoholic fatty liver disease : results from the Tianjin Chronic Low-grade Systemic Inflammation and Health cohort study
- 2023
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In: British Journal of Nutrition. - 1475-2662. ; 129:12, s. 2094-2101
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Journal article (peer-reviewed)abstract
- It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid vs. solid), and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15,538 participants, free of NAFLD, other liver diseases, cardiovascular disease, cancer, or diabetes at baseline (2013-2018 years). Added sugar intake was estimated from a validated 100-item food frequency questionnaire. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for NAFLD risk with added sugar intake. During a median follow-up of 4.2 years, 3,476 incident NAFLD cases were documented. After adjusting for age, sex, body mass index and its change from baseline to follow-up, lifestyle factors, personal and family medical history, and overall diet quality, the multivariable HRs (95% CIs) of NAFLD risk were 1.18 (1.06, 1.32) for total added sugars, 1.20 (1.08, 1.33) for liquid added sugars, and 0.96 (0.86, 1.07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
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