The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis DOI Creative Commons
Xianlei Cai, Xueying Li, Chao Liang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 24, 2024

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has highest incidence malignant tumors system. We performed two-sample Mendelian randomization analysis to explore associations between 19 metabolism-related lifestyle clinical risk DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, pancreatic cancer. The causal association was explored for all combinations each factor DSC. gathered information on instrumental variables (IVs) from various sources retrieved outcome Biobank Japan (BBJ). data were studies east Asian populations. Finally, 17,572 DSCs cases 195,745 controls included. Our found that genetically predicted alcohol drinking strong indicator gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) hepatocellular carcinoma (OR 1.11; CI: 1.05-1.18), whereas coffee consumption had potential protective effect 0.69; 0.53-0.90). Triglyceride potentially associated with decreased tract 0.53; 0.34-0.81), uric acid 0.59; 0.37-0.96). syndrome (MetS) esophageal Additionally, there no evidence other factors, body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total glycine, creatinine, gout, Graves' disease, DSCs. leave-one-out revealed single nucleotide polymorphism (SNP) rs671 ALDH2 gene disproportionately high contribution carcinoma, as well carcinoma. present study multiple valuable SNP highlighting significance metabolic both prevention treatment

Language: Английский

Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease DOI Creative Commons
Ziang Li, Bin Zhang, Qing‐Rong Liu

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 90, P. 104543 - 104543

Published: March 30, 2023

Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether causative NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in evaluate potential effect drug targets on NAFLD.Genetic variants associated with genes encoding were extracted from Global Lipids Genetics Consortium genome-wide association (GWAS). Summary statistics obtained two independent GWAS datasets. Lipid-lowering reached significance further tested using expression quantitative trait loci data relevant tissues. Colocalisation mediation analyses performed validate robustness results mediators.No significant eight was found. Genetic mimicry lipoprotein lipase (LPL) enhancement risks datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 2.07 × 10-8; OR2 0.57 0.39-0.82], p2 3.00 10-3). A MR (OR 0.71 CI, 0.58-0.87], p 1.20 10-3) strong colocalisation (PP.H4 0.85) observed LPL subcutaneous adipose tissue. Fasting insulin type 2 diabetes mediated 7.40% 9.15%, respectively, total risk.Our findings do not support as Among nine targets, promising candidate target The mechanism action be its effects.Capital's Funds Health Improvement Research (2022-4-4037). CAMS Innovation Fund Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Language: Английский

Citations

83
Insights into modifiable risk factors of erectile dysfunction, a wide-angled Mendelian Randomization study DOI Creative Commons
Yang Xiong, Fuxun Zhang, Yangchang Zhang

et al.

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 58, P. 149 - 161

Published: May 25, 2023

The causal association between modifiable risk factors and erectile dysfunction (ED) remains unclear, which hinders the early identification intervention of patients with ED. present study aimed to clarify 42 predominant

Language: Английский

Citations

46
Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction DOI Creative Commons
Karli R. LeFort, Wiramon Rungratanawanich, Byoung‐Joon Song

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Abstract This review provides an update on recent findings from basic, translational, and clinical studies the molecular mechanisms of mitochondrial dysfunction apoptosis hepatocytes in multiple liver diseases, including but not limited to alcohol-associated disease (ALD), metabolic dysfunction-associated steatotic (MASLD), drug-induced injury (DILI). While ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via microsomal ethanol system, it also metabolizing many xenobiotics, pollutants, chemicals, drugs, specific diets abundant n-6 fatty acids, into toxic metabolites organs, liver, causing pathological insults through organelles such as mitochondria endoplasmic reticula. Oxidative imbalances (oxidative stress) promote covalent modifications lipids, proteins, nucleic acids enzymatic non-enzymatic mechanisms. Excessive changes stimulate various post-translational (PTMs) transcription factors, histones. Increased PTMs proteins inactivate enzymes involved reduction oxidative species, acid metabolism, mitophagy pathways, leading dysfunction, energy depletion, apoptosis. Unique other organelles, control signaling cascades bioenergetics (fat metabolism), inflammation, apoptosis/necrosis hepatocytes. When homeostasis shifted, these pathways become altered or shut down, likely contributing death with activation inflammation hepatic stellate cells, fibrosis cirrhosis. will encapsulate how contributes hepatocyte several types diseases order provide recommendations targeted therapeutics.

Language: Английский

Citations

36
Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases DOI Creative Commons

Reddemma Sandireddy,

Suganya Sakthivel,

Priyanka Gupta

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 16, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty (NAFLD), is the most common disorder worldwide, with an estimated global prevalence of more than 31%. steatohepatitis (MASH), formerly (NASH), a progressive form MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide comprehensive analysis extrahepatic manifestations MASH, focusing on chronic diseases related cardiovascular, muscular, renal systems. A systematic published studies literature was conducted summarize findings systemic impacts MASH. The focused association MASH metabolic comorbidities, cardiovascular mortality, sarcopenia, kidney disease. Mechanistic insights into concept lipotoxic inflammatory "spill over" from MASH-affected were also explored. are highly associated (50%-80%) other comorbidities such impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, hypertension. Furthermore, 90% obese patients diabetes have Data suggest that in middle-aged individuals (especially those aged 45-54), independent risk factor for plays crucial role mediating pathological effects observed. Understanding multifaceted impact heart, muscle, early detection stratification. knowledge timely implementing management strategies addressing multi-organ involvement pathogenesis.

Language: Английский

Citations

26
The impact of obesity: a narrative review DOI Creative Commons

Benjamin Chih Chiang Lam,

Amanda Yuan Ling Lim,

Soo Ling Chan

et al.

Singapore Medical Journal, Journal Year: 2023, Volume and Issue: 64(3), P. 163 - 171

Published: Feb. 28, 2023

Obesity is a disease with major negative impact on human health. However, people obesity may not perceive their weight to be significant problem and less than half of patients are advised by physicians lose weight. The purpose this review highlight the importance managing overweight discussing adverse consequences obesity. In summary, strongly related >50 medical conditions, many them having evidence from Mendelian randomisation studies support causality. clinical, social economic burdens considerable, these potentially impacting future generations as well. This highlights health an urgent concerted effort towards prevention management reduce burden

Language: Английский

Citations

39
Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study DOI Creative Commons
Hui Gao,

Shuhao Zheng,

Xin Yuan

et al.

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 10, 2023

The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it not clear whether there a causal relationship. We aimed to systematically estimate the relationship between IBD and cancers.Independent genetic variants strongly associated with were extracted as instrumental variables from genome-wide association study (GWAS) conducted by International Genetics Consortium including 12,882 5956 Crohn's (CD) 6968 ulcerative colitis (UC) patients. Three sources GWAS selected outcome data. Two-sample Mendelian randomization (MR) analysis was assess effects on 32 cancers. meta-analysis applied combined effect multiple MR results.IBD, CD, UC have potential associations oral cavity (IBD: OR = 1.180, 95% CI: 1.059 1.316, P 0.003; CD: 1.112, 1.008 1.227, 0.034; UC: 1.158, 1.041 1.288, 0.007). Meta-analysis showed significant positive breast (OR 1.059; 1.033 1.086; < 0.0001) well CD 1.029; 1.002 1.055; 0.032) based combining results.This comprehensive suggested that genetically predicted IBD, its subtypes, may be factor development cancer.

Language: Английский

Citations

26
Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study DOI Creative Commons
Lilong Zhang,

Liuliu Zi,

Tianrui Kuang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 5, 2023

Objective There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic (ALD), viral hepatitis, but no studies have explored their causal relationship. Methods Instrumental variables of the (N = 13266) microbiota-derived metabolites 7824) were acquired, a Mendelian randomization study was performed to explore influence on NAFLD (1483 European cases 17,781 controls), ALD (2513 332,951 hepatitis risk (1971 340,528 controls). The main method examining causality inverse variance weighting (IVW). Results IVW results confirmed that Anaerotruncus ( p 0.0249), Intestinimonas 0.0237), Lachnoclostridium 0.0245), Lachnospiraceae NC2004 group 0.0083), Olsenella 0.0163), Peptococcus 0.0472) protective factors NAFLD, Ruminococcus 1 0.0120) detrimental NAFLD. higher abundance three genera, Lachnospira 0.0388), Desulfovibrio 0.0252), torques 0.0364), correlated with lower ALD, while Ruminococcaceae UCG 002 level associated 0.0371). Alistipes 0.0069) NK4A214 0.0195) related hepatitis. Besides, alanine 0.0076) phenyllactate 0.0100) found be negatively stachydrine (O 0.0244) positively phenylacetate 0.0353) ursodeoxycholate 0.0144) had effect threonate 0.0370) exerted ALD. estimates 0.0408) cholate 0.0293) showed suggestive harmful effects against 0.0401) displayed its Conclusion In conclusion, our research supported links microbiome

Language: Английский

Citations

24
NAFLD: An Emerging Causal Factor for Cardiovascular Disease DOI
Mei Li, Horng‐Dar Wang, Xiao‐Jing Zhang

et al.

Physiology, Journal Year: 2023, Volume and Issue: 38(6), P. 255 - 265

Published: July 11, 2023

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic worldwide that poses a significant threat to human health. Cardiovascular (CVD) leading cause of mortality in NAFLD patients. and CVD share risk factors such as obesity, insulin resistance, type 2 diabetes. However, whether causal factor for remains matter debate. This review summarizes evidence from prospective clinical Mendelian randomization studies underscore potential relationship between CVD. The mechanisms contributing development necessity addressing while managing practice are also discussed.

Language: Английский

Citations

24
Thyroid hormone receptor-β analogs for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) DOI Creative Commons
Vlad Ratziu, Thomas S. Scanlan, Eveline Bruinstroop

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

11
Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study DOI
Shanshan Ran, Jingyi Zhang, Fei Tian

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

9