Good or bad: Paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors

Wang, Bofang; Gu, Baohong; Zhang, Tao; Li, Xuemei; Wang, Na; Ma, Chenhui; Lin, Xin; Wang, Yunpeng; Gao, Lei; Yu, Yang; Song, Kun; He, Puyi; Wang, Yueyan; Zhu, Jie; Chen, Hao

doi:10.1016/j.canlet.2023.216117

Cited by 7 publications

(2 citation statements)

References 123 publications

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“…It plays an essential role in various physiological processes, including coagulation, brinolysis, vasodilation, in ammation, and regulation of vascular permeability [42]. PAI-1, an acute phase response protein and a signi cant inhibitor in the brinolytic system, is upregulated in cardiovascular diseases, metabolic syndrome, venous thrombosis, cancer, and in ammation [43][44][45][46]. In sepsis patients, elevated PAI-1 levels are positively correlated with disease severity and mortality [47].…”

Section: Discussionmentioning

confidence: 99%

No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study

Lei,

Qi,

Zhai

et al. 2024

Preprint

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Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Among the critical hallmarks of sepsis progression is the abnormal activation of coagulation, particularly the onset of disseminated intravascular coagulation, which often indicates a higher risk of mortality. However, due to the complexity of the coagulation system and the lack of prospective sepsis cohorts, understanding the relationship between coagulation factors and sepsis-related risk remains limited. Therefore, this study aims to investigate the association between coagulation factor levels and related protein expressions with the risk of sepsis incidence, ICU admission, and 28-day mortality using publicly available GWAS summary statistics through MR analysis. Methods To explore the causal relationship between coagulation factors and sepsis-related risks, we employed a two-sample MR analysis framework. After rigorous quality control, we extracted 99 SNPs influencing the plasma levels of 16 coagulation factors from GWAS. Cis-eQTLs regulating sepsis-related coagulation genes were extracted from the eQTLgen database as instrumental variables. We then utilized sepsis GWAS data from independent European ancestry cohorts: UK Biobank and FinnGen as outcome data for MR analysis. We calculated MR estimates using various methods and conducted sensitivity analyses to ensure the robustness of the analysis. Results The causal effect sizes between genetically predicted levels of coagulation factors and the risk of sepsis incidence, ICU admission, and 28-day mortality did not reach statistical significance. The expression of the TMEM173 gene showed a positive effect on the risk of ICU admission for sepsis (IVW: beta = 0.362, P = 0.0264; Weighted Median: beta = 0.386, P = 0.0123). Conclusions Our MR study does not support a presumed causal effect between coagulation factor levels and the risk of sepsis incidence, ICU admission, and 28-day mortality in European populations.

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Section: Discussionmentioning

confidence: 99%

No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study

Lei,

Qi,

Zhai

et al. 2024

Preprint

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“…The presence of fibrosis was assessed by the content of biochemical markers in the liver homogenate -HP free (HPf), HP protein-bound (HPp/b) and GAG. The content of GAG was evaluated by Rimington's method, HPp/b and HPf -by Osadchuk's method [2,13].…”

Section: Methodsmentioning

confidence: 99%

Liver structure and fibrosis markers in modeling alcohol-induced liver injury and correction of detected disorders

Didenko,

Klenina,

Hrabovska

et al. 2023

GASTRO

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Background. Chronic alcohol use leads to alcoholic liver fibrosis. Today, a sufficient number of scientific studies are focused on the pathometabolic mechanisms of liver fibrosis development and formation in animal models. The purpose of our study was to investigate structural changes and liver stiffness, biochemical markers of fibrosis in rats with chronic alcoholic liver injury (CALI) modeling and to evaluate the changes of these parameters with different types of treatment. Materials and methods. Eighty-nine rats were divided into experimental groups depending on the duration of alcohol exposure (4 and 12 weeks) and the corresponding type of correction (metadoxine and prebiotic). Results. When modeling CALI at week 4, morphological studies revealed moderate large-droplet fatty hepatosis and mild fibrosis in the central venule of the liver lobes. After 12 weeks of forced alcoholization, with more pronounced general intoxication, hepatocytes have dystrophic changes such as appearance of single or grouped dystrophic cells in the parenchyma. A combination of protein and fatty dystrophy was more common. Elastography allowed to detect structural changes in the liver at the early stages of fibrosis formation when modeling CALI for 12 weeks. There were also changes in the levels of biochemical parameters: free and protein-bound hydroxyproline, glycosaminoglycans. According to the results of elastography, liver stiffness in rats increased maximally after prebiotic correction in all approaches compared to the controls. After correction of CALI, both early- and long-term, fibrosis markers normalized in rat liver homogenate after administration of metadoxine and prebiotic. After prebiotic correction at week 12 of alcoholization, we observed a 12% decrease in liver parenchymal stiffness in the CALI modeling group and a 19% decrease (p < 0.05) in the placebo group. After correction with metadoxine, there was a 1.5-fold increase in free hydroxyproline levels in rat liver homogenate at week 12 and a 1.2-fold increase in glycosaminoglycans (p < 0.05) at week 4 compared to the CALI modeling group. Conclusions. Long-term alcoholization of animals led to the development of dystrophic changes in hepatocytes, protein and fatty degeneration, and an increase in the number of capillaries. Against this background, liver stiffness and biochemical parameters changed. After correction with metadoxine and prebiotic, changes in the liver stiffness and fibrosis markers were observed at week 12 of CALI modeling.

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PAI-1 Deficiency Promotes NET-mediated Pyroptosis and Ferroptosis during Pseudomonas Aeruginosa-induced Acute Lung Injury by Regulating the PI3K/MAPK/AKT Axis

Aji,

Wang,

Wang

et al. 2024

Inflammation

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Good or bad: Paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors

Cited by 7 publications

References 123 publications

No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study

No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study

Liver structure and fibrosis markers in modeling alcohol-induced liver injury and correction of detected disorders

PAI-1 Deficiency Promotes NET-mediated Pyroptosis and Ferroptosis during Pseudomonas Aeruginosa-induced Acute Lung Injury by Regulating the PI3K/MAPK/AKT Axis

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