scholarly journals Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N-oxide-generating pathway, modulates platelet responsiveness and thrombosis risk

2018 ◽  
Vol 16 (9) ◽  
pp. 1857-1872 ◽  
Author(s):  
W. Zhu ◽  
J. A. Buffa ◽  
Z. Wang ◽  
M. Warrier ◽  
R. Schugar ◽  
...  
2019 ◽  
Vol 20 (9) ◽  
pp. 765-770 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Belal Azab ◽  
Al M. Best ◽  
Yousef S. Khader ◽  
...  

Background: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Variation in the activity of polymorphic CYP2A6 alleles has been implicated in inter-individual differences in nicotine metabolism. Aims: The objective of the current study was to assess the association between the smoking status and the cytochrome P450 2A6 enzyme (CYP2A6) genotype in Jordanians. Methods: In the current study, 218 (117 Male and 101 female) healthy unrelated Jordanian volunteers were recruited. CYP2A6*1B, CYP2A6*4 and CYP2A6*9 were determined and correlated with subject smoking status. Results: *1A/*1A was the most common genetic polymorphism in the overall study population, with no significant frequency differences between smokers and non-smokers. When the population was divided according to gender, only male smokers showed a significant correlation between genotype and smoking status. Considering the CYP2A6*9 genotype, the results showed differences in distribution between smokers and non-smokers, but only women showed a significant association between CYP2A6*9 allele genotype and smoking status. Conclusion: The results of this study show that there is a significant association between CYP2A6*9 genotype and smoking status. They also show that CYP2A6 genotype is significantly influenced by gender.


2021 ◽  
pp. bmjnph-2020-000183
Author(s):  
Yixuan Fang ◽  
Yue Gu ◽  
Chen Zhao ◽  
Yaqi Lv ◽  
Jiawei Qian ◽  
...  

Beego is a traditional Chinese complete water-only fasting practice initially developed for spiritual purposes, later extending to physical fitness purposes. Beego notably includes a psychological induction component that includes meditation and abdominal breathing, light body exercise and ends with a specific gradual refeeding program before returning to a normal diet. Beego has regained its popularity in recent decades in China as a strategy for helping people in subhealthy conditions or with metabolic syndrome, but we are unaware of any studies examining the biological effects of this practice. To address this, we here performed a longitudinal study of beego comprising fasting (7 and 14 day cohorts) and a 7-day programmed refeeding phase. In addition to detecting improvements in cardiovascular physiology and selective reduction of blood pressure in hypertensive subjects, we observed that beego decreased blood triacylglycerol (TG) selectively in TG-high subjects and increased cholesterol in all subjects during fasting; however, the cholesterol levels were normalised after completion of the refeeding program. Strikingly, beego reduced platelet formation, activation, aggregation and degranulation, resulting in an alleviated thrombosis risk, yet maintained haemostasis by sustaining levels of coagulation factors and other haemostatic proteins. Mechanistically, we speculate that downregulation of G6B and MYL9 may influence the observed beego-mediated reduction in platelets. Fundamentally, our study supports that supervised beego reduces thrombosis risk without compromising haemostasis capacity. Moreover, our results support that beego under medical supervision can be implemented as non-invasive intervention for reducing thrombosis risk, and suggest several lines of intriguing inquiry for future studies about this fasting practice (http://www.chictr.org.cn/index.aspx, number, ChiCTR1900027451).


2021 ◽  
Vol 10 (5) ◽  
pp. 1144
Author(s):  
Shira Azulai ◽  
Ronit Grinbaum ◽  
Nahum Beglaibter ◽  
Shai Meron Eldar ◽  
Moshe Rubin ◽  
...  

Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) on the levels of ALT by analysis of two-year follow-up data from 4980 patients in the Israeli Bariatric Registry that included laboratory tests and demographic information. Pre-operative characteristics of patients, and particularly levels of liver enzymes, were similar across surgery types. Regression modeling and retrospective matching showed that SG was superior to RYGB and OAGB in reducing ALT levels, and in reducing the fraction of patients with abnormally high ALT levels. Two-year post-surgery, an increase in ALT levels from normal to abnormal levels was observed in 5% of SG patients, and in 18% and 23% of RYGB and OAGB patients. In conclusion, SG leads to a greater reduction in ALT levels compared with bypass surgeries and a lower incidence of post-surgical elevation of ALT levels. Further studies are required to identify the cause for the rise in liver enzymes, and to determine whether ALT levels correlate with liver pathology especially following bariatric surgery.


Author(s):  
Armando Tripodi ◽  
Luisa Spina ◽  
Laura Francesca Pisani ◽  
Lidia Padovan ◽  
Flaminia Cavallaro ◽  
...  

Abstract Background Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation. Methods Forty patients with IBD were compared with 57 control patients for coagulation factors and endogenous thrombin potential (ETP), the latter being the most sensitive marker of in vivo pro- and anticoagulation balance. We measured ETP in the presence and absence of thrombomodulin (the physiologic protein C [PC] activator). Coagulation at different timepoints was also assessed for 28 of these patients during infliximab treatment. Results The median ETP (nM thrombin × minutes) and range (minimum-maximum) were each higher in patients at baseline than in control patients in both the absence (2120 [1611-3041] vs 1865 [1270-2337]) and the presence (1453 [464-2522] vs 831 [104-1741]) of thrombomodulin. The ETP ratio (with/without thrombomodulin) was high at baseline (0.73 [0.21-0.90] vs 0.45 [0.07-0.85]). The ETP and ETP ratio declined during treatment and were significantly lower at the end than at baseline. Factor (F) VIII and fibrinogen, which were high at baseline, decreased during treatment and at the end were significantly lower than at baseline. The FVIII/PC ratio, which was high in patients at baseline, declined during treatment and at the end was lower than at baseline. C-reactive protein recorded at the end of treatment was lower than at baseline. Conclusions Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.


2021 ◽  
pp. 1-6
Author(s):  
Merve Sari ◽  
Yusuf Ilhan ◽  
Sema Sezgin Goksu ◽  
Osman Kostek ◽  
Ali Murat Tatli ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 228
Author(s):  
Pierre Haen ◽  
Lydie Crescence ◽  
Diane Mege ◽  
Alexandre Altié ◽  
Christophe Dubois ◽  
...  

Venous thrombo-embolism (VTE) disease is the second most common cause of mortality in cancer patients, and evaluation and prevention of thrombosis risk is essential. VTE-associated risk varies according to the type of tumor disease. Oral cancer is the most frequent type of head and neck cancer, and it represents approximately 2.1% of all cancers worldwide. Most tumors are squamous cell carcinomas and are mainly due to tobacco and alcohol abuse. VTE risk associated with oral squamous cell carcinoma (OSCC) is low. However, many studies have shown that OSCC has the following biological features of cancers associated with a high thrombosis risk: modified thrombosis and fibrinolysis mechanisms; strong expression of procoagulant proteins; secretion of procoagulant microparticles; and production of procoagulant cytokines. Using an original mouse model of tongue squamous cell carcinoma, our study aimed to clarify this paradoxical situation. First, we showed that OSCC tumors have a pro-aggregatory phenotype and a high local thrombosis risk. Second, we found that tongue tumor mice do not have an elevated systemic thrombosis risk (the risk of an “at distance” thrombosis event such as lower extremity deep venous thrombosis or pulmonary embolism) and even show a reduction in risk. Third, we demonstrated that tongue tumor mice show a reduction in platelet reactivity, which explains the low systemic thrombosis risk. Finally, we found that tongue tumor mice present granule pool deficiency, thereby explaining the reduction in platelet reactivity and systemic thrombosis risk.


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