Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

Liu, Peng; Li, Ming; Wu, Wei; Liu, Anjie; Hu, Honglin; Liu, Qin; Yi, Chengzhi

doi:10.1080/13880209.2023.2168018

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…The mammalian target of rapamycin (mTOR), a class of serine/threonine kinases, is an intracellular signaling molecule 244 . Abnormal activation of mTOR signaling can lead to multiple adverse outcomes, including tumor formation, neonatal insulin resistance, and adipogenesis 245 . Inactivating mutations in TSC2 cause hamartomas primarily in multiple organ systems 246 .…”

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

“… 244 Abnormal activation of mTOR signaling can lead to multiple adverse outcomes, including tumor formation, neonatal insulin resistance, and adipogenesis. 245 Inactivating mutations in TSC2 cause hamartomas primarily in multiple organ systems. 246 Loss of TSC2 enhances the sensitivity of hepatoma cell lines to everolimus and AZD8055.…”

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

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Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

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Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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“…Polyunsaturated fatty acids (PUFAs) are essential nutrients that play a crucial role in the development and progression of several infectious diseases. Among them, a heightened level of omega-3 fatty acids and docosahexaenoic acid (DHA) have been demonstrated to be associated with improved sepsis outcomes in both experimental and observational studies [4][5][6][7][8][9]. However, traditional observational studies could not entirely exclude confounding biases or reverse causality.…”

Section: Introductionmentioning

confidence: 99%

Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk

Lei

Wang

et al. 2023

Infect Dis Ther

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Introduction Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. Methods We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane’s Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. Results The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845–0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815–0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681–0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011–1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. Conclusion Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00831-z.

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Ziqi Dihuang decoction ameliorates thrombosis in septic rats by inhitbiting plasminogen activator inhibitor-1

Geng

Fei

Pei

et al. 2023

Journal of Traditional and Complementary Medicine

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Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

Cited by 3 publications

References 43 publications

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk

Ziqi Dihuang decoction ameliorates thrombosis in septic rats by inhitbiting plasminogen activator inhibitor-1

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