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The remodeling pathway of PAF and lyso-PAF biosynthesis. PAF-AH converts active PAF to the inactive lyso-PAF by the loss of an acetate group at the sn-2 position. Lyso-PAF AT converts lyso-PAF back to the active PAF by the reincorporation of an acetate back to the sn-2 position. Acetyl-CoA, acetyl coenzyme A; AT, acetyltransferase; Lyso-PAF, lyso-platelet-activating factor; PAF, platelet-activating factor; PAF-AH, platelet-activating factor acetylhydrolase.
Source publication
Cancer is the second leading cause of mortality worldwide. The role of unresolved inflammation in cancer progression and metastasis is well established. Platelet-activating factor (PAF) is a key proinflammatory mediator in the initiation and progression of cancer. Evidence suggests that PAF is integral to suppression of the immune system and promot...
Contexts in source publication
Context 1
... is hypothesized that the de novo pathway is responsible for endogenous PAF production to maintain physiological concentrations, whereas the remodeling route leads to production of PAF in response to inflammatory stimuli and is the main pathway involved in inflammatory cascades (23,48). A simplified schematic of the remodeling pathway is presented in Figure 2. Long-term induction of PAF-CPT gradually increases systemic PAF with related consequences. ...
Context 2
... is hypothesized that the de novo pathway is responsible for endogenous PAF production to maintain physiological concentrations, whereas the remodeling route leads to production of PAF in response to inflammatory stimuli and is the main pathway involved in inflammatory cascades (23,48). A simplified schematic of the remodeling pathway is presented in Figure 2. Long-term induction of PAF-CPT gradually increases systemic PAF with related consequences. ...
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Background:
Mediterranean dietary pattern has attracted great attention in terms of its effect on human health. However, whether Mediterranean dietary pattern is an independent protective factor for prostate cancer remains controversial. Our goal was to evaluate this association by conducting a meta-analysis of observational studies.
Methods:
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Background: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. Objective: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population...
Objective:
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Methods:
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Citations
... It can be hypothesized that PAF levels may affect cellular health and thus PA. Given the prognostic role of PA in diseases (47)(48)(49)(50)(51) where PAF is implicated (16,(52)(53)(54), the identification of potential modulators of PA is crucial. Thus, the aim of the present work was to study the associations of PA with PAF, its metabolic enzymes, and related dietary parameters in healthy participants. ...
Introduction
Phase angle (PA) is derived from bioelectrical impedance analysis (BIA). It reflects cell membrane function and decreases in disease. It is affected by inflammation, oxidative stress, and diet. Platelet-activating factor (PAF) is a potent inflammatory lipid mediator. Its levels, along with the activity of its metabolic enzymes, including CDP-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase, acetyl-CoA:lyso-PAF-acetyltransferases, and PAF-AH/Lp-PLA2 are also related to dietary factors, such as the dietary antioxidant capacity (DAC). The aim of the study was to estimate whether the PAF metabolic circuit and related dietary factors are associated with PA in healthy volunteers.
Methods
In healthy subjects, PAF, its metabolic enzyme activity, and erythrocyte fatty acids were measured, while desaturases were estimated. Food-frequency questionnaires and recalls were used, and food groups, macronutrient intake, MedDietScore, and DAC were assessed. Lifestyle and biochemical variables were collected. DXA and BIA measurements were performed.
Results
Lp-PLA2 activity was positively associated with PA (rho = 0.651, p < 0.001, total population; rho = 0.780, p < 0.001, women), while PAF levels were negatively associated with PA only in men (partial rho = −0.627, p = 0.012) and inversely related to DAC. Estimated desaturase 6 was inversely associated with PA (rho = −0.404, p = 0.01, total sample). Moreover, the DAC correlated positively with PA (rho = 0.513, p = 0.03, women). All correlations were adjusted for age, body mass index, and sex (if applicable).
Conclusion
PA is associated with PAF levels and Lp-PLA2 activity in a gender-dependent fashion, indicating the involvement of PAF in cell membrane impairment. The relationship of PA with DAC suggests a protective effect of antioxidants on cellular health, considering that antioxidants may inhibit PAF generation.
... Noncommunicable diseases account for most deaths worldwide. However, decades of research show that dietary and lifestyle factors play a significant role in the onset and progression of many noncommunicable diseases, including cardiovascular diseases (CVD) and cancers [2][3][4][5]. Furthermore, NCDs may be risk factors for communicable disease severity as is the case for the Coronavirus disease 2019 (COVID-19) [6,7], or indeed NCDs can increase the risk of developing other NCDs leading to individuals with many comorbidities. ...
Noncommunicable diseases (NCDs) are on the rise due to population growth and aging, which will cause a significant burden on global health systems [...]
... Many lipid signaling molecules are involved in signal transduction cascades, which in turn regulate various oncogenic processes such as cell proliferation, migration, invasion, immune response, and metastasis. Among them, phosphatidylinositol 3,4,5-trisphosphate (PIP3), lysophospholipid, prostaglandin (PG), and platelet-activating factor (PAF) play a role in tumor signal transduction plays a key role (Goncalves et al. 2018;Sipos et al. 2021;Wang et al. 2022;Lordan et al. 2019). PIP3 is an important phosphatidylinositol that regulates cell survival, proliferation, and growth and can be dephosphorylated by the phosphatase PTEN to terminate PI3K signaling. ...
... In addition, the generation of PGE2 through the action of cyclooxygenase-2 (COX-2) can promote colon cancer cell proliferation, invasion, metastasis, angiogenesis, drug resistance, inhibit colon cancer apoptosis, and target COX-2/PGE2 The/EP receptor has a good effect on colon cancer (Cai and Gao 2021), and PGE2 mainly promotes tumor progression by promoting tumor angiogenesis, inducing tumor cell proliferation, and inhibiting apoptosis (De Paz Linares et al. 2021). In addition, PAF, as a lipid signaling molecule, is a key pro-inflammatory mediator in tumorigenesis and progression (Lordan et al. 2019). PAF plays an irreplaceable role in suppressing the immune system and promoting tumor growth and metastasis by altering local angiogenesis and cytokine networks. ...
Background
Abnormal metabolism is the main hallmark of cancer, and cancer metabolism plays an important role in tumorigenesis, metastasis, and drug resistance. Therefore, studying the changes of tumor metabolic pathways is beneficial to find targets for the treatment of cancer diseases. The success of metabolism-targeted chemotherapy suggests that cancer metabolism research will provide potential new targets for the treatment of malignant tumors.
Purpose
The aim of this study was to systemically review recent research findings on targeted inhibitors of tumor metabolism. In addition, we summarized new insights into tumor metabolic reprogramming and discussed how to guide the exploration of new strategies for cancer-targeted therapy.
Conclusion
Cancer cells have shown various altered metabolic pathways, providing sufficient fuel for their survival. The combination of these pathways is considered to be a more useful method for screening multilateral pathways. Better understanding of the clinical research progress of small molecule inhibitors of potential targets of tumor metabolism will help to explore more effective cancer treatment strategies.
... Alterations to these lipids are implicated in the pathogenesis of intestinal diseases [5,185], including colorectal cancers [186][187][188][189][190]. Indeed, it has been suggested that changes to the content and composition of GLS and in particular accelerated catabolism of GLS in the intestine may be indicative of a pro-inflammatory environment and potentially prognostic of tumor development [191]. Hence, polar lipids have been touted as targets for intervention by dietary and supplementation strategies [5,192]. Dairy products in particular are a rich source of SM and other polar lipids [2]. ...
Background
Milk contains polar lipids may confer health benefits upon consumption. Therefore, polar lipids have received considerable attention for development in the nutraceutical and pharmaceutical space. We review the prophylactic and therapeutic potential of milk polar lipids and their current market trends.
Methods
The following databases were used to retrieve articles for this narrative review: SCOPUS, ScienceDirect, PubMed, and Google Scholar. The search criteria included the following keywords and synonyms combined: (“milk polar lipids” or “milk phospholipids” or “milk glycerophospholipids” or “milk sphingolipids”) AND (“anti-inflammatory” or “cardiovascular” or “cancer” or “cognitive health” or “nutraceutical” or “pharmaceutical” or “supplement”).
Results
Milk polar lipid supplementation appears to improve cognitive health in both child development and age-associated cognitive decline. Milk polar lipids modulate cardiovascular risk factors including lipid levels, inflammation, and platelet function in preclinical studies, but evidence is limited in humans. Milk polar lipids may also affect colon cancer pathogenesis through anti-inflammatory mechanisms. Polar lipids are gaining attention in the nutraceutical and pharmaceutical space for their use in the development of novel therapeutics and pharmaceutical delivery systems.
Conclusions
Milk polar lipids exhibit a multitude of health benefits that may be of value in the nutraceutical and pharmaceutical industries as reflected in current market and research trends for the use of polar lipids and the development of products targeting infant cognitive development, cognitive decline in the aged, cardiovascular diseases, and cancer. Further clinical studies are required to assess efficacy and safety of milk polar lipid supplementation in human diseases.
... To date, one of the leading causes of BC development is tobacco smoking [6]. Previous research revealed that smoking contributes to elevated platelet-activating factor (PAF) development and PAF receptor (PAF-R) manifestation, thus increasing chances of tumors and metastasis formation among smokers [1,7]. PAF has been demonstrated to play a key part in the inflammatory process, thereby affecting endothelium with inflammation. ...
Background:
Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery.
Methods:
Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials.
Results:
The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3.
Conclusion:
Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC.
... In atherosclerosis, PAF is thought to play a contributory role to all stages of atherosclerosis from initiation, and development of lesions, all the way to plaque rupture. However, it is thought that PAF antagonists such as polar lipids may act as inhibitors of the PAF pathway reducing the inflammatory milieu resulting from the engagement of polar lipids with the PAF-R (Lordan et al., 2019b(Lordan et al., , 2019c. These polar lipids are abundant in marine foods, particularly fish. ...
Cardiovascular diseases (CVD) are the leading cause of death worldwide. An unhealthy diet and lifestyle are well-known risk factors for the development of CVD, however, these factors are modifiable. Epidemiological evidence has shown that the regular consumption of fish is associated with the prevention of CVD and related diseases. However, particularly in Western societies, fish consumption is generally low. Moreover, significant waste is produced due to byproducts and bycatch associated with the fishing and aquaculture industries. Therefore, there has been a concerted effort to reduce waste while developing useful products from the leftover materials of fisheries. This includes the development of value-added fish-derived functional foods contributing to cardiovascular health maintenance and the prevention of disease. In this chapter, the development of such products from functional marine lipids and proteins is discussed. Novel green extraction technologies of bioactive compounds from fish and fishery byproducts are assessed and the factors affecting consumer acceptance of fish-derived functional foods are also discussed.
... In contrast to the water-soluble extracts of apples that showed very little to no antiplatelet effects, it was recently found that apples, apple juice, and apple cider contain several polar lipid bioactives, which have shown strong anti-inflammatory and antiplatelet functional properties Tsoupras et al. 2021aTsoupras et al. , 2021b. In addition, the copresence of less hydrophilic phenolics with an intermediate amphipathic polarity in the polar lipid extracts of these apple extracts may provide additional antioxidant benefits too, since phenolics are a well-defined class of functional compounds against oxidative stress and associated disorders (Lee 2003; Lordan et al., 2019c;Tsoupras et al. 2009Tsoupras et al. , 2018. ...
... Apart from their functional properties on cider sensory characteristics, apple cider phenolics have been found to display several bioactive functions too, with the most well-established being their antioxidant potency. The beneficial antioxidant effects and associated health benefits of phenolics have been reviewed thoroughly (Lee 2003;Lordan et al., 2019c;Tsoupras et al. 2009Tsoupras et al. , 2018. The literature displays a clear correlation between diets rich in fruits and polyphenols and the reduction of inflammatory manifestations linked to chronic diseases such as atherosclerosis (Woodside 2013). ...
... This process could potentially occur in the small intestine, which means the number of phenolic compounds in a beer may not necessarily indicate the level of antioxidant capacity and therefore, a greater variety of phenolic compounds may be desirable to benefit from their intake. Consideration also must also be paid to the absorbability and the metabolism of phenolics, for which there is evidence that some phenolics have bioavailability issues, particularly in beer, which has both bound and free phenolics (Crozier et al., 2009;Lordan et al., 2019c;Nardini & Ghiselli, 2004). ...
... In contrast to the water-soluble extracts of apples that showed very little to no antiplatelet effects, it was recently found that apples, apple juice, and apple cider contain several polar lipid bioactives, which have shown strong anti-inflammatory and antiplatelet functional properties Tsoupras et al. 2021aTsoupras et al. , 2021b. In addition, the copresence of less hydrophilic phenolics with an intermediate amphipathic polarity in the polar lipid extracts of these apple extracts may provide additional antioxidant benefits too, since phenolics are a well-defined class of functional compounds against oxidative stress and associated disorders (Lee 2003; Lordan et al., 2019c;Tsoupras et al. 2009Tsoupras et al. , 2018. ...
... Apart from their functional properties on cider sensory characteristics, apple cider phenolics have been found to display several bioactive functions too, with the most well-established being their antioxidant potency. The beneficial antioxidant effects and associated health benefits of phenolics have been reviewed thoroughly (Lee 2003;Lordan et al., 2019c;Tsoupras et al. 2009Tsoupras et al. , 2018. The literature displays a clear correlation between diets rich in fruits and polyphenols and the reduction of inflammatory manifestations linked to chronic diseases such as atherosclerosis (Woodside 2013). ...
... This process could potentially occur in the small intestine, which means the number of phenolic compounds in a beer may not necessarily indicate the level of antioxidant capacity and therefore, a greater variety of phenolic compounds may be desirable to benefit from their intake. Consideration also must also be paid to the absorbability and the metabolism of phenolics, for which there is evidence that some phenolics have bioavailability issues, particularly in beer, which has both bound and free phenolics (Crozier et al., 2009;Lordan et al., 2019c;Nardini & Ghiselli, 2004). ...
It is now well established that moderate consumption of fermented alcoholic beverages, as part of a well-balanced diet, provides several health benefits. Apart from wine, moderate consumption of beer and apple cider has also been proposed for a plethora of health benefits, such as a decrease in oxidative stress, thrombosis, inflammation, and lowering of biomarkers associated with risk of cardiovascular disorders, coronary heart disease, ischaemic stroke, and total mortality. Within this chapter, the functional properties and benefits of the fermented alcoholic beverages, beer and apple cider, are thoroughly reviewed. Emphasis is given to their content in bio-functional antioxidant and anti-inflammatory compounds, their probiotics' content, and the effects of fermentation on their association with the observed health benefits of these functional beverages. Current and future strategies for the utilization of these compounds and probiotics, along with appropriate modifications of the fermentation processes, for the production of novel functional products with enhanced beneficial effects against chronic disorders are also thoroughly presented.
... Thus, the pathway regulating lipid metabolic reprogramming has emerged as an important potential target for tumour therapy (49). Lipid droplets play an important role in the process of lipid metabolism and are the central hub for processing lipids (48). Lipid droplets are spherical monolayer organelles that primarily regulate lipid metabolism, transport and signalling in cells and tissues (50). ...
Background
Gastric cancer is one of the common malignant tumors of the digestive system worldwide, posing a serious threat to human health. A growing number of studies have demonstrated the important role that lipid droplets play in promoting cancer progression. However, few studies have systematically evaluated the role of lipid droplet metabolism-related genes (LDMRGs) in patients with gastric cancer.
Methods
We identified two distinct molecular subtypes in the TCGA-STAD cohort based on LDMRGs expression. We then constructed risk prediction scoring models in the TCGA-STAD cohort by lasso regression analysis and validated the model with the GSE15459 and GSE66229 cohorts. Moreover, we constructed a nomogram prediction model by cox regression analysis and evaluated the predictive efficacy of the model by various methods in STAD. Finally, we identified the key gene in LDMRGs, ABCA1, and performed a systematic multi-omics analysis in gastric cancer.
Results
Two molecular subtypes were identified based on LDMRGs expression with different survival prognosis and immune infiltration levels. lasso regression models were effective in predicting overall survival (OS) of gastric cancer patients at 1, 3 and 5 years and were validated in the GEO database with consistent results. The nomogram prediction model incorporated additional clinical factors and prognostic molecules to improve the prognostic predictive value of the current TNM staging system. ABCA1 was identified as a key gene in LDMRGs and multi-omics analysis showed a strong correlation between ABCA1 and the prognosis and immune status of patients with gastric cancer.
Conclusion
This study reveals the characteristics and possible underlying mechanisms of LDMRGs in gastric cancer, contributing to the identification of new prognostic biomarkers and providing a basis for future research.
... They have also been implicated in many of the key processes that lead to the development of atherosclerosis. However, researchers over the years have postulated that dietary PAF-R antagonists may affect PAF-related signalling and inflammatory pathways [7,17,18]. This has opened several avenues of research that aim to investigate certain dietary patterns such as the Mediterranean diet, which is thought to offer protection from atherosclerotic cardiovascular disease and other inflammatory diseases due to a high concentration of these compounds in the diet [18,19]. ...
Platelet-activating factor (PAF) is a lipid mediator that interacts with its receptor (PAF-R) to carry out cell signalling. However, under certain conditions the binding of PAF to PAF-R leads to the activation of pro-inflammatory and prothrombotic pathways that have been implicated in the onset and development of atherosclerotic cardiovascular diseases (CVD) and inflammatory diseases. Over the past four decades, research has focused on the identification and development of PAF-R antagonists that target these inflammatory diseases. Research has also shown that dietary factors such as polar lipids, polyphenols, and other nutrient constituents may affect PAF metabolism and PAF-R function through various mechanisms. In this review we focus on the inhibition of PAF-R and how this may contribute to reducing cardiovascular disease risk. We conclude that further development of PAF-R inhibitors and human studies are required to investigate how modulation of the PAF-R may prevent the development of atherosclerotic cardiovascular disease and may lead to the development of novel therapeutics.
