Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease (CVD) risk factors such as atherosclerosis, inflammation, obesity, ...insulin resistance, platelet hyperactivity, and plasma lipid abnormalities. Several studies in humans and animal models have demonstrated an association between gut microbial metabolites such as trimethylamine-
-oxide (TMAO), short-chain fatty acids, and bile acid metabolites (amino acid breakdown products) with CVD. Human blood platelets are a critical contributor to the hemostatic process. Besides, these blood cells play a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. Since the TMAO, and other metabolites of the gut microbiota, are asociated with platelet hyperactivity, lipid disorders, and oxidative stress, the diet-gut microbiota interactions have become an important research area in the cardiovascular field. The gut microbiota and their metabolites may be targeted for the therapeutic benefit of CVD from a clinical perspective. This review's main aim is to highlight the complex interactions between microbiota, their metabolites, and several CVD risk factors.
The endothelium acts as the barrier that prevents circulating lipids such as lipoproteins and fatty acids into the arterial wall; it also regulates normal functioning in the circulatory system by ...balancing vasodilation and vasoconstriction, modulating the several responses and signals. Plasma lipids can interact with endothelium via different mechanisms and produce different phenotypes. Increased plasma-free fatty acids (FFAs) levels are associated with the pathogenesis of atherosclerosis and cardiovascular diseases (CVD). Because of the multi-dimensional roles of plasma FFAs in mediating endothelial dysfunction, increased FFA level is now considered an essential link in the onset of endothelial dysfunction in CVD. FFA-mediated endothelial dysfunction involves several mechanisms, including dysregulated production of nitric oxide and cytokines, metaflammation, oxidative stress, inflammation, activation of the renin-angiotensin system, and apoptosis. Therefore, modulation of FFA-mediated pathways involved in endothelial dysfunction may prevent the complications associated with CVD risk. This review presents details as to how endothelium is affected by FFAs involving several metabolic pathways.
During pregnancy, maternal plasma fatty acids are critically required for cell growth and development, cell signaling, and the development of critical structural and functional aspects of the ...feto-placental unit. In addition, the fatty acids modulate the early stages of placental development by regulating angiogenesis in the first-trimester human placenta. Preferential transport of maternal plasma long-chain polyunsaturated fatty acids during the third trimester is critical for optimal fetal brain development. Maternal status such as obesity, diabetes, and dietary intakes may affect the functional changes in lipid metabolic processes in maternal-fetal lipid transport and metabolism. Fatty acids traverse the placental membranes
several plasma membrane fatty acid transport/binding proteins (FAT, FATP, p-FABPpm, and FFARs) and cytoplasmic fatty acid-binding proteins (FABPs). This review discusses the maternal metabolism of fatty acids and their effects on early placentation, placental fatty acid transport and metabolism, and their roles in feto-placental growth and development. The review also highlights how maternal fat metabolism modulates lipid processing, including transportation, esterification, and oxidation of fatty acids.
The dysregulation of fat metabolism is involved in various disorders, including neurodegenerative, cardiovascular, and cancers. The uptake of long-chain fatty acids (LCFAs) with 14 or more carbons ...plays a pivotal role in cellular metabolic homeostasis. Therefore, the uptake and metabolism of LCFAs must constantly be in tune with the cellular, metabolic, and structural requirements of cells. Many metabolic diseases are thought to be driven by the abnormal flow of fatty acids either from the dietary origin and/or released from adipose stores. Cellular uptake and intracellular trafficking of fatty acids are facilitated ubiquitously with unique combinations of fatty acid transport proteins and cytoplasmic fatty acid-binding proteins in every tissue. Extensive data are emerging on the defective transporters and metabolism of LCFAs and their clinical implications. Uptake and metabolism of LCFAs are crucial for the brain's functional development and cardiovascular health and maintenance. In addition, data suggest fatty acid metabolic transporter can normalize activated inflammatory response by reprogramming lipid metabolism in cancers.
Here we review the current understanding of how LCFAs and their proteins contribute to the pathophysiology of three crucial diseases and the mechanisms involved in the processes.
Copper (Cu) is an essential micronutrient for both pathogens and the hosts during viral infection. Cu is involved in the functions of critical immune cells such as T helper cells, B cells, ...neutrophils natural killer (NK) cells, and macrophages. These blood cells are involved in the killing of infectious microbes, in cell-mediated immunity and the production of specific antibodies against the pathogens. Cu-deficient humans show an exceptional susceptibility to infections due to the decreased number and function of these blood cells. Besides, Cu can kill several infectious viruses such as bronchitis virus, poliovirus, human immunodeficiency virus type 1(HIV-1), other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Moreover, Cu has the potent capacity of contact killing of several viruses, including SARS‐CoV‐2. Since the current outbreak of the COVID-19 continues to develop, and there is no vaccine or drugs are currently available, the critical option is now to make the immune system competent to fight against the SARS‐CoV‐2. Based on available data, we hypothesize that enrichment of plasma copper levels will boost both the innate and adaptive immunity in people. Moreover, owing to its potent antiviral activities, Cu may also act as a preventive and therapeutic regime against COVID-19.
•Maternal fatty acids are essential for the growth and development of feto-placental unit. Maternal fatty acids modulate growth and development of trophoblast cell, and structural & functional ...aspects of the placenta and the fetus.•Long-chain fatty acids augment angiogenesis of the first-trimester placenta by stimulating vascular endothelium growth factor (VEGF), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding proteins (FABPs), or their eicosanoid metabolites.•Placental preferential transport of maternal plasma long-chain polyunsaturated fatty acids during the last trimester is critically essential for the development of brain and retina of the fetus.•Transport of maternal fatty acids to the fetus is partly mediated by plasma membrane fatty acid transport system (FAT, FATPs, p-FABPpm, & placental MFSD2a) and cytoplasmic FABPs.•Maternal lifestyle such as obesity, diet, metabolic states, inflammation and endocrine factors can impair placental function via altered expression of placental fatty acid transporters that lead to pregnancy complications and compromised fetal outcome.
Fatty acids are essential for feto-placental growth and development. Maternal fatty acids and their metabolites are involved in every stage of pregnancy by supporting cell growth and development, cell signaling, and modulating other critical aspects of structural and functional processes. Early placentation process is critical for placental growth and function. Several fatty acids modulate angiogenesis as observed by increased tube formation and secretion of angiogenic growth factors in first-trimester human placental trophoblasts. Long-chain fatty acids stimulate angiogenesis in these cells via vascular endothelium growth factor (VEGF), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding proteins (FABPs), or eicosanoids. Inadequate placental angiogenesis and trophoblast invasion of the maternal decidua and uterine spiral arterioles leads to structural and functional deficiency of placenta, which contributes to preeclampsia, pre-term intrauterine growth restriction, and spontaneous abortion and also affects overall fetal growth and development. During the third trimester of pregnancy, placental preferential transport of maternal plasma long-chain polyunsaturated fatty acids is of critical importance for fetal growth and development. Fatty acids cross the placental microvillous and basal membranes by mainly via plasma membrane fatty acid transport system (FAT, FATP, p-FABPpm, & FFARs) and cytoplasmic FABPs. Besides, a member of the major facilitator superfamily-MFSD2a, present in the placenta is involved in the supply of DHA to the fetus. Maternal factors such as diet, obesity, endocrine, inflammation can modulate the expression and activity of the placental fatty acid transport activity and thereby impact feto-placental growth and development.
In this review, we discuss the maternal dietary fatty acids, and placental transport and metabolism, and their roles in placental growth and development.
Colon cancer is the third most predominant cancer caused by genetic, environmental and nutritional factors. Plant-based compounds are very well known to regress colon cancer in many ways, like ...delaying tumor growth, managing chemotherapy and radiation therapy side-effects, and working at the molecular levels. Medicinal plants contain many bioactive phytochemicals such as flavonoids, polyphenol compounds, caffeic acid, catechins, saponins, polysaccharides, triterpenoids, alkaloids, glycosides, phenols, quercetin, luteolin, kaempferol and luteolin glycosides, carnosic acid, oleanolic acid, rosmarinic acid, emodin, and eugenol and anthricin. These bioactive compounds can reduce tumor cell proliferation via several mechanisms, such as blocking cell cycle checkpoints and promoting apoptosis through activating initiator and executioner caspase. Traditional medicines have been used globally to treat cancers because of their anti-cancer effects, antioxidant properties, anti-inflammatory properties, anti-mutagenic effects, and anti-angiogenic effects. In addition, these medicines effectively suppress early and intermediate stages of carcinogenesis when administered in their active and pure form. However, traditional medicine is not very popular due to some critical challenges. These include poor solubility and absorption of these compounds, intellectual property-related issues, involvement of drug synergism, absence of drug-likeness, and unsure protocols for their extraction from the plant source. Using bioactive compounds in colon cancer has equal advantages and limitations. This review highlights the benefits and challenges of using bioactive compounds derived from plants for colon cancer. We have also discussed using these compounds to target cancer stem cell self-renewal, its effects on cancer cell metabolism, safety parameters, easy modulation, and their bioavailability.
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•Bioactive compounds suppress carcinogenesis at various stages of colon cancer.•Bioactive compounds can induce apoptosis and cell cycle arrest.•Bioactive compounds have anti-inflammatory and anti-oxidant activities.•Bioactive compounds modulate the JNK, STAT, PI3K/AKT/mTOR and MAPK pathways.•Bioactive compounds have lack drug-likeness and low bioavailability.
Cells are continually exposed to reactive oxygen species (ROS) generated during cellular metabolism. Apoptosis, necrosis, and autophagy are biological processes involving a feedback cycle that causes ...ROS molecules to induce oxidative stress. To adapt to ROS exposure, living cells develop various defense mechanisms to neutralize and use ROS as a signaling molecule. The cellular redox networks combine signaling pathways that regulate cell metabolism, energy, cell survival, and cell death. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) are essential antioxidant enzymes that are required for scavenging ROS in various cell compartments and response to stressful situations. Among the non-enzymatic defenses, vitamin C, glutathione (GSH), polyphenols, carotenoids, vitamin E, etc., are also essential. This review article describes how ROS are produced as byproducts of oxidation/reduction (redox) processes and how the antioxidants defense system is directly or indirectly engaged in scavenging ROS. In addition, we used computational methods to determine the comparative profile of binding energies of several antioxidants with antioxidant enzymes. The computational analysis demonstrates that antioxidants with a high affinity for antioxidant enzymes regulate their structures.
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•Cells are continually generated and exposed to reactive oxygen species (ROS).•Living cells develop defense mechanisms to neutralize ROS and use it as a signaling molecule.•The computational methods determine the comparative profile of binding energies of several antioxidants with antioxidant enzymes.•The computational analysis demonstrates that antioxidants with a high affinity for antioxidant enzymes regulate their structures.
This Special Issue of Nutrients, “Influence of Maternal Diet and Environmental Factors on Fetal Development”, requests articles on the roles of maternal diet and environmental factors such as ...microbiota, plastics, and endocrine disruptive chemicals impact fetal development ...
Essential fatty acids and their long chain polyunsaturated fatty acid derivatives (20C) such as docosahexaenoic and arachidonic acids are critical for proper fetal growth and development. Dietary ...intake as well as metabolism of these fatty acids, and their subsequent transfer from the mother to the fetus are therefore important requisites for developing fetus. The placenta is the key organ through which nutrients such as these fatty acids flow from the mother to the fetus. Cellular uptake and translocation of long chain fatty acids (LCFAs) in different tissues is achieved by a concert of co-existing mechanism. Although LCFA can enter the cell via passive diffusion, emerging reports indicate that LCFA uptake is tightly regulated by several plasma membrane-located transport/binding proteins such as fatty acid translocase (FAT/CD36), plasma membrane fatty acid binding protein (FABPpm), fatty acid transport protein (FATP) and intracellular FABPs in several tissues including human placenta. Fatty acid activated transcription factors (PPARs, LXR, RXR, and SREBP-1) have been demonstrated to regulate these fatty acid transport/binding proteins, and placental functions. Maternal fatty acids therefore may regulate their own placental transport as well as placental function via several fatty acid-activated transcription factors. This review summarizes recent developments on placental fatty acid transport and metabolisms, and the regulatory roles of these proteins in these processes.
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