scholarly journals Role of fatty acids in inflammation, atherosclerosis, metabolic disorders and gout

2021 ◽  
Vol 15 (6) ◽  
pp. 124-129
Author(s):  
M. A. Gromova ◽  
V. V. Tsurko ◽  
O. A. Kislyak ◽  
E. V. Kiseleva
Keyword(s):  
Fatty Acids ◽  
Metabolic Disorders ◽  
Treatment Strategies ◽  
Endothelial Activation ◽  
Transport Systems ◽  
Membrane Phospholipids ◽  
Inflammatory Reactions ◽  
New Treatment ◽  
Urate Crystals

Fatty acids (FA) are present in all types of organisms and play an important role in energy metabolism. The length and number of double bonds in the FA of membrane phospholipids determine the viscosity, the activity of transport systems and enzymes, and also the susceptibility to lipid peroxidation. The review discusses the influence of free unsaturated FAs with short and long chains on various inflammatory mechanisms, including atherosclerosis. It has been shown that FAs can reduce endothelial activation and affect the metabolism of eicosanoids. A new model of fundamental factors determining the variability of the timing, degree and duration of acute inflammatory reactions in the deposition of urate crystals in tissues, in which FAs play an important role is considered, using gout as an example. In the future, the study of FAs will expand the understanding of the pathophysiology of chronic inflammation in various diseases, metabolic disorders and atherosclerosis and enable the development of new treatment strategies. 

scholarly journals Atherosclerosis, Dyslipidemia, and Inflammation: The Significant Role of Polyunsaturated Fatty Acids

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Mariarita Dessì ◽  
Annalisa Noce ◽  
Pierfrancesco Bertucci ◽  
Simone Manca di Villahermosa ◽  
Rossella Zenobi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Density Lipoprotein ◽  
Endothelial Activation ◽  
Transport Systems ◽  
Low Grade ◽  
Membrane Phospholipids ◽  
Membrane Structure And Function ◽  
Long Chain

Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed “eicosanoids,” which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have anti-inflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolism.

The Role of Inflammasomes in Atherosclerosis and Stroke Pathogenesis

2020 ◽  
Vol 26 (34) ◽  
pp. 4234-4245
Author(s):  
Deepaneeta Sarmah ◽  
Aishika Datta ◽  
Swapnil Raut ◽  
Ankan Sarkar ◽  
Birva Shah ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Treatment Strategies ◽  
Cerebrovascular Diseases ◽  
Cellular Injury ◽  
Inflammatory Reactions ◽  
Inflammatory Pathways

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators.

scholarly journals Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xu Zhou ◽  
Jingliang He ◽  
Jinbo Chen ◽  
Yu Cui ◽  
Zhenyu Ou ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Leydig Cells ◽  
Treatment Strategies ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Western Blots ◽  
New Treatment ◽  
Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

scholarly journals Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics

2021 ◽  
Vol 17 (9) ◽  
pp. e1009909
Author(s):  
Yushan Xia ◽  
Rubén Cebrián ◽  
Congjuan Xu ◽  
Anne de Jong ◽  
Weihui Wu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Treatment Strategies ◽  
Infection Model ◽  
Bacterial Cells ◽  
Membrane Phospholipids ◽  
Gram Negative ◽  
Atp Production ◽  
Rapid Spread ◽  
New Treatment ◽  
Multiple Antibiotics

The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. In this study, we show that a number of synthetic cationic peptides display strong synergistic antimicrobial effects with multiple antibiotics against the Gram-negative pathogen Pseudomonas aeruginosa. We found that an all-D amino acid containing peptide called D-11 increases membrane permeability by attaching to LPS and membrane phospholipids, thereby facilitating the uptake of antibiotics. Subsequently, the peptide can dissipate the proton motive force (PMF) (reduce ATP production and inhibit the activity of efflux pumps), impairs the respiration chain, promote the production of reactive oxygen species (ROS) in bacterial cells and induce intracellular antibiotics accumulation, ultimately resulting in cell death. By using a P. aeruginosa abscess infection model, we demonstrate enhanced therapeutic efficacies of the combination of D-11 with various antibiotics. In addition, we found that the combination of D-11 and azithromycin enhanced the inhibition of biofilm formation and elimination of established biofilms. Our study provides a realistic treatment option for combining close-to-nature synthetic peptide adjuvants with existing antibiotics to combat infections caused by P. aeruginosa.

Regulation Of The Fatty Acid Composition Of Platelet Phospholipids

1981 ◽  
Author(s):  
M L McKean ◽  
J B Smith ◽  
M J Silver
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Membrane Phospholipids ◽  
De Novo Biosynthesis ◽  
Coa Transferase

The fatty acid composition of cell membrane phospholipids does not remain constant after de novo biosynthesis, but undergoes continual remodelling. One of the major routes for remodelling probably includes the deacylation-reacylation steps of the Lands Pathway. This has been shown to be important for the incorporation of long chain, polyunsaturated fatty acids into phospholipids by liver and brain. An understanding of the mechanisms involved in these processes in platelets is especially important in light of the large stores of arachidonic acid (AA) in platelet phospholipids and the role of AA in hemostasis and thrombosis. Previous results from this laboratory have shown that the turnover of radioactive AA, 8,11,14-eicosatrienoic and 5,8,11,14,17-eicosapentaenoic acids in the phospholipids of resting platelets is more rapid than the turnover of radioactive C16 and C18 saturated and unsaturated fatty acids. However, little is known about how fatty acids, especially AA and its homologues, are incorporated into platelet phospholipids during de novo biosynthesis or how they are exchanged during remodelling.At least three enzymes are involved in the deacylation- reacylation of phospholipids: phospholipase A2; acyl CoA synthetase; and acyl CoA transferase. We have studied acyl CoA transferase and have found considerable activity in human platelet membranes. Experiments are in progress to determine the substrate specificity and other properties of this enzyme.

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

scholarly journals Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Financial Burden ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Inflammatory Reactions ◽  
Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies

2018 ◽  
Vol 4 (1-2) ◽  
Author(s):  
Preeti Singh
Keyword(s):  
Ischemic Stroke ◽  
New Technologies ◽  
Treatment Strategies ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Permanent Disability ◽  
Acute Cerebral Ischemia ◽  
Tremendous Progress ◽  
New Treatment

Ischemic stroke is a leading cause of death and permanent disability. This disease may affect any age group and especially in old age and pregnancy. All the responsible mechanisms are yet not completely understood. There is limited therapeutic intervention beyond prevention, yet tremendous progress in understanding cause of stroke at molecular level has been going on. A lot of advancement has occurred in the prevention and treatment of stroke during the past decade. In this review an update work of causeways of stroke and its therapeutic approaches have been discussed. The relevance of excitotoxicity (role of glutamate receptor), inflammation, ischemic penumbra, apoptosis, to delayed mechanisms and, damage and treatment strategies have been hasted out. Although the results among clinical studies, conflict regarding several experimental data of different therapies, and it may improve neurological outcome after acute cerebral ischemia. Along this several other interventions and new technologies such as stroke detector microwave helmet are being assessed and many other advanced techniques developed by researchers. Even the development of other novel and new treatment strategies (regarding molecular pathways and risk to benefit therapeutic ratio) for stroke are still required in future for better treatment.

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