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Acetate Metabolism in Physiology, Cancer, and Beyond.
Bose, S, Ramesh, V, Locasale, JW
Trends in cell biology. 2019;(9):695-703
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Abstract
Acetate and the related metabolism of acetyl-coenzyme A (acetyl-CoA) confer numerous metabolic functions, including energy production, lipid synthesis, and protein acetylation. Despite its importance as a nutrient for cellular metabolism, its source has been unclear. Recent studies have provided evidence to support the existence of a de novo pathway for acetate production derived from pyruvate, the end product of glycolysis. This mechanism of pyruvate-derived acetate generation could have far-reaching implications for the regulation of central carbon metabolism. In this Opinion, we discuss our current understanding of acetate metabolism in the context of cell-autonomous metabolic regulation, cell-cell interactions, and systemic physiology. Applications relevant to health and disease, particularly cancer, are emphasized.
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Molecular mechanism of plant stress hormone methyl jasmonate for its anti-inflammatory activity.
Gunjegaonkar, SM, Shanmugarajan, TS
Plant signaling & behavior. 2019;(10):e1642038
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Abstract
Plant stress hormones (Phytohormones/PTH) are abundantly present in numerous vascular plants. Several classes of plant stress hormones like auxins (AU) & gibberellins (GA), cytokinins (CK), abscisic acid (ABA), ethylene (ET), salicylic acid (SA), jasmonates (JA), brassinosteroids (BR) and strigolactones are synthesized within specialized plant cells. Among them, jasmonate are prominent class of stress hormones involved in survival of plants in stressful conditions. Methyl jasmonate (MeJA) is ester of jasmonic acid is extensively studied for its potential clinical benefits. MeJA is used as an effective antimicrobial agent, food preservative, antioxidant in food and agricultural sectors. The clinical benefits of MeJA have been related to their prominent interactions with inflammatory NF-κB pathways, inhibition of enzymes, gene expression for synthesis of inflammatory mediators, signaling molecules, oxidative stress and modulation of pain perception/nociceptive responses. The objective of the present review is to provide an cohesive relation of MeJA in inflammation with reference to past and recent in-vivo and in-vitro investigations in broad perspectives.
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Changing dialysate composition to optimize acid-base therapy.
Sargent, JA, Marano, M, Marano, S, Gennari, FJ
Seminars in dialysis. 2019;(3):248-254
Abstract
In response to rapid alkali delivery during hemodialysis, hydrogen ions (H+ ) are mobilized from body buffers and from stimulation of organic acid production in amounts sufficient to convert most of the delivered bicarbonate to CO2 and water. Release of H+ from nonbicarbonate buffers serves to back-titrate them to a more alkaline state, readying them to buffer acids that accumulate in the interval between treatments. By contrast, stimulation of organic acid production only serves to remove added bicarbonate (HCO3 - ) from the body; the organic anions produced by this process are lost into the dialysate, irreversibly acidifying the patient as well as diverting metabolic activity from normal homeostasis. We have developed an analytic tool to quantify these acid-base events, which has shown that almost two-thirds of the H+ mobilized during hemodialysis comes from organic acid production when bath bicarbonate concentration ([HCO3 - ]) is 32 mEq/L or higher. Using data from the hemodialysis patients we studied with our analytical model, we have simulated the effect of changing bath solute on estimated organic acid production. Our simulations demonstrate that reducing bath [HCO3 - ] should decrease organic acid production, a change we propose as beneficial to the patient. They also highlight the differential effects of variations in bath acetate concentration, as compared to [HCO3 - ], on the amount and rate of alkali delivery. Our results suggest that transferring HCO3 - delivery from direct influx to acetate influx and metabolism provides a more stable and predictable rate of HCO3 - addition to the patient receiving bicarbonate-based hemodialysis. Our simulations provide the groundwork for the clinical studies needed to verify these conclusions.
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Question 2: Is there a role for Montelukast in the management of viral-induced wheeze in preschool children?
Burman, A
Archives of disease in childhood. 2018;(5):519-520
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Targeting cysteinyl-leukotrienes in abdominal aortic aneurysm.
Araújo, AC, Tang, X, Haeggström, JZ
Prostaglandins & other lipid mediators. 2018;:24-28
Abstract
Abdominal aortic aneurysm (AAA) is an asymptomatic dilatation of the vessel wall exceeding the normal vessel diameter by 50%, accompanied by intramural thrombus formation. Since the aneurysm can rupture, AAA is a life-threatening vascular disease, which may be amenable to surgical repair. At present, no pharmacological therapy for AAA is available. The 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism leads to biosynthesis of leukotrienes (LTs), potent lipid mediators with pro-inflammatory biological actions. Among the LTs, cysteinyl-leukotrienes (cys-LT) are well-recognized signaling molecules in human asthma and allergic rhinitis. However, the effects of these molecules in cardiovascular diseases have only recently been explored. Drugs antagonizing the CysLT1 receptor, termed lukasts and typified by montelukast, are established therapeutics for clinical management of asthma. Lukasts are safe, well-tolerated drugs that can be administered during long time periods. Here we describe recent data indicating that montelukast may be used for prevention and treatment of AAA, thus representing a promising pharmacological tool for a deadly vascular disease with significant socio-economic impact.
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Methyl Jasmonate: An Alternative for Improving the Quality and Health Properties of Fresh Fruits.
Reyes-Díaz, M, Lobos, T, Cardemil, L, Nunes-Nesi, A, Retamales, J, Jaakola, L, Alberdi, M, Ribera-Fonseca, A
Molecules (Basel, Switzerland). 2016;(6)
Abstract
Methyl jasmonate (MeJA) is a plant growth regulator belonging to the jasmonate family. It plays an important role as a possible airborne signaling molecule mediating intra- and inter-plant communications and modulating plant defense responses, including antioxidant systems. Most assessments of this compound have dealt with post-harvest fruit applications, demonstrating induced plant resistance against the detrimental impacts of storage (chilling injuries and pathogen attacks), enhancing secondary metabolites and antioxidant activity. On the other hand, the interactions between MeJA and other compounds or technological tools for enhancing antioxidant capacity and quality of fruits were also reviewed. The pleiotropic effects of MeJA have raisen numerous as-yet unanswered questions about its mode of action. The aim of this review was endeavored to clarify the role of MeJA on improving pre- and post-harvest fresh fruit quality and health properties. Interestingly, the influence of MeJA on human health will be also discussed.
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Leukotriene receptor antagonists as maintenance or intermittent treatment in pre-school children with episodic viral wheeze.
Brodlie, M, Gupta, A, Rodriguez-Martinez, CE, Castro-Rodriguez, JA, Ducharme, FM, McKean, MC
Paediatric respiratory reviews. 2016;:57-9
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The efficacy and safety of H1-antihistamine versus Montelukast for allergic rhinitis: A systematic review and meta-analysis.
Wei, C
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2016;:989-997
Abstract
PURPOSE In order to verify the differences of effectiveness and safety between SAHs and Montelukast, and to find out potential uncared-for problems, we performed a systematic review and Meta-analysis to proceed a qualitative describe and quantitative assessment. METHODS We searched the databases of Pubmed, the Cochrane Library, Nature and Science as well as Wanfang data and CNKI from 2000 to March 2016, using key words "Montelukast SAH" or "H1-antihistamine Montelukast", or "Loratadine Montelukast", or "Desloratadine Montelukast", or "Levocetirizine Montelukast", or "Cetirizen Montelukast", or "Fexofenadine Montelukast". And also we included studies through relevant citations in related literature. Meta-analysis and bias of risk were performed. We analyzed Heterogeneity and publish bias as well. RESULT Montelukast seems more effective in nighttime symptoms compare with SAHs (P=0.008, MD=-0.04, 95%CI: -0.08, -0.01). No significant difference was found between Montelukast and SAHs in CSS (P=0.10, MD=0.03, 95%CI: -0.01, 0.07). Montelukast and SAHs combined therapy was more effective than Montelukast DNSS (P=0.0006, MD=0.15, 95%CI: 0.07, 0.24) but not in CSS (P=0.04, MD=0.08, 95%CI: 0.00, 0.15; Bonferroni correction α=0.017). CONCLUSION Montelukast has a significant influence in improving patients' nasal symptoms quality of live but is not as effective as SAHs, and may have a slight advantage over SAHs in relieving nighttime symptoms significantly. Combined therapy is more effective in improving patients' day time symptom than Montelukast. Probably, patients might have a lower asthenia incidence rate when using Montelukas.
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The metabolic fate of acetate in cancer.
Schug, ZT, Vande Voorde, J, Gottlieb, E
Nature reviews. Cancer. 2016;(11):708-717
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Abstract
Recent high-profile reports have reignited an interest in acetate metabolism in cancer. Acetyl-CoA synthetases that catalyse the conversion of acetate to acetyl-CoA have now been implicated in the growth of hepatocellular carcinoma, glioblastoma, breast cancer and prostate cancer. In this Review, we discuss how acetate functions as a nutritional source for tumours and as a regulator of cancer cell stress, and how preventing its (re)capture by cancer cells may provide an opportunity for therapeutic intervention.
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Intensive Hemodialysis, Mineral and Bone Disorder, and Phosphate Binder Use.
Copland, M, Komenda, P, Weinhandl, ED, McCullough, PA, Morfin, JA
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2016;(5S1):S24-S32
Abstract
Mineral and bone disorder is a common complication of end-stage renal disease. Notably, hyperphosphatemia likely promotes calcification of the myocardium, valves, and arteries. Hyperphosphatemia is associated with higher risk for cardiovascular mortality and morbidity along a gradient beginning at 5.0mg/dL. Among contemporary hemodialysis (HD) patients, mean serum phosphorus level is 5.2mg/dL, although 25% of patients have serum phosphorus levels of 5.5 to 6.9mg/dL; and 13%, >7.0mg/dL. Treatment of hyperphosphatemia is burdensome. Dialysis patients consume a mean of 19 pills per day, half of which are phosphate binders. Medicare Part D expenditures on binders for dialysis patients approached $700 million in 2013. Phosphorus removal with thrice-weekly HD (4 hours per session) is ∼3,000mg/wk. However, clearance is unlikely to counterbalance dietary intake, which varies around a mean of 7,000mg/wk. Dietary restriction and phosphate binders are important interventions, but each has limitations. Dietary control is complicated by limited access to healthy food choices and unclear labeling. Meanwhile, adherence to phosphate binders is poor, especially in younger patients and those with high pill burden. Multiple randomized clinical trials show that intensive HD reduces serum phosphorus levels. In the Frequent Hemodialysis Network (FHN) trial, short daily and nocturnal schedules reduced serum phosphorus levels by 0.6 and 1.6mg/dL, respectively, relative to 3 sessions per week. A similar effect of nocturnal HD was observed in an earlier trial. In the daily arm of the FHN trial, intensive HD significantly lowered estimated phosphate binder dose per day, whereas in the nocturnal arm, intensive HD led to binder discontinuation in 75% of patients. However, intensive HD appears to have no meaningful effects on serum calcium and parathyroid hormone concentrations. In conclusion, intensive HD, especially nocturnal HD, lowers serum phosphorus levels and decreases the need for phosphate binders.