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The New England Journal of Medicine Apr 2023
Topics: Humans; Dicarboxylic Acids; Fatty Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents
PubMed: 36876748
DOI: 10.1056/NEJMe2301490 -
ChemSusChem Jan 2022Adipic acid (AA) is a key industrial dicarboxylic acid intermediate used in nylon manufacturing. Unfortunately, the traditional process technology is accompanied by... (Review)
Review
Adipic acid (AA) is a key industrial dicarboxylic acid intermediate used in nylon manufacturing. Unfortunately, the traditional process technology is accompanied by serious environmental pollution. Given the growing demand for adipic acid and the desire to reduce its negative impact on the environment, considerable efforts have been devoted to developing more green and friendly routes. This Review is focused on the latest advances in the sustainable preparation of AA from biomass-based platform molecules, including 5-hydroxymethylfufural, glucose, γ-valerolactone, and phenolic compounds, through biocatalysis, chemocatalysis, and the combination of both. Additionally, the development of state-of-the-art catalysts for different catalytic systems systematically is discussed and summarized, as well as their reaction mechanisms. Finally, the prospects for all preparation routes are critically evaluated and key technical challenges in the development of green and sustainable processes for the manufacture of AA are highlighted. It is hoped that the green adipic acid synthesis pathways presented can provide insights and guidance for further research into other industrial processes for the production of nylon precursors in the future.
Topics: Adipates; Biocatalysis; Biomass; Catalysis
PubMed: 34716751
DOI: 10.1002/cssc.202101531 -
Molecules (Basel, Switzerland) Jun 2022The most versatile furanic building block for chemical and polymer applications is 2,5-furandicarboxylic acid. However, the classical 2,5-furandicarboxylic acid... (Review)
Review
The most versatile furanic building block for chemical and polymer applications is 2,5-furandicarboxylic acid. However, the classical 2,5-furandicarboxylic acid production methodology has been found to have significant drawbacks that hinder industrial-scale production. This review highlights new alternative methods to synthesize 2,5-furandicarboxylic acid that are both more advantageous and attractive than conventional oxidation of 5-hydroxymethylfurfural. This review also focuses on the use of 2,5-furandicarboxylic acid as a polymer precursor and the various potential applications that arise from these furan-based materials.
Topics: Dicarboxylic Acids; Furans; Oxidation-Reduction; Polymers
PubMed: 35807313
DOI: 10.3390/molecules27134071 -
Biotechnology Advances 2021Dicarboxylic acids (DCAs) are important commodity chemicals which have been widely applied in polymer, food and pharmaceutical industries. Biosynthesis of DCAs from... (Review)
Review
Dicarboxylic acids (DCAs) are important commodity chemicals which have been widely applied in polymer, food and pharmaceutical industries. Biosynthesis of DCAs from renewable carbon sources represents a promising alternative to chemical synthesis. Over the years, the recombinant strains have been constructed to produce an increasing number of DCAs. In this review, recent advances on the microbial synthesis of various DCAs have been summarized and categorized into three groups: the tricarboxylic acid cycle-derived, lysine metabolism-related, and aromatic compounds degradation-derived DCAs. We focused mainly on the metabolic engineering and synthetic biology strategies for improving the production efficiency, including metabolic flux analysis, fine-tuning of gene expression, cofactor balancing, metabolic compartmentalization, dynamic regulation and co-culture to regulate the production at multiple levels. The current challenges and perspectives have also been discussed.
Topics: Citric Acid Cycle; Dicarboxylic Acids; Metabolic Engineering; Organic Chemicals
PubMed: 33582180
DOI: 10.1016/j.biotechadv.2021.107710 -
Journal of Clinical Lipidology 2024Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins.
OBJECTIVE
To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies.
METHODS
CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years.
RESULTS
In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups.
CONCLUSIONS
Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
Topics: Humans; Cardiovascular Diseases; Cholesterol; Dicarboxylic Acids; Fatty Acids; Heart Disease Risk Factors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Risk Factors; Double-Blind Method
PubMed: 37951797
DOI: 10.1016/j.jacl.2023.10.011 -
Molecules (Basel, Switzerland) Apr 2022A -(2-methoxy-2-oxoethyl)--(phenylsulfonyl)glycine monomethyl ester of the respective dicarboxylic acid was involved in a reaction with imines promoted by acetic...
A -(2-methoxy-2-oxoethyl)--(phenylsulfonyl)glycine monomethyl ester of the respective dicarboxylic acid was involved in a reaction with imines promoted by acetic anhydride at an elevated temperature. Instead of the initially expected δ-lactam products of the Castagnoli-Cushman-type reaction, medicinally important 3-amino-2-azetidinones were obtained as the result of cyclization, involving a methylene group adjacent to an acid moiety. In contrast, replacing alcohol residue with hexafluoroisopropyl in the same substrate made another methylene group (adjacent to the ester moiety) more reactive to furnishing the desired δ-lactam in the Castagnoli-Cushman fashion.
Topics: Cyclization; Dicarboxylic Acids; Esters; Imines; Lactams
PubMed: 35458663
DOI: 10.3390/molecules27082469 -
Journal of Evidence-based Medicine Nov 2020The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects...
Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review.
OBJECTIVE
The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects of these topical treatments by collecting randomized controlled trials.
METHODS
We searched The Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS up to May 2019. We also searched five trials registers. Two review authors independently extracted data and assessed risk of bias. Meta analyses were performed by using Review Manager 5 software.
RESULTS
We included a total of 49 trials involving 3880 participants. In terms of treatment response (measured using participants' global self-assessment of acne improvement, PGA), azelaic acid was probably less effective than benzoyl peroxide (RR = 0.82, 95% CI 0.72-0.95). However, there was probably little or no difference in PGA when comparing azelaic acid to tretinoin (RR = 0.94, 95% CI 0.78-1.14). There may be little or no difference when comparing salicylic acid to tretinoin (RR = 1.00, 95% CI 0.92-1.09). There were no studies measured PGA when evaluating nicotinamide. With respect to alpha-hydroxy acid, there may be no difference in PGA when comparing glycolic acid to salicylic-mandelic acid (RR = 1.06, 95% CI 0.88-1.26). We were uncertain about the effects of sulfur and zinc. Adverse events associated with these topical treatments were always mild and transient.
CONCLUSIONS
Moderate-quality evidence was available for azelaic acid and low- to very-low-quality evidence for other topical treatments. Risk of bias and imprecision limit our confidence in the evidence.
Topics: Acne Vulgaris; Administration, Cutaneous; Dermatologic Agents; Dicarboxylic Acids; Fruit; Glycolates; Humans; Niacinamide; Salicylic Acid; Sulfur; Treatment Outcome; Zinc
PubMed: 33034949
DOI: 10.1111/jebm.12411 -
Lipids in Health and Disease May 2020In the last 50 years, several clinical and epidemiological studies during have shown that increased levels of low-density lipoprotein cholesterol (LDLc) are associated... (Review)
Review
In the last 50 years, several clinical and epidemiological studies during have shown that increased levels of low-density lipoprotein cholesterol (LDLc) are associated with the development and progression of atherosclerotic lesions. The discovery of β-Hydroxy β-methylglutaryl-CoA reductase inhibitors (statins), that possess LDLc-lowering effects, lead to a true revolution in the prevention and treatment of cardiovascular diseases. Statins remain the cornerstone of LDLc-lowering therapy. Lipid-lowering drugs, such as ezetimibe and bile acid sequestrants, are prescribed either in combination with statins or in monotherapy (in the setting of statin intolerance or contraindications to statins). Microsomal triglyceride transfer protein inhibitors and protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are other drug classes which have been investigated for their potential to decrease LDLc. PCSK9 have been approved for the treatment of hypercholesterolemia and for the secondary prevention of cardiovascular events. The present narrative review discusses the latest (2019) guidelines of the European Atherosclerosis Society/European Society of Cardiology for the management of dyslipidemia, focusing on LDLc-lowering drugs that are either already available on the market or under development. We also consider "whom, when and how" do we treat in terms of LDLc reduction in the daily clinical practice.
Topics: Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atherosclerosis; Benzimidazoles; Bile Acids and Salts; Carrier Proteins; Cholesterol, LDL; Dicarboxylic Acids; Europe; Ezetimibe; Fatty Acids; Gene Expression; Guidelines as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; RNA, Small Interfering
PubMed: 32375792
DOI: 10.1186/s12944-020-01275-x -
The American Journal of Cardiology Oct 2023Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%.... (Meta-Analysis)
Meta-Analysis
Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm.
Topics: Humans; Randomized Controlled Trials as Topic; Dicarboxylic Acids; Fatty Acids; Myocardial Infarction; Stroke
PubMed: 37633067
DOI: 10.1016/j.amjcard.2023.07.145 -
Current Opinion in Biotechnology Apr 2021New small molecules are continuing to emerge as metabolically derived regulators of cell function. Itaconate is a recent example where endogenous mammalian synthesis was... (Review)
Review
New small molecules are continuing to emerge as metabolically derived regulators of cell function. Itaconate is a recent example where endogenous mammalian synthesis was demonstrated only seven years ago. Since then, interest in the biochemistry and therapeutic potential of itaconate has grown dramatically. Itaconate is an unsaturated dicarboxylic acid that has antimicrobial properties and modulates metabolic pathways throughout the cell. Naturally occurring mutations of enzymes involved in human itaconate synthesis and degradation pathways are associated with disease susceptibility and immunity. Here, we highlight recent discoveries on itaconate metabolism and discuss the relevance of its evolutionary origin to its function in mammals. We also consider the therapeutic relevance of itaconate metabolism and its derivatives for treating metabolic and inflammatory diseases.
Topics: Animals; Humans; Metabolic Networks and Pathways; Succinates
PubMed: 33296743
DOI: 10.1016/j.copbio.2020.11.005