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Journal of the American Heart... Aug 2013
Topics: Cardiovascular Diseases; Dairy Products; Dietary Fats; Fatty Acids; Female; Humans; Male; Phospholipids
PubMed: 23938288
DOI: 10.1161/JAHA.113.000393 -
International Journal of Pharmaceutics Mar 2023Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability....
Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability. However, HSA/drug nanocomplexes have to experience complicated manufacturing process including multiple high-pressure homogenization and removing organic solvent under reduced pressure condition. Besides, the clinical application of these HSA/drug nanocomplexes is often limited because of their unsatisfactory stability and restricted dose. To overcome these issues, a redox-responsive paclitaxel-pentadecanoic acid prodrug conjugate embedded human serum albumin nanoparticles (NPs) was developed as a model in this report. First, PTX was activated and conjugated with 11-mercaptoundecanoic acid through a disulfide bond. The resultant disulfide bond bridged paclitaxel-pentadecanoic acid conjugate (PTX-SS-C10-COOH) was characterized by NMR and MS. After that, PTX-SS-C10-COOH dissolved in ethanol was mixed with HSA in water followed by lyophilization to generate HSA/PTX-SS-C10-COOH nanoparticles (HPTX NPs). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) characterization indicated that the HPTX NPs have spherical structure with an average diameter of approximately 120 nm. The formation of HSA/PTX-SS-C10-COOH NPs was confirmed by fluorescence quenching technology, ascribed to electrostatic and hydrophobic interactions. The HPTX NPs displayed a highdrug loading of 29.78 % and an entrapment efficiency of 94.16 %. Their reduced responsiveness was validated by glutathione (GSH)-triggered fast release of PTX. The pharmacokinetics, antitumor efficacy and systemic toxicity of HPTX NPs were thoroughly evaluated. The results showed that the HPTX NPs had longer retention, more effective tumor growth inhibition and lower toxicity compared with commercialized Taxol®. Importantly, the HPTX NPs could be administered at much high dose to achieve a significant tumor growth inhibition compared with Abraxane®. Together, the redox-responsive HPTX NPs with high drug loading is a promising strategy to deliver PTX for cancer chemotherapy.
Topics: Humans; Paclitaxel; Serum Albumin, Human; Nanoparticles; Neoplasms; Oxidation-Reduction; Disulfides; Cell Line, Tumor
PubMed: 36822341
DOI: 10.1016/j.ijpharm.2023.122761 -
Molecules (Basel, Switzerland) Jan 2015The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain... (Review)
Review
The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain saturated fatty acids (OCS-FAs) were used as internal standards in GC-MS methods of total fatty acids and LC-MS methods of intact lipids, as it was thought their concentrations were insignificant in humans. However, it has been thought that increased consumption of dairy products has an association with an increase in blood plasma OCS-FAs. However, there is currently no direct evidence but rather a casual association through epidemiology studies. Furthermore, a number of studies on cardiometabolic diseases have shown that plasma concentrations of OCS-FAs are associated with lower disease risk, although the mechanism responsible for this is debated. One possible mechanism for the endogenous production of OCS-FAs is α-oxidation, involving the activation, then hydroxylation of the α-carbon, followed by the removal of the terminal carboxyl group. Differentiation human adipocytes showed a distinct increase in the concentration of OCS-FAs, which was possibly caused through α-oxidation. Further evidence for an endogenous pathway, is in human plasma, where the ratio of C15:0 to C17:0 is approximately 1:2 which is contradictory to the expected levels of C15:0 to C17:0 roughly 2:1 as detected in dairy fat. We review the literature on the dietary consumption of OCS-FAs and their potential endogenous metabolism.
Topics: Animals; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 2; Fatty Acids; Humans; Lipid Metabolism; Risk Factors
PubMed: 25647578
DOI: 10.3390/molecules20022425 -
International Journal of Cardiac Imaging Feb 1999beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid (BMIPP) is one of the branched-chain free fatty acids, which has suitable characteristics for myocardial SPECT because... (Review)
Review
beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid (BMIPP) is one of the branched-chain free fatty acids, which has suitable characteristics for myocardial SPECT because of higher uptake and longer retention in the myocardium. Recent advances of BMIPP myocardial SPECT for evaluating cardiomyopathy were reviewed. BMIPP defects were observed in 80% patients with hypertrophic cardiomyopathy (HCM). Moreover, BMIPP uptake was reduced at sites that corresponded with hypertrophic areas, where thallium uptake was increased. The correlations between severity score and septal wall thickness and LV function were better with BMIPP SPECT, suggesting that BMIPP is more suitable for the assessment of myocardial integrity in HCM. The dissociation between BMIPP and thallium defects was not observed frequently in dilated cardiomyopathy (DCM). We carried out BMIPP myocardial SPECT to evaluate the therapeutic effects of co-enzyme Q10 on DCM patients. Hearts to the mediastinum ratio and BMIPP defect scores were significantly decreased after co-enzyme Q10 treatment. BMIPP myocardial SPECT was confirmed to be sensitive in evaluating the therapeutic effect for the perspective of metabolic SPECT imaging. Recently, a lack of myocardial uptake of BMIPP has been found in a small subset of patients (0.3%-1.2%). Cardiac radionuclide imaging using BMIPP and 18F-FDG were performed on patients with type I CD36 deficiency. The percent dose uptake of 18F-FDG was significantly higher than in normal controls. CD functions as a major myocardial long-chain fatty acid transporter and its absence may lead to a compensatory upregulation of myocardial glucose uptake. An increased frequency of CD36 deficiency was demonstrated in cardiomyopathy. Therefore, fatty acid transport proteins and their related gene defects in relation to BMIPP uptake may become an important issue in the future.
Topics: Antioxidants; CD36 Antigens; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Coenzymes; Fatty Acids; Humans; Iodine Radioisotopes; Iodobenzenes; Tomography, Emission-Computed, Single-Photon; Ubiquinone
PubMed: 10453402
DOI: 10.1023/a:1006188301035 -
Pathogens and Disease Apr 2020Staphylococcus epidermidis is well known to be one of the major causes of infections related to medical devices, mostly due to its strong capacity to form...
Staphylococcus epidermidis is well known to be one of the major causes of infections related to medical devices, mostly due to its strong capacity to form device-associated biofilms. Nowadays, these infections represent a severe burden to the public health system and the necessity of novel antibacterial strategies for the treatment of these difficult-to-eradicate infections is urgent. The Antarctic marine bacterium Pseudoalteromonas haloplanktis TAC125 was found to be able to produce an anti-biofilm molecule, the pentadecanal, active against S. epidermidis. In this work, we modified one of the most widely used silicone-based polymers, polydimethylsiloxane (PDMS), by adsorption of pentadecanal and its most promising derivative, pentadecanoic acid, on the PDMS surface. The biofilm formation of S. epidermidis RP62A on both untreated and modified PDMS was performed in a parallel plate flow chamber system, demonstrating the capability of the proposed anti-biofilm coatings to strongly reduce the biofilm formation. Furthermore, drug-release capacity and long-term efficacy (21 days) were also proven for the pentadecanoic acid coating.
Topics: Aldehydes; Anti-Bacterial Agents; Biofilms; Coated Materials, Biocompatible; Dimethylpolysiloxanes; Equipment and Supplies; Fatty Acids; Staphylococcus epidermidis
PubMed: 32105313
DOI: 10.1093/femspd/ftaa012 -
PloS One 2022A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet...
Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems.
A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson's scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson's scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson's scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid.
Topics: Anti-Inflammatory Agents; Biomarkers; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Essential; Fatty Acids, Omega-3; Humans
PubMed: 35617322
DOI: 10.1371/journal.pone.0268778 -
Journal of Pediatric Gastroenterology... Apr 2021We sought to evaluate the relevance of pediatric dairy fat recommendations for children at risk for nonalcoholic fatty liver disease (NAFLD) by studying the association... (Observational Study)
Observational Study
OBJECTIVES
We sought to evaluate the relevance of pediatric dairy fat recommendations for children at risk for nonalcoholic fatty liver disease (NAFLD) by studying the association between dairy fat intake and the amount of liver fat. The effects of dairy fat may be mediated by odd chain fatty acids (OCFA), such as pentadecanoic acid (C15:0), and monomethyl branched chain fatty acids (BCFA), such as iso-heptadecanoic acid (iso-C17:0). Therefore, we also evaluated the association between plasma levels of OCFA and BCFA with the amount of liver fat.
METHODS
Observational, cross-sectional, community-based sample of 237 children ages 8 to 17. Dairy fat intake was assessed by 3 24-hour dietary recalls. Plasma fatty acids were measured by gas chromatography-mass spectrometry. Main outcome was hepatic steatosis measured by whole liver magnetic resonance imaging proton density fat fraction (MRI-PDFF).
RESULTS
Median dairy fat intake was 10.6 grams/day (range 0.0--44.5 g/day). Median liver MRI-PDFF was 4.5% (range 0.9%-45.1%). Dairy fat intake was inversely correlated with liver MRI-PDFF (r = -0.162; P = .012). In multivariable log linear regression, plasma C15:0 and iso-C17:0 were inverse predictors of liver MRI-PDFF (B = -0.247, P = 0.048; and B = -0.234, P = 0.009).
CONCLUSIONS
Dairy fat intake, plasma C15:0, and plasma iso-C17:0 were inversely correlated with hepatic steatosis in children. These hypothesis-generating findings should be tested through clinical trials to better inform dietary guidelines.
Topics: Adolescent; Child; Cross-Sectional Studies; Fatty Acids; Humans; Liver; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease
PubMed: 33399331
DOI: 10.1097/MPG.0000000000003040 -
Annals of Nuclear Medicine Nov 2022This study aimed to optimize various methods of calculating washout rates (WRs) of I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose...
OBJECTIVE
This study aimed to optimize various methods of calculating washout rates (WRs) of I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose triglyceride deposit cardiomyovasculopathy (TGCV) which is a rare disease entity identified in Japan and has been encoded in Orphanet (ORPHA code 565612).
METHODS
We calculated WRs of I-BMIPP from early (20 min) and delayed (200 min) images. We evaluated six methods of calculating WRs to discriminate TGVC patients (age, 56.8 ± 14.6 y; male, n = 13; female, n = 4) and 21 I-BMIPP studies were involved including 4 follow-up studies. Washout rates were calculated by two planar methods using anterior images with cardiac and background regions of interest (ROIs) and by four SPECT methods using either array and polar plots or summed short-axis images. The final diagnoses of TGCV were confirmed according to the 2020 diagnostic criteria, and the diagnostic accuracy of WRs calculated using the six methods was analyzed using the area under receiver-operating characteristics curves (ROC-AUC). Multiple scatter-plot matrix methods were evaluated with correlations for comparison.
RESULTS
All six methods were useful for diagnosis and did not significantly differ. The four SPECT methods showed excellent diagnostic accuracy (AUC 1.0), whereas the planar methods with and without background correction could be acceptable (AUC 0.857 and 0.964, respectively). The WRs were relatively lower for patients with CAD and remarkable metabolic defects than for patients with TGCV but without defects.
CONCLUSIONS
For the diagnosis of TGCV, the WR cutoff of 10% of I-BMIPP functioned well in planar and SPECT discrimination based on computational methods as a classifier. However, calculation optimization should improve TGCV diagnoses.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Triglycerides; Iodobenzenes; Fatty Acids; Tomography, Emission-Computed, Single-Photon; Myocardium
PubMed: 36155888
DOI: 10.1007/s12149-022-01787-9 -
The Journal of Biological Chemistry Jun 1951
Topics: Biological Transport; Fatty Acids; Lymphatic Vessels
PubMed: 14841191
DOI: No ID Found -
The American Journal of Clinical... May 2008
Topics: Animals; Biomarkers; Dairy Products; Dietary Fats; Fatty Acids; Humans; Milk; Myocardial Ischemia; Risk Factors
PubMed: 18469284
DOI: 10.1093/ajcn/87.5.1540