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International Journal of Molecular... Sep 2022Estrogen receptors are indicators of breast cancer adaptability to endocrine therapies, such as tamoxifen. Deficiency or absence of estrogen receptor α (ER-α) in...
Estrogen receptors are indicators of breast cancer adaptability to endocrine therapies, such as tamoxifen. Deficiency or absence of estrogen receptor α (ER-α) in breast cancer cells results in reduced efficacy of endocrine therapy. Here, we investigated the effect of combined tamoxifen and pentadecanoic acid therapy on ER-α-under-expressing breast cancer cells. Drug resistance gene expression patterns were determined by RNA sequencing analysis and in vitro experiments. For the first time, we demonstrate that the combined treatment of pentadecanoic acid, an odd-chain fatty acid, and tamoxifen synergistically suppresses the growth of human breast carcinoma MCF-7 stem cells (MCF-7/SCs), which were found to be tamoxifen-resistant and showed reduced ER-α expression compared with the parental MCF-7 cells. In addition, the combined treatment synergistically induced apoptosis and accumulation of sub-G1 cells and suppressed epithelial-to-mesenchymal transition (EMT). Exposure to this combination induces re-expression of ER-α at the transcriptional and protein levels, along with suppression of critical survival signal pathways, such as ERK1/2, MAPK, EGFR, and mTOR. Collectively, decreased ER-α expression was restored by pentadecanoic acid treatment, resulting in reversal of tamoxifen resistance. Overall, pentadecanoic acid exhibits the potential to enhance the efficacy of endocrine therapy in the treatment of ER-α-under-expressing breast cancer cells.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cell Line, Tumor; Drug Resistance, Neoplasm; ErbB Receptors; Estrogen Receptor alpha; Fatty Acids; Female; Humans; MCF-7 Cells; Receptors, Estrogen; TOR Serine-Threonine Kinases; Tamoxifen
PubMed: 36232636
DOI: 10.3390/ijms231911340 -
Marine Drugs Jan 2022Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds.... (Review)
Review
Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds. Some of the important North Bornean seaweed species are , , (Rhodophyta), , (Chlorophyta), and (Ochrophyta). This review aims to highlight the therapeutic potential of North Bornean seaweeds and their nutraceutical profiling. North Bornean seaweeds have demonstrated anti-inflammatory, antioxidant, antimicrobial, anticancer, cardiovascular protective, neuroprotective, renal protective and hepatic protective potentials. The protective roles of the seaweeds might be due to the presence of a wide variety of nutraceuticals, including phthalic anhydride, 3,4-ethylenedioxythiophene, 2-pentylthiophene, furoic acid (), eicosapentaenoic acid, palmitoleic acid, fucoxanthin, β-carotene (), eucalyptol, oleic acid, dodecanal, pentadecane (), canthaxanthin, oleic acid, pentadecanoic acid, eicosane (), pseudoephedrine, palmitic acid, monocaprin (), dictyohydroperoxide, squalene, fucosterol, saringosterol (), and lutein, neophytadiene, cholest-4-en-3-one and -vaccenic acid (). Extensive studies on the seaweed isolates are highly recommended to understand their bioactivity and mechanisms of action, while highlighting their commercialization potential.
Topics: Animals; Biological Products; Borneo; Dietary Supplements; Humans; Seaweed
PubMed: 35200631
DOI: 10.3390/md20020101 -
Genes & Nutrition Apr 2021Fermented foods are ubiquitous in human diets and often lauded for their sensory, nutritious, and health-promoting qualities. However, precise associations between the... (Review)
Review
BACKGROUND
Fermented foods are ubiquitous in human diets and often lauded for their sensory, nutritious, and health-promoting qualities. However, precise associations between the intake of fermented foods and health have not been well-established. This is in part due to the limitations of current dietary assessment tools that rely on subjective reporting, making them prone to memory-related errors and reporting bias. The identification of food intake biomarkers (FIBs) bypasses this challenge by providing an objective measure of intake. Despite numerous studies reporting on FIBs for various types of fermented foods and drinks, unique biomarkers associated with the fermentation process ("fermentation-dependent" biomarkers) have not been well documented. We therefore conducted a comprehensive, systematic review of the literature to identify biomarkers of fermented foods commonly consumed in diets across the world.
RESULTS
After title, abstract, and full-text screening, extraction of data from 301 articles resulted in an extensive list of compounds that were detected in human biofluids following the consumption of various fermented foods, with the majority of articles focusing on coffee (69), wine (69 articles), cocoa (62), beer (34), and bread (29). The identified compounds from all included papers were consolidated and sorted into FIBs proposed for a specific food, for a food group, or for the fermentation process. Alongside food-specific markers (e.g., trigonelline for coffee), and food-group markers (e.g., pentadecanoic acid for dairy intake), several fermentation-dependent markers were revealed. These comprised compounds related to the fermentation process of a particular food, such as mannitol (wine), 2-ethylmalate (beer), methionine (sourdough bread, cheese), theabrownins (tea), and gallic acid (tea, wine), while others were indicative of more general fermentation processes (e.g., ethanol from alcoholic fermentation, 3-phenyllactic acid from lactic fermentation).
CONCLUSIONS
Fermented foods comprise a heterogeneous group of foods. While many of the candidate FIBs identified were found to be non-specific, greater specificity may be observed when considering a combination of compounds identified for individual fermented foods, food groups, and from fermentation processes. Future studies that focus on how fermentation impacts the composition and nutritional quality of food substrates could help to identify novel biomarkers of fermented food intake.
PubMed: 33882831
DOI: 10.1186/s12263-021-00686-4 -
Nutrients Jun 2020Saturated fatty acids possess few health benefits compared to unsaturated fatty acids. However, increasing experimental evidence demonstrates the nutritionally...
Saturated fatty acids possess few health benefits compared to unsaturated fatty acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated fatty acids in human health. In this study, the anti-cancer effects of pentadecanoic acid were evaluated in human breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem cell properties compared to the parental MCF-7 cells. Pentadecanoic acid exerted selective cytotoxic effects in MCF-7/SC compared to in the parental cells. Moreover, pentadecanoic acid reduced the stemness of MCF-7/SC and suppressed the migratory and invasive ability of MCF-7/SC as evidenced by the results of flow cytometry, a mammosphere formation assay, an aldehyde dehydrogenase activity assay, and Western blot experiments conducted to analyze the expression of cancer stem cell markers-CD44, β-catenin, MDR1, and MRP1-and epithelial-mesenchymal transition (EMT) markers-snail, slug, MMP9, and MMP2. In addition, pentadecanoic acid suppressed interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cell cycle arrest at the sub-G1 phase, and promoted caspase-dependent apoptosis in MCF-7/SC. These findings indicate that pentadecanoic acid can serve as a novel JAK2/STAT3 signaling inhibitor in breast cancer cells and suggest the beneficial effects of pentadecanoic acid-rich food intake during breast cancer treatments.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Breast Neoplasms; Cell Transformation, Neoplastic; Epithelial-Mesenchymal Transition; Fatty Acids; Humans; Hyaluronan Receptors; Janus Kinase 2; MCF-7 Cells; Matrix Metalloproteinase 9; STAT3 Transcription Factor; Signal Transduction; Snail Family Transcription Factors; beta Catenin
PubMed: 32503225
DOI: 10.3390/nu12061663 -
Molecules (Basel, Switzerland) Jul 2022is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of (MEC) whole plant and an -butanol...
is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of (MEC) whole plant and an -butanol fraction of (NBFC) were analyzed by gas chromatography-mass spectrometry (GC-MS) to detect the phytochemicals. MEC and NBFC were tested for in vitro anti acetylcholinesterase (AChE) potential. The effect of both samples on intestinal propulsive movement and spasmolytic activity in the gastrointestinal tract (GIT) was also studied. About twelve compounds in MEC and three compounds in NBFC were tentatively identified through GC-MS. Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid. Both NBFC and MEC samples were checked for acute toxicity and were found to be highly toxic in a dose-dependent manner, causing diarrhea and emesis at 1 g/kg concentration in pigeons, with the highest lethargy and mortality above 3 g/kg. Both the samples of revealed significant ( ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation. NBFC (81.18 ± 2.5%) and MEC (68.28 ± 2.4%) significantly increased charcoal meal intestinal transit compared to distal water (41.15 ± 4.3%). NBFC exhibited a significant relaxant effect (EC = 3.40 ± 0.20 mg/mL) in spontaneous rabbit jejunum as compared to MEC (EC = 4.34 ± 0.68 mg/kg). Similarly, the impact of NBFC on KCl-induced contraction was more significant than that of MEC (EC values of 7.22 ± 0.06 mg/mL and 7.47 ± 0.57 mg/mL, respectively). The present study scientifically validates the folk use of in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in .
Topics: Animals; Constipation; Diarrhea; Euphorbiaceae; Laxatives; Phytochemicals; Plant Extracts; Rabbits
PubMed: 35807565
DOI: 10.3390/molecules27134321 -
Frontiers in Endocrinology 2023Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower...
INTRODUCTION
Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.
METHOD
The current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
RESULTS
A total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant ( < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.
DISCUSSION
Based on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.
Topics: Humans; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus; Glutamine; Sarcopenia; Diabetes Complications; Metabolome
PubMed: 37033246
DOI: 10.3389/fendo.2023.1119782 -
Annals of Nuclear Cardiology 2020Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008.... (Review)
Review
Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008. Defective intracellular lipolysis causes triglyceride (TG) accumulation in the myocardium and coronary artery vascular smooth muscle cells, which results in severe heart failure and coronary artery disease with poor prognosis. A known cause of TGCV is a genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in the intracellular hydrolysis of TG. TGCV is classified into primary TGCV with ATGL mutations and idiopathic TGCV without ATGL mutations. Since its discovery, the Japan TGCV Study Group has attempted to elucidate its pathophysiology, develop diagnostic procedures, and specific treatment. Myocardial scintigraphy with iodine-123--methyl iodophenyl-pentadecanoic acid (I-BMIPP) is a unique imaging modality for evaluating myocardial lipolysis The washout rate of I-BMIPP is an essential indicator for the diagnosis of TGCV. Along with our efforts to provide awareness of and insights into this disease concept, we found that the cumulative number of clinically diagnosed patients has reached >200 and the cases are distributed throughout Japan. In addition, we successfully completed three investigator-initiated clinical trials of a potential therapeutic agent (CNT-01) for TGCV, which was assigned by the Ministry of Health, Labour, and Welfare, Japan, under the SAKIGAKE Designation System in June 2020. Here, we provide the Diagnostic Criteria 2020 for TGCV in order to further promote this "rare and intractable disease" project.
PubMed: 37123492
DOI: 10.17996/anc.20-00131 -
Molecules (Basel, Switzerland) Mar 2023The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two...
The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two endophytic fungal strains were isolated from roots and identified as MT597434.1 and KU324798.1. Secondary metabolites produced by and were extracted and tested for their antimicrobial activity. The highest activity was noticed against and treated with and secondary metabolites, respectively. crude extract was mainly composed of Pentadecanoic acid, 14-methyl-, methyl ester and 9-Octadecenoic acid ()-, methyl ester (26.66 and 18.01%, respectively), while crude extract's major components were 2,4-Decadienal, (,) and 9-Octadecenoic acid ()-, and methyl ester (10.69 and 10.32%, respectively). Moreover, a comparative study between the fungal extracts and dicationic pyridinium iodide showed that the combination of and secondary metabolites with dicationic pyridinium iodide compound showed a synergistic effect against . The combined formulae inhibited the bacterial growth after 4 to 6 h through cell wall breakage and cells deformation, with intracellular components leakage and increased ROS production.
Topics: Iodides; Escherichia coli; Oleic Acid; Aspergillus niger; Complex Mixtures
PubMed: 36985405
DOI: 10.3390/molecules28062434 -
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 -
Research in Microbiology 2021The ability to form biofilms is a common feature of microorganisms, which can colonize a variety of surfaces, such as host tissues and medical devices, resulting in...
The ability to form biofilms is a common feature of microorganisms, which can colonize a variety of surfaces, such as host tissues and medical devices, resulting in infections highly resistant to conventional drugs. This aspect is particularly critical in polymicrobial biofilms involving both fungi and bacteria, therefore, to eradicate such severe infections, new and effective anti-biofilm strategies are needed. The efficacy of pentadecanal and pentadecanoic acid as anti-biofilm agents has been recently reported against different bacterial strains. Their chemical similarity with diffusible signal factors (DSFs), plus the already known ability of fatty acids to act as anti-biofilm agents, suggested to explore their use against Candida albicans and Klebsiella pneumoniae mixed biofilm. In this work, we demonstrated the ability of both molecules to prevent the formation and destabilize the structure of the dual-species biofilm. Moreover, the pentadecanoic acid anti-biofilm coating, previously developed through the adsorption of the fatty acid on polydimethylsiloxane (PDMS), was proved to prevent the polymicrobial biofilm formation in dynamic conditions by confocal laser scanning microscopy analysis. Finally, the evaluation of the expression levels of some biofilm-related genes of C. albicans and K. pneumoniae treated with pentadecanoic acid provided some insights into the molecular mechanisms underpinning its anti-biofilm effect.
Topics: Aldehydes; Anti-Bacterial Agents; Biofilms; Candida albicans; Dimethylpolysiloxanes; Fatty Acids; Gene Expression; Genes, Bacterial; Genes, Fungal; Klebsiella pneumoniae; Microbial Sensitivity Tests
PubMed: 34563667
DOI: 10.1016/j.resmic.2021.103880