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Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism....
BACKGROUND
Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS.
MATERIALS AND METHODS
50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls.
RESULT
Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate.
CONCLUSION
Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.
Topics: Humans; Polycystic Ovary Syndrome; Female; Metabolomics; Adult; Young Adult; Case-Control Studies; Metabolome; Testosterone; Contraceptives, Oral; Contraceptives, Oral, Combined; Biomarkers
PubMed: 38948525
DOI: 10.3389/fendo.2024.1354214 -
Foods (Basel, Switzerland) Jun 2024Conjugated linoleic acid (CLA) is a class of naturally occurring octadecadienoic acid in humans and animals and is a general term for a group of conformational and...
Conjugated linoleic acid (CLA) is a class of naturally occurring octadecadienoic acid in humans and animals and is a general term for a group of conformational and positional isomers of linoleic acid. In order to obtain the development of excellent lactic acid strains with a high production of conjugated linoleic acid, 32 strains with a possible CLA conversion ability were obtained by initial screening using UV spectrophotometry, and then the strains were re-screened by gas chromatography, and finally, the strain with the highest CLA content was obtained. The strains were optimized for cultivation by changing the amount of substrate addition, inoculum amount, and fermentation time. The results showed that the yield of the experimentally optimized strain for the conversion of conjugated linoleic acid could reach 94.68 ± 3.57 μg/mL, which was 74.4% higher than the initial yield of 54.28 ± 2.12 μg/mL of the strain. The results of this study can provide some basis for the application of conjugated linoleic acid production by in the fermentation of lactic acid bacteria.
PubMed: 38928772
DOI: 10.3390/foods13121830 -
Frontiers in Cellular and Infection... 2024Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here...
Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: -10--15-octadecadienoic acid (t10,c15-18:2) and -9--15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.
Topics: Animals; Mice; Vascular Endothelial Growth Factor A; Fatty Acids, Omega-3; Down-Regulation; Disease Models, Animal; Dermatitis, Contact; Dinitrofluorobenzene; Skin; Keratinocytes; Female; Dermatitis, Allergic Contact; Humans; Gastrointestinal Microbiome; Feces
PubMed: 38841110
DOI: 10.3389/fcimb.2024.1355679 -
Frontiers in Immunology 2024Various gut bacteria, including , possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from...
The gut lactic acid bacteria metabolite, 10-oxo--6,-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling.
Various gut bacteria, including , possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo--6,-11-octadecadienoic acid (γKetoC), a γ-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with γKetoC significantly suppressed proliferation of CD4 T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c cells isolated from the spleen. γKetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of γKetoC on DCs. We also found that γKetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of γKetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and mice with colitis. In contrast, the pathology of colitis was deteriorated in mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in γKetoC-mediated anti-inflammatory responses.
Topics: Animals; NF-E2-Related Factor 2; Mice; Receptors, G-Protein-Coupled; Signal Transduction; Gastrointestinal Microbiome; Mice, Inbred C57BL; Inflammatory Bowel Diseases; Mice, Knockout; Cytokines; Disease Models, Animal; Dextran Sulfate; Oleic Acids; Lactobacillus plantarum; Colitis; Dendritic Cells; Male
PubMed: 38745644
DOI: 10.3389/fimmu.2024.1374425 -
Genes Mar 2024Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of...
Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of maize; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene leads to increased resistance of maize to herbivory by fall armyworms (FAWs). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of , referred to as . To test whether introgression of the locus into a herbivore-susceptible B73 background that contains a single gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either two, one, or zero copies of the locus in the B73 background via six backcrosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the locus in B73. The resulting B73-2× inbred line displayed increased resistance against FAW, associated with increased expression of , increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×, resulting from the increased JA catabolism. Furthermore, B73-2× displayed reduced water loss in response to drought stress, likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into productive but susceptible crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.
Topics: Zea mays; Animals; DNA Copy Number Variations; Plant Proteins; Lipoxygenase; Herbivory; Oxylipins; Plant Diseases
PubMed: 38674336
DOI: 10.3390/genes15040401 -
The Journal of Biological Chemistry May 2024Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise...
Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products exhibit a conjugated enone UV chromophore, a result that conflicts with the literature and is relevant to the mass spectral interpretation of 1,4 versus 1,6 thiol adduction. Aided by the development of an HPLC solvent system that separates the GSH diastereomers and thus avoids overlap of signals in proton NMR experiments, we established the two major conjugates are formed by 1,6 addition of GSH at the 9-carbon of 13-oxo-ODE with the remaining double bond α to the thiol in the 10,11 position. N-acetyl cysteine reacts similarly, while β-mercaptoethanol gives equal amounts of 1,4 and 1,6 addition products. Equine glutathione transferase catalyzed 1,6 addition of GSH to the two major diastereomers in 44:56 proportions. LC-MS in positive ion mode gives a product ion interpreted before as evidence of 1,4-thiol adduction, whereas here we find this ion using the authentic 1,6 adduct. LC-MS with negative ion APCI gave a fragment selective for 1,4 adduction. These results clarify the structures of thiol conjugates of a prototypical unsaturated keto-fatty acid and have relevance to the application of LC-MS for the structural analysis of keto-fatty acid glutathione conjugation.
Topics: Glutathione; Sulfhydryl Compounds; Mass Spectrometry; Chromatography, High Pressure Liquid; Chromatography, Liquid; Mercaptoethanol; Liquid Chromatography-Mass Spectrometry
PubMed: 38636660
DOI: 10.1016/j.jbc.2024.107293 -
Foods (Basel, Switzerland) Mar 2024The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by...
The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by gas chromatography-mass spectrometry. Thirty-one components were identified, with 3-acetoxy-7, 8-epoxylanostan-11-ol (38.16%), β-monoolein (14.4%), lycopene, 1,2-dihydro-1-hydroxy- (10.21%), and 9,12-octadecadienoic acid, 2-phenyl-1,3-dioxan-5-yl ester (9.21%) as main compounds. In addition, molecular docking was employed to identify potential protein targets for the 31 quantified essential oil components. Inhibition of these targets is typically associated with antibacterial or antioxidant properties. Molecular docking revealed that six of these components, namely, 13-heptadecyn-1-ol, ascabiol, geranylgeraniol, anethole, and quinol dimethyl ether, outperformed the native ligand (hypoxanthine) of xanthine oxidase in terms of theoretical binding affinity, therefore implying a significant in silico inhibitory potential against xanthine oxidase. These findings suggest that the essential oil extracted from flowers could be valuable for developing protein-targeted antioxidant compounds with applications in the food, pharmaceutical, and cosmetic industries.
PubMed: 38611313
DOI: 10.3390/foods13071007 -
World Journal of Experimental Medicine Mar 2024The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques...
BACKGROUND
The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy. (), a perennial herb belonging to the family is extensively used in conventional medication.
AIM
To determine the existence of therapeutic components in leaf and callus extracts from wild plants using gas chromatography-mass spectrometry (GC-MS).
METHODS
In this study, we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts. Various growth regulators such as 6-benzylaminopurine (BAP), 2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthylacetic acid (NAA), and di-phenylurea (DPU) were added to plant leaves and callus and grown on MS medium.
RESULTS
The results clearly indicated that the addition of BAP (2.0 mg/L), 2,4-D (0.2 mg/mL), DPU (2.0 mg/L) and 2,4-D (0.2 mg/mL) in MS medium resulted in rapid callus development. The plant profile of extracts by GC-MS analysis showed that 24, 10, and 14 bioactive constituents were detected in the methanolic extract of leaf, green callus and the methanolic extract of white loose callus, respectively.
CONCLUSION
Octadecadienoic acid, hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract. Octadecadienoic acid was the most common constituent in all samples. The maximum concentration of octadecadienoic acid in leaves, green callus and white loose callus was 21.93%, 47.79% and 40.38%, respectively. These findings demonstrate that the concentration of octadecadienoic acid doubles compared to . In addition to octadecadienoic acid; butyric acid, benzene, 1-methoxy-4-(1-propenyl), dospan, tridecanedialdehyde, methylcyclohexenylbutanol, chlorpyrifos, n-secondary terpene diester, anflunine and other important active compounds were also detected. All these components were only available in callus formed . This study showed that the callus contained additional botanical characteristics compared with wild plants. Due to the presence of numerous bioactive compounds, the medical use of for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.
PubMed: 38590309
DOI: 10.5493/wjem.v14.i1.88064 -
ACS Omega Apr 2024This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the...
This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (,), methyl ester, and others. The addition of methanolic extract to an AgNO solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.
PubMed: 38585127
DOI: 10.1021/acsomega.3c10119 -
Frontiers in Cellular and Infection... 2024Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune...
BACKGROUND
Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.
METHODS
We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4 ≥500 cells/mm, and CD4/CD8 ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).
RESULTS
PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.
CONCLUSION
PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.
Topics: Humans; Cross-Sectional Studies; Metabolomics; Biomarkers; Inflammation; HIV Infections
PubMed: 38550617
DOI: 10.3389/fcimb.2024.1340610