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Nature Communications Dec 2023Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic...
Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.
Topics: Male; Mice; Animals; Catalase; Linoleic Acids; Linoleic Acid; Fatty Liver; Liver
PubMed: 38071367
DOI: 10.1038/s41467-023-44026-z -
Cancer Cell International Nov 2023"Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to... (Review)
Review
BACKGROUND AND AIM
"Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to colorectal cancer (CRC). In this manuscript, we discussed the epigenetic and metabolic change to present a extensive view of IBDs transition to CRC. This study discusses the possible biomarkers for evaluating the condition of IBDs patients, especially before the transition to CRC.
RESEARCH APPROACH
We searched "PubMed" and "Google Scholar" using the keywords from 2000 to 2022.
DISCUSSION
In this manuscript, interesting titles associated with IBD and CRC are discussed to present a broad view regarding the epigenetic and metabolic reprogramming and the biomarkers.
CONCLUSION
Epigenetics can be the main reason in IBD transition to CRC, and Hypermethylation of several genes, such as VIM, OSM4, SEPT9, GATA4 and GATA5, NDRG4, BMP3, ITGA4 and plus hypomethylation of LINE1 can be used in IBD and CRC management. Epigenetic, metabolisms and microbiome-derived biomarkers, such as Linoleic acid and 12 hydroxy 8,10-octadecadienoic acid, Serum M2-pyruvate kinase and Six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK and ADCY5) expression are valuable biomarkers for early detection and transition to CRC condition. Some miRs, such as miR-31, miR-139-5p, miR -155, miR-17, miR-223, miR-370-3p, miR-31, miR -106a, miR -135b and miR-320 can be used as biomarkers to estimate IBD transition to CRC condition.
PubMed: 37936149
DOI: 10.1186/s12935-023-03117-z -
Frontiers in Nutrition 2023Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the...
OBJECTIVE
Diets high in glucose or fat contribute to an increased prevalence of the diseases. Therefore, the objective of the current research was to observe and evaluate the impact of dietary components on different metabolomic profiles in primary tissues of mice.
METHODS
For 8 weeks, diet with high-glucose or-fat was given to C57BL/6 J mice. The levels of metabolites in the primary tissues of mice were studied using gas chromatography-mass spectrometry (GC-MS) and analyzed using multivariate statistics.
RESULTS
By comparing the metabolic profiles between the two diet groups and control group in mice main tissues, our study revealed 32 metabolites in the high-glucose diet (HGD) group and 28 metabolites in the high-fat diet (HFD) group. The most significantly altered metabolites were amino acids (AAs; L-alanine, L-valine, glycine, L-aspartic acid, L-isoleucine, L-leucine, L-threonine, L-glutamic acid, phenylalanine, tyrosine, serine, proline, and lysine), fatty acids (FAs; propanoic acid, 9,12-octadecadienoic acid, pentadecanoic acid, hexanoic acid, and myristic acid), and organic compounds (succinic acid, malic acid, citric acid, L-(+)-lactic acid, myo-inositol, and urea). These metabolites are implicated in many metabolic pathways related to energy, AAs, and lipids metabolism.
CONCLUSION
We systematically analyzed the metabolic changes underlying high-glucose or high-fat diet. The two divergent diets induced patent changes in AA and lipid metabolism in the main tissues, and helped identify metabolic pathways in a mouse model.
PubMed: 37492592
DOI: 10.3389/fnut.2023.1171806 -
Scientific Reports Nov 2023Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan,...
Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25-50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.
Topics: Humans; Female; Uterine Cervical Neoplasms; Papillomavirus Infections; Cell Cycle Checkpoints; Cyclin-Dependent Kinases; HeLa Cells; Apoptosis; Oncogene Proteins; Human papillomavirus 16; Cell Proliferation; Oncogene Proteins, Viral; Tumor Suppressor Protein p53
PubMed: 37932321
DOI: 10.1038/s41598-023-44365-3 -
BMC Endocrine Disorders Aug 2023This study was to explore the association between dietary polyunsaturated fatty acids (PUFAs) consumption and cardiovascular diseases (CVDs), all-cause mortality, and...
BACKGROUND
This study was to explore the association between dietary polyunsaturated fatty acids (PUFAs) consumption and cardiovascular diseases (CVDs), all-cause mortality, and CVD-specific mortality.
METHODS
This retrospective cohort study extracted demographic and clinical data of 38,838 adult participants from the National Health and Nutrition Examination Survey (NHANES) database in 2003-2018. We explored the association between octadecadienoic acid (ODA), octadecatrienoic acid (ALA), octadecatetraenoic acid (ODTA), eicosatetraenoic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) and different CVDs using weighted univariate and multivariate logistic regression analyses with odds ratio (OR) and 95% confidence interval (CI). The PUFAs were divided into four levels according to the quartiles (≤ Q1, Q1 to Q2, Q1 to Q2, > Q3). Weighted univariate and multivariate COX regression analyses with hazard ratio (HR) and 95% CI were used for exploring the association between PUFAs and all-cause mortality, CVD-specific mortality and other cause-specific mortality.
RESULTS
During the follow-up, a total of 4,908 (9.12%) eligible participants died. The results showed that after adjusting for covariates, ODTA intake was related to low odds of coronary heart disease (CHD) [OR = 0.75, 95%CI: (0.64-0.88)]. Q1-Q2 quartile of ALA [OR = 0.81, 95%CI: (0.66-0.99)] and Q2-Q3 quartile of DPA [OR = 0.78, 95%CI: (0.62-0.99)] intakes were linked to low odds of heart attack, and > Q3 quartile of ODA intake was associated with low odds of congestive heart failure (CHF) [OR = 0.66, 95%CI: (0.49-0.90)] and stroke [OR = 0.65, 95%CI: (0.47-0.90)]. Q2-Q3 quartile of DPA intake was linked to low odds of angina [OR = 0.76, 95%CI: (0.58-0.99)]. Higher ALA intake was associated with a lower risk of all-cause mortality [Q2-Q3: HR = 0.86, 95%CI: (0.74-0.99); > Q3: HR = 0.76, 95%CI: (0.63-0.91)]. Additionally, Q2-Q3 quartile of ALA, Q1-Q2 quartile of AA and DPA intakes were respectively related to a low risk of CVD-specific mortality, while that > Q3 quartile of ALA related to that of mortality by other causes.
CONCLUSION
Our study found that PUFAs were associated with different CVDs, and higher ALA intake was related to lower risk of all-cause mortality. Ensuring adequate intake of PUFAs was beneficial to the health and may decrease the risk of mortality.
Topics: Adult; Humans; Cardiovascular Diseases; Nutrition Surveys; Retrospective Studies; Fatty Acids, Unsaturated; Heart Failure
PubMed: 37644429
DOI: 10.1186/s12902-023-01412-4 -
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 -
BMC Genomics Oct 2023Background Puccinia arachidis fungus causes rust disease in the peanut plants (Arachis hypogaea L.), which leads to high yield loss. Metabolomic profiling of Arachis...
Background Puccinia arachidis fungus causes rust disease in the peanut plants (Arachis hypogaea L.), which leads to high yield loss. Metabolomic profiling of Arachis hypogaea was performed to identify the pathogen-induced production of metabolites involved in the defense mechanism of peanut plants. In this study, two peanut genotypes, one susceptible (JL-24) and one resistant (GPBD-4) were inoculated with Puccinia arachidis fungal pathogen. The metabolic response was assessed at the control stage (0 day without inoculation), 2 DAI (Day after inoculation), 4 DAI and 6 DAI by Gas Chromatography-Mass Spectrometry (GC-MS). Results About 61 metabolites were identified by NIST library, comprising sugars, phenols, fatty acids, carboxylic acids and sugar alcohols. Sugars and fatty acids were predominant in leaf extracts compared to other metabolites. Concentration of different metabolites such as salicylic acid, mannitol, flavonoid, 9,12-octadecadienoic acid, linolenic acid and glucopyranoside were higher in resistant genotype than in susceptible genotype during infection. Systemic acquired resistance (SAR) and hypersensitive reaction (HR) components such as oxalic acid was elevated in resistant genotype during pathogen infection. Partial least square-discriminant analysis (PLS-DA) was applied to GC-MS data for revealing metabolites profile between resistant and susceptible genotype during infection. Conclusion The phenol content and oxidative enzyme activity i.e. catalase, peroxidase and polyphenol oxidase were found to be very high at 4 DAI in resistant genotype (p-value < 0.01). This metabolic approach provides information about bioactive plant metabolites and their application in crop protection and marker-assisted plant breeding.
Topics: Arachis; Plant Breeding; Metabolome; Fatty Acids; Sugars
PubMed: 37872498
DOI: 10.1186/s12864-023-09725-3 -
Antibiotics (Basel, Switzerland) Sep 2023L. Poaceae stigma (corn silk, CS) is a byproduct of agricultural waste and is used as a traditional herb in many countries. CS is rich in chemical compounds known to...
Antioxidant, Anti-Tyrosinase, and Anti-Skin Pathogenic Bacterial Activities and Phytochemical Compositions of Corn Silk Extracts, and Stability of Corn Silk Facial Cream Product.
L. Poaceae stigma (corn silk, CS) is a byproduct of agricultural waste and is used as a traditional herb in many countries. CS is rich in chemical compounds known to benefit human health and is also a remedy for infectious diseases and has anti-proliferative effects on human cancer cell lines. In the present study, CS extract has been evaluated for its antioxidant, antibacterial, and anti-tyrosinase activities and its phytochemical composition. The higher total phenolic and flavonoid contents were found in the ethanolic extract of corn silk (CSA), at 28.27 ± 0.86 mg gallic acid equivalent/g extract and 4.71 ± 0.79 mg quercetin equivalent/g extract, respectively. Moreover, the antioxidant content of CSA was found at 5.22 ± 0.87 and 13.20 ± 0.42 mg gallic acid equivalent/g extract using DPPH and reducing power assays. Furthermore, the ethanolic extract of corn silk showed tyrosinase inhibition with an IC value of 12.45 µg/mL. The bacterial growth inhibition of CSA was tested using agar disc diffusion and broth dilution assays against and . It was found that CSA inhibited and with an inhibition zone of 11.7 ± 1.2 and 9.3 ± 0.6 mm, respectively. Moreover, the CSA showed MIC/MBC of 15.625 mg/mL against . The following phytochemical compounds were detected in CSA: cardiac glycosides; -hexadecanoic acid; hexadecanoic acid, ethyl ester; oleic acid; and 9,12-octadecadienoic acid, ethyl ester. After the corn silk cream product was formulated, the product demonstrated stability without phase separation. This research is beneficial for promoting effective ways to use agricultural waste while utilizing the antioxidant, anti-tyrosinase, and antibacterial activities of corn silk. Moreover, the use of technology and innovation to obtain high-value CS extract will benefit the development of commercial cosmetic products by providing safe, natural, and quality ingredients to the consumer.
PubMed: 37760739
DOI: 10.3390/antibiotics12091443 -
Frontiers in Molecular Biosciences 2023one of the most destructive crop pathogens worldwide, causes bacterial wilt disease in a wide range of host plants. The major component of the outer membrane of...
one of the most destructive crop pathogens worldwide, causes bacterial wilt disease in a wide range of host plants. The major component of the outer membrane of Gram-negative bacteria, lipopolysaccharides (LPS), has been shown to function as elicitors of plant defense leading to the activation of signaling and defense pathways in several plant species. LPS from a strain virulent on tomato (LPS), were purified, chemically characterized, and structurally elucidated. The lipid A moiety consisted of tetra- to hexa-acylated -phosphorylated disaccharide backbone, also decorated by aminoarabinose residues in minor species, while the O-polysaccharide chain consisted of either linear tetrasaccharide or branched pentasaccharide repeating units containing α-L-rhamnose, -acetyl-β-D-glucosamine, and β-L-xylose. These properties might be associated with the evasion of host surveillance, aiding the establishment of the infection. Using untargeted metabolomics, the effect of LPS elicitation on the metabolome of leaves was investigated across three incubation time intervals with the application of UHPLC-MS for metabolic profiling. The results revealed the production of oxylipins, e.g., trihydroxy octadecenoic acid and trihydroxy octadecadienoic acid, as well as several hydroxycinnamic acid amide derivatives, e.g., coumaroyl tyramine and feruloyl tyramine, as phytochemicals that exhibit a positive correlation to LPS treatment. Although the chemical properties of these metabolite classes have been studied, the functional roles of these compounds have not been fully elucidated. Overall, the results suggest that the features of the LPS chemotype aid in limiting or attenuating the full deployment of small molecular host defenses and contribute to the understanding of the perturbation and reprogramming of host metabolism during biotic immune responses.
PubMed: 37635940
DOI: 10.3389/fmolb.2023.1232233 -
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