PubMed

Planta. 2024 Dec 10;261(1):10. doi: 10.1007/s00425-024-04587-9.ABSTRACTBrassica vegetables are one of the possible solutions to tackle the emerging human diseases and malnutrition due to their rich content of phyto-nutraceutaical compounds. The genomics enabled tools have facilitated the elucidation of molecular regulation, mapping of genes/QTLs governing nutraceutical compounds, and development of nutrient-rich Brassica vegetables. The enriched food products or foods as whole termed as functional foods are intended to provide health benefits. The 2500 year old Hippocratic phrase 'let thy food be thy medicine and thy medicine be thy food' remained in anonymity due to lack of sufficient evidence. However, today, we are facing reappraisal of healthy nutritious functional foods in battling diseases. In this context, the Brassica vegetables represent the most extensively investigated class of functional foods. An optimal consumption of Brassica vegetables is associated with lowering the risks of several types of cancer, chronic diseases, cardiovascular disease, and help in autism. In the post-genomic era, the integration of genetic and neoteric omics tools like transcriptomics, metabolomics, and proteomics have illuminated the downstream genetic mechanisms governing functional food value of Brassica vegetables. In this review, we have summarized in brief the phyto-nutraceutical profile and their functionality in Brassica vegetables. This review also highlights the progress made in identification of candidate genes/QTLs for accumulation of bioactive compounds in Brassica vegetables. We summarize the molecular regulation of major phytochemicals and breeding triumphs in delivering multifunctional Brassica vegetables.PMID:39656314 | DOI:10.1007/s00425-024-04587-9

Microbiol Spectr. 2024 Dec 10:e0099624. doi: 10.1128/spectrum.00996-24. Online ahead of print.ABSTRACTThe Amazon, an important biodiversity hotspot, remains poorly explored in terms of its microbial diversity and biotechnological potential. The present study characterized the metabolic potential of Gram-positive strains of the Actinomycetes and Bacilli classes isolated from soil samples of an Amazon Conservation Unit. The sequencing of the 16S rRNA gene classified the strains ACT015, ACT016, and FIR094 within the genera Streptomyces, Rhodococcus, and Brevibacillus, respectively. Genome mining identified 33, 17, and 14 biosynthetic gene clusters (BGCs) in these strains, including pathways for the biosynthesis of antibiotic and antitumor agents. Additionally, 40 BGCs (62,5% of the total BGCs) were related to unknown metabolites. The OSMAC approach and untargeted metabolomics analysis revealed a plethora of metabolites under laboratory conditions, underscoring the untapped chemical diversity and biotechnological potential of these isolates. Our findings illustrated the efficacy of the metabologenomics approach in elucidating secondary metabolism and selecting BGCs with chemical novelty.IMPORTANCEThe largest rainforest in the world is globally recognized for its biodiversity. However, until now, few studies have been conducted to prospect natural products from the Amazon microbiome. In this work, we isolated three free-living bacterial species from the microbiome of pristine soils and used two high-throughput technologies to reveal the vast unexplored repertoire of secondary metabolites produced by these microorganisms.PMID:39656018 | DOI:10.1128/spectrum.00996-24

J Am Heart Assoc. 2024 Dec 10:e036906. doi: 10.1161/JAHA.124.036906. Online ahead of print.ABSTRACTBACKGROUND: Contemporary risk assessment in patients with coronary atherosclerotic disease (CAD) often relies on invasive angiography. However, we aimed to explore the potential of metabolomic biomarkers in reflecting residual risk in patients with CAD after moderate lipid-lowering therapy.METHODS AND RESULTS: We analyzed serum metabolomic profile among 2560 patients with newly diagnosed CAD undergoing moderate lipid-lowering therapy, through nuclear magnetic resonance spectroscopy and quantified 175 metabolites, predominantly lipoproteins and their components. CAD severity was evaluated using Gensini score for plaque burden and circulating cardiac troponin T levels for plaque instability. The association of metabolites with CAD severity was examined using multivariate linear regression, and the underlying potential causality was explored using a 2-sample Mendelian randomization approach. Two composite metabolomic indices were constructed to reflect CAD severity using least absolute shrinkage and selection operator linear regression, and their associations with risk of major adverse cardiac events during a median follow-up of 3.8 years were evaluated using Cox models. Our investigation revealed that triglycerides and apolipoprotein B in low-density lipoprotein particles displayed stronger associations with CAD severity compared with the clinically used low-density lipoprotein cholesterol marker. In large high-density lipoprotein, components like cholesterol, cholesterol esters, triglyceride, apolipoprotein A1/A2 showed inverse associations with CAD severity. Certain metabolites, including apolipoprotein B and dihydrothymine, showed a putative causal link with Gensini score. Notably, per standard deviation increase in Gensini score-based metabolomic index was associated with 14.8% higher major adverse cardiac event risk (hazard ratio, 1.148 [95% CI, 1.018-1.295]) independent of demographic factors, medication use, and disease status.CONCLUSIONS: Our findings highlight the potential of nuclear magnetic resonance-based metabolomics in identifying novel biomarkers of plaque burden and instability. Metabolites related to plaque burden may facilitate noninvasive assessment of CAD prognosis.PMID:39655754 | DOI:10.1161/JAHA.124.036906

J Proteome Res. 2024 Dec 10. doi: 10.1021/acs.jproteome.4c00747. Online ahead of print.ABSTRACTPeg-IFNα is one of the current therapeutic strategies for Hepatitis B virus (HBV) seroclearance. Nevertheless, the underlying mechanisms are not yet adequately understood. The objective of this study was to explore the potential mechanisms using multiomics approach. For the first time, we revealed the transcriptomic, proteomic, and metabolomic characterizations of Peg-IFNα-induced HBsAg seroclearance. We found that Peg-IFNα caused significant changes during the treatment. Patients who achieved HBsAg seroclearance were characterized as having decreased transcriptional activity of genes involved in fatty acid metabolism and the glycolysis/gluconeogenesis pathway, with up-regulated expression of fatty acid degradation-related proteins. Consistently, mitochondrial TCA cycle metabolites, including citric, isocitric, and malic acids, were significantly elevated in patients who achieved HBsAg seroclearance. We also observed up-regulated transcriptional activity of NK cell-mediated cytotoxicity, positive regulation of B cell activation, immunoglobulin production, and T cell receptor complex in functional-cured patients. Conversely, the metabolites associated with unsaturated fatty acid biosynthesis were increased in HBsAg persistent patients, and the transcriptional activity of immunoglobulin production and T cell receptor complex was down-regulated after 48 weeks of Peg-IFNα treatment. Our findings provided valuable resources to better understand the process of HBsAg seroclearance and shed new light on the pathways to facilitate higher functional cure rates for CHB.PMID:39655723 | DOI:10.1021/acs.jproteome.4c00747

FASEB J. 2024 Dec 15;38(23):e70240. doi: 10.1096/fj.202401771R.ABSTRACTThe nutritional contents of breastmilk (BM) directly participate in neonatal metabolism via breastfeeding. Currently, there is limited research on BM metabolites and proteins compositions, and their alterations during the long lactation period in Hong Kong mothers. In this study, liquid chromatography-mass spectrometry-based metabolomics, lipidomics and proteomics studies were applied to compare the compositions in BM of Hong Kong lactating mothers at the 2nd, 6th, and 12th months after delivery. Distinct metabolomics and lipidomics signatures in 6th month versus 2nd month and 12th month versus 2nd month were observed, and a total of 19 differential metabolites and 105 lipids were identified. Metabolomics study showed the significant alterations in key pathways involved in biotin metabolism, amino acid, and fatty acid-associated metabolisms. Lipidomics analysis indicated the accumulation of triglyceride and ceramide during the lactation period. The remodeling of glycerophospholipids was also observed during 12-month period. Moreover, 28 differentially expressed proteins were identified and mainly associated with GO functions and KEGG pathways of ribosome and complement and coagulation cascades, which were validated by network analysis. Our research contributes to the understanding of the BM compositions and differences during the long lactation period in postpartum women of Hong Kong.PMID:39655667 | DOI:10.1096/fj.202401771R

Antioxid Redox Signal. 2024 Dec 10. doi: 10.1089/ars.2024.0557. Online ahead of print.ABSTRACTAims: Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status. Mitochondrial transmembrane potential, superoxide production, and mass were measured by flow cytometry in fresh platelets. Metabolomics analysis was performed on plasma samples. Global arginine bioavailability was calculated as the ratio of arginine/(ornithine+citrulline). Results: Global arginine bioavailability is consistently lower than controls in all PH groups. Although the mitochondrial mass is similar across all PH groups and controls, superoxide production and transmembrane potential vary across groups. Mitochondrial superoxide is higher in group 1 PAH and lowest in group 3 compared with other groups, while transmembrane potential is lower in group 1 PAH than controls or group 3. The alterations in mitochondrial functions of group 1 PAH are associated with changes in fatty acid metabolism. Mitochondrial transmembrane potential in group 1 PAH is associated with transplant-free survival. Conclusion: While alterations in mitochondrial function are found in all PH groups, group 1 PAH has a unique mitochondrial phenotype with greater superoxide and lower transmembrane potential linked to fatty acid metabolism, and clinically to survival. Antioxid. Redox Signal. 00, 000-000.PMID:39655485 | DOI:10.1089/ars.2024.0557

Eur J Immunol. 2024 Dec 10:e202451129. doi: 10.1002/eji.202451129. Online ahead of print.ABSTRACTThe development of an effective antitumor response relies on the synergistic actions of various immune cells that recognize tumor cells via distinct receptors. Tumors, however, often manipulate receptor-ligand interactions to evade recognition by the immune system. Recently, we highlighted the role of neolacto-series glycosphingolipids (nsGSLs), produced by the enzyme β1,3-N-acetylglucosaminyltransferase 5 (B3GNT5), in tumor immune escape. We previously demonstrated that loss of signal peptide peptidase like 3 (SPPL3), an inhibitor of B3GNT5, results in elevated levels of nsGSLs and impairs CD8 T cell activation. The impact of loss of SPPL3 and an elevated nsGSL profile in tumor cells on innate immune recognition remains to be elucidated. This study investigates the antitumor efficacy of neutrophils, NK cells, and γδ T cells on tumor cells lacking SPPL3. Our findings demonstrate that SPPL3-deficient target cells are less susceptible to trogocytosis by neutrophils and killing by NK cells and γδ T cells. Mechanistically, SPPL3 influences trogocytosis and γδ T cell-instigated killing through modulation of nsGSL expression, whereas SPPL3-mediated reduced killing by NK cells is nsGSL-independent. The nsGSL-dependent SPPL3 sensitivity depends on the proximity of surface receptor domains to the cell membrane and the affinity of receptor-ligand interactions as shown with various sets of defined antibodies. Thus, SPPL3 expression by tumor cells alters crosstalk with immune cells through the receptor-ligand interactome thereby driving escape not only from adaptive but also from innate immunity. These data underline the importance of investigating a potential synergism of GSL synthesis inhibitors with current immune cell-activating immunotherapies.PMID:39655358 | DOI:10.1002/eji.202451129

Lancet Reg Health Am. 2024 Nov 25;40:100952. doi: 10.1016/j.lana.2024.100952. eCollection 2024 Dec.ABSTRACTBACKGROUND: Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America.METHODS: This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at five referral centres across Latin America. Demographic, biochemical, and clinical data were analysed.FINDINGS: A total of 309 patients were enrolled, demonstrating a balanced distribution of CCA subtypes (intrahepatic, perihilar, and distal), with Hispanics and Caucasians as the predominant ethnic groups, followed by Africans. Major risk factors identified included age, diabetes, obesity, MASLD, bile duct stones, and cholecystitis. Disparities in overweight/obesity prevalence were noted among CCA subtypes and ethnicities, with higher rates in extrahepatic CCA and among Hispanics and Caucasians. At diagnosis, 72% of patients had ECOG-PS scores of 0-1, with disease presentations ranging from localized (47%) to locally advanced (19%) and metastatic (34%). Patients who did not receive any anti-cancer therapy exhibited a median survival of 2.3 months. Survival rates significantly improved across treatment modalities, with surgery yielding the longest (34 months), followed by chemotherapy (8 months). Notably, Africans presented with worse ECOG-PS scores and more advanced disease, while Hispanics were less frequently treated with chemotherapy for advanced disease, contributing to lower survival rates (8.3 and 6 months, respectively) compared to Caucasians (12.6 months).INTERPRETATION: The high prevalence of late-stage CCA diagnosis in Latin America, particularly among individuals of African ethnicity, coupled with a significant proportion of Hispanic patients not receiving chemotherapy, underscores the dismal prognosis for these patients. These findings reveal structural challenges in cancer screening and healthcare access among diverse ethnic backgrounds and lower socioeconomic statuses in the region. Urgent measures are needed, including the identification of preventable risk factors, raising awareness among high-risk populations, and establishing equitable health coverage to address these disparities.FUNDING: European Union's Horizon 2020 R&I Program, Incyte Bioscience International Sàrl, and European Association for the Study of the Liver (EASL).PMID:39655285 | PMC:PMC11626722 | DOI:10.1016/j.lana.2024.100952

Front Genet. 2024 Nov 20;15:1489694. doi: 10.3389/fgene.2024.1489694. eCollection 2024.ABSTRACTSparse canonical correlation analysis (sCCA) has been a useful approach for integrating different high-dimensional datasets by finding a subset of correlated features that explain the most correlation in the data. In the context of microbiome studies, investigators are always interested in knowing how the microbiome interacts with the host at different molecular levels such as genome, methylol, transcriptome, metabolome and proteome. sCCA provides a simple approach for exploiting the correlation structure among multiple omics data and finding a set of correlated omics features, which could contribute to understanding the host-microbiome interaction. However, existing sCCA methods do not address compositionality, and its application to microbiome data is thus not optimal. This paper proposes a new sCCA framework for integrating microbiome data with other high-dimensional omics data, accounting for the compositional nature of microbiome sequencing data. It also allows integrating prior structure information such as the grouping structure among bacterial taxa by imposing a "soft" constraint on the coefficients through varying penalization strength. As a result, the method provides significant improvement when the structure is informative while maintaining robustness against a misspecified structure. Through extensive simulation studies and real data analysis, we demonstrate the superiority of the proposed framework over the state-of-the-art approaches.PMID:39655222 | PMC:PMC11626081 | DOI:10.3389/fgene.2024.1489694

Front Immunol. 2024 Nov 25;15:1429010. doi: 10.3389/fimmu.2024.1429010. eCollection 2024.ABSTRACTINTRODUCTION: Dermatomyositis (DM) is an idiopathic inflammatory myopathy. Because of clinical heterogeneity, the metabolite profile of DM patients with different myositis-specific autoantibodies (MSAs) remains elusive. This study aimed to explore the metabolomics characteristics of the serum in DM with different MSAs, low or high disease activity, and interstitial lung disease.METHODS: Untargeted metabolomics profiling was performed in the serum of a discovery cohort (n=96) and a validation cohort (n=40), consisting of DM patients with MSAs, low or high disease activity, and/or interstitial lung disease (DM-ILD) compared to age- and gender-matched healthy controls (HCs).RESULTS: The lipid profile in DM was found to be abnormal, especially dysregulated glycerophospholipid metabolism and fatty acid oxidation, which might affect the pathogenesis of DM by disrupting the balance of Th17 and Treg. We identified potential biomarkers of DM that can distinguish between low or high disease activity and reflect lung involvement. Two metabolite combinations including pro-leu, FA 14:0;O can distinguish high disease activity DM from low disease activity DM and HCs, and five including indole-3-lactic acid, dihydrosphingosine, SM 32:1;O2, NAE 17:1, and cholic acid can distinguish DM-ILD from DM without ILD (DM-nonILD). DM with different MSAs had unique metabolic characteristics, which can distinguish between MDA5+DM, Jo-1+DM, and TIF1-γ+DM, and from the antibody-negative groups. The sphingosine metabolism has been found to play an important role in MDA5+DM, which was associated with the occurrence of ILD.DISCUSSION: Altered metabolic profiles of dermatomyositis were associated with different myositisspecific autoantibodies, disease activity, and interstitial lung disease, which can help in the early diagnosis, prognosis, or selection of new therapeutic targets for DM.PMID:39654882 | PMC:PMC11625817 | DOI:10.3389/fimmu.2024.1429010

Front Vet Sci. 2024 Nov 25;11:1493284. doi: 10.3389/fvets.2024.1493284. eCollection 2024.ABSTRACTObese pig breeds have excellent meat quality, while lean pig breeds have high lean meat percentage and feed conversion rate. However, due to their respective shortcomings, obese pig and lean pig breeds are unable to balance production and consumption needs. Therefore, this study crossbred the obese Chinese pig breed Neijiang (NJ) with lean type Large White pigs (LW) to produce Neijiang × Large White(NL) pigs. This study compared the differences in carcass and meat quality traits between NJ pigs and NL pigs, and for the first time comprehensively analyzed the longissimus dorsi muscle of NJ pigs and NL pigs using transcriptomics and metabolomics. The results of slaughter and meat quality testing indicate that the carcass performance of NL pigs was significantly higher than that of NJ pigs, and the excellent meat quality characteristics of NJ pigs were also retained on NL pigs. The results of transcriptomics and metabolomics showed that there were 635 differentially expressed genes (DEGs) and 11 significantly different metabolites (SDM) in the longissimus dorsi muscle of NJ and NL pigs. The results of multi omics joint analysis showed that betaine, uridine triphosphate, glycerol 3-phosphate, and glutathione in SDMs were enriched in the shared KEGG pathway and significantly correlated with C1QTNF12, GGA3, SLC16A6, and RXRG in DEGs. In general, it is feasible to enhance the production performance of NJ pigs through crossbreeding with LW pigs. The hybrid offspring inherit the advantages of these two varieties, maintaining excellent meat quality while also having better carcass performance.PMID:39654839 | PMC:PMC11626801 | DOI:10.3389/fvets.2024.1493284

Front Bioeng Biotechnol. 2024 Nov 25;12:1497138. doi: 10.3389/fbioe.2024.1497138. eCollection 2024.ABSTRACTAs the natural producer of acarbose, Actinoplanes sp. SE50/110 has high industrial relevance. Like most Actinobacteria, the strain carries several more putative biosynthetic gene clusters (BGCs) to produce further natural products, which are to be discovered. Applying a metabolomics-guided approach, we tentatively identified five further compounds that are produced by the strain: watasemycin, thiazostatin, isopyochelin, pulicatin, and aerugine. A comparison of the genomic context allowed the identification of the putative BGC, which is highly similar to the watasemycin biosynthetic gene cluster of Streptomyces venezuelae. In addition to the identified molecules, a thiazostatin-like compound was found. Isolation and structure elucidation with 1D and 2D NMR and HRMS were applied. The fraction containing m/z 369.0929 [M + H]+ comprised two highly similar compounds identified as thiazostatin D and thiazostatin E. The compounds possessed the same phenol-thiazole-thiazole molecular scaffold as the previously reported thiazostatin and watasemycin and have anti-proliferative activity against the breast adenocarcinoma cell line MCF7 and human melanoma cell line A2058, while no activity again the non-malignant immortalized fibroblast cell line MRC-5 was observed. We further showed that the manipulation of global transcriptional regulators, with sigH (ACSP50_0507) and anti-anti-σ factor coding ACSP50_0284 as an example, enabled the production manipulation of the 2-hydroxyphenylthiazoline family molecules. While the manipulation of sigH enabled the shift in the peak intensities between the five products of this pathway, ACSP50_0284 manipulation prevented their production. The production of a highly polar compound with m/z 462.1643 [M + H]+ and calculated elemental composition C19H27NO12 was activated under the ACSP50_0284 expression and is exclusively produced by the engineered strain.PMID:39654828 | PMC:PMC11626248 | DOI:10.3389/fbioe.2024.1497138

Front Microbiol. 2024 Nov 25;15:1483680. doi: 10.3389/fmicb.2024.1483680. eCollection 2024.ABSTRACTThis study aimed to investigate the effects of dietary supplementation with zinc oxide nanoparticles (ZnONPs) on lactation, rumen microbiota, and metabolomics in dairy goats. Twenty Guanzhong dairy goats, with comparable milk yields and in the mid-lactation stage, were randomly divided into two groups, with 10 goats in each group. The control group was fed a standard diet, while the ZnONP group received the control diet plus 30 mg ZnONPs/kg DM. The pre-trial period lasted for 7 days, followed by a trial period of 30 days. The results showed that the addition of ZnONPs increased the milk yield and milk fat content (p < 0.05). The results of rumen microbial sequencing showed that the Chao1, Observed species, and PD_whole_tree indices of the ZnONP group were higher than those of the control group. The addition of ZnONPs altered the composition of the rumen microbiota, increasing the abundance of beneficial bacteria (Prevotella and Rikenellaceae_RC9_gut_group) and decreasing the abundance of the harmful bacterium Sediminispirochaeta. Non-targeted metabolomics analysis identified a total of 261 differential metabolites between the two groups, indicating changes in rumen metabolism. Further correlation analysis revealed a positive correlation between beneficial bacteria (Rikenellaceae RC9 gut group and Anaeroplasma) and metabolites such as nicotinamide riboside, inosine, and guanosine (p < 0.05). In addition, a positive correlation was observed between milk yield and beneficial bacteria (RF39 and Clostridia vadinBB60 group), as well as between milk fat content and Quinella (p < 0.05). In summary, ZnONP supplementation can improve the structure of the rumen microbiota in dairy goats, positively influencing milk yield, milk composition, and metabolism.PMID:39654678 | PMC:PMC11625748 | DOI:10.3389/fmicb.2024.1483680

Front Pharmacol. 2024 Nov 25;15:1491900. doi: 10.3389/fphar.2024.1491900. eCollection 2024.ABSTRACTBACKGROUND: Semen Cuscutae flavonoids (SCFs) constitute a class of metabolites of Semen Cuscutae, a botanical drug that was recently found to have an anti-depression effect. This study aimed to evaluate the anti-depression effects of SCFs in chronic unpredictable mild stress (CUMS)-induced mice and to interrogate the underlying mechanisms.MATERIALS AND METHODS: The CUMS mice were used for assessing the effects of SCFs treatments on depression. Mice were randomly divided into five groups. Four groups were subjected to the CUMS induction and concomitantly administered orally with either the vehicle or with a high-, medium-, and low-dose of SCFs, once per day for 4 weeks. One group was kept untreated as a control. The mice were then assessed for their statuses of a number of depression-related parameters, including body weight, food intake, sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST). In addition, a day after the completion of these tests, biopsies from the hippocampus were harvested and used to perform metabolomics by HPLC-MS/MS and to assess the levels of cAMP by ELISA and the levels of PKA, CREB, p-CREB, and BDNF by Western blot analyses.RESULTS: SCFs resulted in significant increases in both body weight and food intake and in the amelioration of the depressive-like behaviors in CUMS mice. A high-dose SCFs treatment led to significant alterations in 72 metabolites, of which 26 were identified as potential biomarkers for the SCFs treatment. These metabolites are associated with lipid, amino acid, and nucleotide metabolism. Among 26 metabolites, cAMP was positively correlated with body weight, SPT, OFT-total distance, and OFT-central residence time, while negatively correlated with immobility time in TST and FST, linking a change in cAMP with the SCFs treatment and the significant improvement in depressive symptoms in CUMS mice. Further analyses revealed that the levels of cAMP, PKA, CREB, p-CREB, and BDNF were reduced in the hippocampus of CUMS mice but were all increased following the SCFs treatments.CONCLUSION: SCFs could ameliorate hippocampal metabolic disturbances and depressive behaviors and cause the activation of the cAMP-PKA-CREB-BDNF signaling pathway in the hippocampus of CUMS mice.PMID:39654620 | PMC:PMC11625582 | DOI:10.3389/fphar.2024.1491900

Drug Des Devel Ther. 2024 Dec 5;18:5641-5654. doi: 10.2147/DDDT.S497212. eCollection 2024.ABSTRACTBACKGROUND: Dasatinib (DASA) is associated with cardiotoxic effects, posing risks to patients. Valsartan (VAL) may offer protective benefits against these effects. This study evaluates the impact of DASA, VAL, and their combination on cardiac health.METHODS: Wistar rats were treated with DASA, VAL, and a combination of VAL and DASA intraperitoneally every other day for 14 days. Body weight and survival rates were monitored. Serum levels of cardiac biomarkers (CPK, LDH, AST) were analyzed. Histopathological and immunohistochemical analyses assessed myocardial architecture and apoptosis-related protein expression. Metabolomic profiling was conducted using GC-MS to identify metabolic changes across treatment groups.RESULTS: The DASA group experienced significant weight loss and a 50% mortality rate, while the combination group had no mortality. Cardiac biomarkers like CPK, LDH, and AST were elevated in the DASA group but significantly reduced in the VAL + DASA group. Histopathological examination showed significant myocardial injury in the DASA group, with improved cardiac tissue morphology in the combination group. Immunohistochemical analysis revealed altered expression of apoptosis-related proteins, including caspase-3 and BCL-2, with improved levels in the combination group compared to DASA alone. Metabolomic profiling identified significant metabolic shifts, with 15 metabolites differentiating the treatment groups, and the VAL + DASA group mitigated the metabolic disturbances caused by DASA.CONCLUSION: The study suggesting VAL's potential therapeutic role in managing DASA-induced cardiac toxicity. The combination of VAL with DASA not only improved survival rates and reduced cardiac biomarker levels but also preserved myocardial architecture and normalized metabolic profiles. These findings highlight the importance of integrated approaches in evaluating drug efficacy and suggest VAL as a promising candidate for protecting cardiac function in preclinical models of DASA therapy.PMID:39654603 | PMC:PMC11626959 | DOI:10.2147/DDDT.S497212

Front Nutr. 2024 Nov 25;11:1505357. doi: 10.3389/fnut.2024.1505357. eCollection 2024.ABSTRACTINTRODUCTION: Fatty liver syndrome (FLS) is a prevalent nutritional and metabolic disease that mainly occurs in caged laying hens, causing substantial losses in the poultry industry. The study was carried out to explore the protective effect and potential mechanism of betaine on early FLS.METHODS: There were three groups: Con group (basal diet), FLS group (Dexamethasone injection + basal diet) and betaine group (Dexamethasone injection + basal diet with 8 g/kg betaine). Birds in FLS and betaine groups were treated with subcutaneous dexamethasone injection once a day at a dosage of 4.50 mg/kg body weight for 7 days.RESULTS: The results revealed that DXM treatment significantly increased the liver index, serum aspartate aminotransferase (AST), total protein (TP), total bilirubin (TBIL), total biliary acid (TBA), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and glucose (GLU) (p < 0.05). Additionally, hepatic TC and TG levels were also elevated (p < 0.05). Meanwhile, H&E and oil red O staining showed that there were a large number of vacuoles and lipid droplets in the liver of hens in FLS group. Dietary betaine addition significantly alleviated the increasing of serum TBIL, TBA and hepatic TC caused by dexamethasone treatment (p < 0.05). There existed 1,083 up- and 996 down-regulated genes in FLS group when compared with the control, and there were 169 upregulation and 405 downregulation genes in BT group when compared with FLS group. A total of 37 differential expression genes (DEGs) were rescued by betaine addition, which were related to lipid metabolism and antioxidant functions including APOC3, APOA4, G0S2, ERG28, PLA2G3, GPX4 and SLC5A8. Serum metabolomics analysis showed that 151 differential metabolites were identified in FLS group when compared with the control. Dietary betaine addition could rescue the changes of metabolites partly such as chicoric acid, gamma-aminobutyric acid, linoleic acid, telmisartan, which were associated with anti-oxidative function. In addition, RT-PCR results showed that genes involved in lipid metabolism, such as ACC, FAS, SCD1, ELOVL6, SREBP1, GR, ATGL and MTTP were markedly upregulated at the mRNA level (p < 0.05). However, dietary supplementation with betaine can reversed the expression of these genes (p < 0.05). Importantly, dietary betaine supplementation could reverse increased lipid synthesis partly by regulating PI3K/AKT/SREBP and CEBPα pathways in the liver based on western blot results (p < 0.05).CONCLUSION: Dexamethasone treatment could establish the early FLS model in laying hens with hepatic lipid accumulation and no inflammation, which could be attenuated by dietary betaine addition.PMID:39654538 | PMC:PMC11627039 | DOI:10.3389/fnut.2024.1505357

Front Nutr. 2024 Nov 25;11:1484257. doi: 10.3389/fnut.2024.1484257. eCollection 2024.ABSTRACTBACKGROUND: As albino tea under the geographical protection of agricultural products, Zheng'an Bai tea is not only rich in amino acids, polyphenols and other beneficial components for the human body, but also its leaf color will turn green as the temperature gradually rises, thus causing changes in the quality characteristics of tea leaves. However, these changing characteristics have not yet been revealed.METHODS: In-depth quality analysis was carried out on the fresh leaves of Zheng'an Bai tea at four different developmental stages and four samples from the processing stage through extensive targeted metabolomics and SPME-GC-MS analysis.RESULTS: In this study, a total of 573 non-volatile metabolites were detected from the fresh leaves and processing samples of Zheng'an Bai tea, mainly including 96 flavonoids, 75 amino acids, 56 sugars and alcohols, 48 terpenoids, 46 organic acids, 44 alkaloids, and 39 polyphenols and their derivatives. In fresh leaves, the most significant differential metabolites (VIP > 1, p < 0.05) among different samples mainly include substances such as ethyl gallate, theaflavin, isovitexin and linalool, while the main differential metabolites of samples in the processing stage include alkaloids, polyphenols and flavonoids such as zarzissine, methyl L-Pyroglutamate, theaflavin 3,3'-digallate, euscaphic acid and ethyl gallate. Overall, substances such as sugars and alcohols, alkaloids and polyphenols show the greatest differences between fresh leaves and the processing process. Meanwhile, 97 kinds of volatile metabolites were detected in these samples, most of which had a higher content in the fresh leaves. Moderate spreading is conducive to the release of the aroma of tea leaves, but fixation causes a sharp decrease in the content of most volatile metabolites. Ultimately, 9 volatile substances including geraniol, linalool, nerolidol, jasmone, octanal, 1-Nonanal, heptaldehyde, methyl salicylate and 1-Octen-3-ol were identified as the key aroma components (OAV >1) of Zheng'an Bai tea.CONCLUSION: In conclusion, this study has for the first time comprehensively revealed the quality change characteristics of fresh leaves at different developmental stages and during the processing of Zheng'an Bai tea, and provided a foundation for further process improvement.PMID:39654535 | PMC:PMC11625558 | DOI:10.3389/fnut.2024.1484257

J Agric Food Chem. 2024 Dec 9. doi: 10.1021/acs.jafc.4c08393. Online ahead of print.ABSTRACTUptake, translocation, and transformation mechanisms of tris(2-chloroethyl) phosphate (TCEP) in hydroponic wheat (Triticum aestivum L.) were systematically investigated using compound-specific stable isotope and multiomics analyses in this study. Results showed that TCEP was quickly adsorbed on root epidermis and then absorbed in roots via water and anion channels as well as an active process dependent on energy. Active process and anion channel preferentially translocated TCEP-containing light carbon isotopes and dominated the transmembrane transport of TCEP to enter vascular bundle. Transcriptomic and metabolomic analyses indicated gene-encoding ATP-binding cassette (ABC) transporters and purple acid phosphatases (PAPs) and glutathione S-transferases (GSTs) involved in TCEP transport and transformation, respectively. Molecular docking simulations showed that TCEP bound to the hydrophilic cavity of ABC transporter/PAP and hydrophobic cavity of GST, and hydrogen bonding was the important driving force. The results of this study offered insights for future effective mitigation of TCEP risk in edible plants.PMID:39654329 | DOI:10.1021/acs.jafc.4c08393

Nat Med. 2024 Dec 9. doi: 10.1038/s41591-024-03283-1. Online ahead of print.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies.PMID:39653777 | DOI:10.1038/s41591-024-03283-1

Commun Biol. 2024 Dec 9;7(1):1626. doi: 10.1038/s42003-024-07261-8.ABSTRACTThe microbial dimension of the terroir is crucial for wine quality, as microbiomes contribute to plant biofertilization, stress tolerance and pathogen suppression. While microbial terroir can act as a biological signature at large scale, data for local contexts is lacking, hindering the characterization of regional microbial diversity in vineyards. Here, we define the microbial terroir of vineyards across the 12 sub-areas (Additional Geographic Units -AGUs) of the "Consorzio del Vino Nobile di Montepulciano DOCG" PDO area (Italy), a world-renowned wine-producing region. Rhizospheres of Vitis vinifera cultivar Sangiovese and soil samples were collected throughout the 2022 viticultural season and analyzed through an integrated metabarcoding/shotgun metagenomic approach, targeting bacteria and fungi. Wine metabolomics was also perfomed, projecting compositional and functional variations of the microbial terroir at the AGUs level into a corresponding variation in the product metabolic profile. Our findings reveal a unique taxonomic configuration of the Vino Nobile di Montepulciano terroir compared to other vineyards, with microbiomes being "AGU-specific" in taxonomic abundances and plant growth-promoting functions, confirming the potential relevance of characterizing and preserving the microbial terroir to safeguard high-quality traditional wines.PMID:39653697 | DOI:10.1038/s42003-024-07261-8