PubMed

Int J Endocrinol. 2024 Oct 28;2024:5540062. doi: 10.1155/2024/5540062. eCollection 2024.ABSTRACTBackground: Type 2 diabetes mellitus (T2DM) has emerged as a global epidemic issue, with high rates of disability and fatality. Traditional diagnostic biomarkers are typically detected once a metabolic imbalance has already occurred, thus the development of early diagnostic biomarkers is crucial for T2DM. Metabolomics studies have identified several predictive biomarkers for T2DM, including miR-320. Our previous research found that miR-320b was significantly downregulated in T2DM patients, but the underlying mechanism remains unclear. Therefore, this study was designed to investigate the significance of miR-320b for T2DM diagnosis and to explore the involved molecular mechanism. Methods: A total of 50 patients with T2DM and 80 sex- and age-matched healthy subjects were selected. The plasma miR-320b of all participations was detected by qRT-PCR and its correlations with other biomarkers of T2DM were analyzed. Besides, the expression of miR-320b in HepG2 cells was suppressed by miRNA inhibitors. Then the glucose consumption of HepG2 cells was measured. The target gene of miR-320b was predicted by four bioinformatics tools and intersected these prediction results by Venny method. The T2DM relevant target genes were identified by the GeneCards database. To ensure disease relevance, these T2DM relevant target genes were subsequently intersected with the target genes of miR-320b. Protein-protein analysis (PPI) was used to screening the gene with the most connections in these target genes. Finally, the target gene of miR-320b specific to T2DM was confirmed directly by luciferase reporter assay. The expression of target gene in HepG2 cell culture supernatant and plasma of all participations was detected. Results: Our results showed that the expression level of miR-320b was significantly lower in T2DM patients compared to the healthy controls. It was negatively correlated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and homeostasis model assessment of insulin resistance (HOMA-IR), but positively with HOMA-β. The glucose consumption of HepG2 cells in the miR-320b inhibitor group was significantly lower compared to inhibitor-NC and blank control group. We predicted and confirmed that phosphatase and tensin homolog (PTEN) was the direct target gene of miR-320b using Bioinformation tools and luciferase reporter assay. Moreover, the concentration of PTEN was significantly higher in the HepG2 cell culture supernatant and plasma of T2DM patients. Conclusions: Our research demonstrated a negative correlation between miR-320b and FPG, HbA1C, and HOMA-IR, while exhibiting a positive correlation with HOMA-β. Suppressing miR-320b expression would impair glucose consumption of HepG2 cells through PI3K pathway by targeting PTEN. These results suggest that miR-320b may be a potential biomarker for diagnosing T2DM and a promising target for therapeutic intervention.PMID:39502509 | PMC:PMC11535181 | DOI:10.1155/2024/5540062

Front Oral Health. 2024 Oct 22;5:1475361. doi: 10.3389/froh.2024.1475361. eCollection 2024.ABSTRACTINTRODUCTION: During development of dental caries, oral biofilms undergo changes in microbial composition and phenotypical traits. The aim of this study was to compare the acid tolerance (AT) of plaque from two groups of children: one with severe caries (CA) and one with no caries experience (CF) and to correlate this to the microbial composition and metabolic profile of the biofilms.METHODS: Dental plaque samples from 20 children (2-5 years) in each group were studied. The AT was analyzed by viability assessment after exposure to an acid challenge (pH 3.5), using LIVE/DEAD® BacLight™ stain and confocal microscopy. Levels of acid tolerance (AT) were evaluated using a scoring system ranging from 1 (no/low AT), to 5 (high/all AT). Metabolic profiles were investigated following a 20 mM glucose pulse for one hour through Nuclear Magnetic Resonance (NMR). Microbial composition was characterized by 16S rRNA Illumina sequencing.RESULTS: The mean AT score of the CA group (4.1) was significantly higher than that of the CF group (2.6, p < 0.05). When comparing the end-products of glucose metabolism detected after a glucose-pulse, the CA samples showed a significantly higher lactate to acetate, lactate to formate, lactate to succinate and lactate to ethanol ratio than the CF samples (p < 0.05). The bacterial characterization of the samples revealed 25 species significantly more abundant in the CA samples, including species of Streptococcus, Prevotella, Leptotrichia and Veillonella (p < 0.05).DISCUSSION: Our results show that AT in pooled plaque from the oral cavity of children with severe caries is increased compared to that in healthy subjects and that this can be related to differences in the metabolic activity and microbial composition of the biofilms. Thus, the overall phenotype of dental plaque appears to be a promising indicator of the caries status of individuals. However, longitudinal studies investigating how the AT changes over time in relation to caries development are needed before plaque AT could be considered as a prediction method for the development of dental caries.PMID:39502319 | PMC:PMC11534697 | DOI:10.3389/froh.2024.1475361

J Sci Food Agric. 2024 Nov 6. doi: 10.1002/jsfa.13996. Online ahead of print.ABSTRACTBACKGROUND: Brassica juncea L. (family Brassicaceae) or Indian mustard is a fast-growing oilseed crop. Climate changes mean that it is very important to evaluate the effects of salinity stress on B. juncea. The aim of this study was therefore to show the metabolic effect of salinity stress on shoots and roots using two cultivation models - hydroponic and microplot - in different cultivars, including RH-725 and RH-761. Salinity levels of 5, 7.5, and 10 dS m⁻¹ were investigated, and compared with a control of 0 dS m⁻¹, using untargeted metabolomics with gas chromatography-mass spectrometry (GC-MS) post-silylation, focusing on metabolic markers such as proline and glycine-betaine.RESULTS: A total of 56 metabolites were identified, with the most prevalent classes belonging to sugars (8), followed by organic acids (13), amino acids (11), and fatty acids/esters (11). Shoots were found to have a higher sugar content than roots. Increases in unsaturated fatty acids were also associated with salinity stress, compared with a decrease in saturated fatty acids. Absolute levels of proline and glycine-betaine correlated with salinity stress, with the largest increases detected in shoots grown under hydroponic conditions, particularly for the RH-761 cultivar. Multivariate data analyses revealed that roots were more affected than shoots, regardless of cultivation model.CONCLUSION: These findings might explain the different metabolic behavior of B. juncea's roots and shoots under various levels of salinity, associated with higher levels of free sugars in shoots and lipids in roots. © 2024 Society of Chemical Industry.PMID:39502065 | DOI:10.1002/jsfa.13996

Curr Neuropharmacol. 2024 Nov 4. doi: 10.2174/1570159X23666241101093436. Online ahead of print.ABSTRACTBACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy.CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.PMID:39501955 | DOI:10.2174/1570159X23666241101093436

J Agric Food Chem. 2024 Nov 6. doi: 10.1021/acs.jafc.4c07140. Online ahead of print.ABSTRACTCasein hydrolysates have been proven to exert varying sleep-enhancing and anxiolytic effects due to their distinct release of potential peptides. However, their underlying sleep-enhancing mechanisms at the metabolic level remain unclear. This study aims to investigate the potential sleep-enhancing mechanism of casein hydrolysates through an integrated approach of untargeted and targeted metabolomics in CUMS-induced anxiety mice for the first time. The results showed seven potential biomarkers were identified and screened using orthogonal partial least-squares discriminant analysis, random forest model, and pathway analysis, including ornithine, l-proline, l-prolinamide, inhibitory neurotransmitters gamma-aminobutyric acid, 5-HIAA, fumaric acid, and 4-oxoglutaramate. Moreover, casein hydrolysates exerted sleep-enhancing effects through multiple metabolic pathways, mainly including the GABAergic system, tryptophan metabolism, and cAMP response signaling pathway, which was validated by targeted metabolomics and vital protein expressions. It was interesting that casein hydrolysates with diverse representative peptide compositions exhibited varying activity, which could be attributed to distinct alterations in metabolites via different pathways.PMID:39501924 | DOI:10.1021/acs.jafc.4c07140

Physiol Plant. 2024 Nov-Dec;176(6):e14598. doi: 10.1111/ppl.14598.ABSTRACTSaffron stigma, derived from Crocus sativus L., has long been revered in global traditional medicine and continues to hold significant market value. However, despite the extensive focus on saffron stigma, the therapeutic potential of other floral components remains underexplored, primarily due to limited insights into their complex molecular architectures and chemical diversity. To address this gap, we performed a comprehensive metabolomic analysis of various floral organs utilizing advanced analytical platforms, including GC-MS and UPLC-MS/MS. This in-depth profiling revealed a diverse array of 248 metabolites, encompassing amino acids, sugar derivatives, fatty acids, flavonoids, vitamins, polyamines, organic acids, and a broad spectrum of secondary metabolites. Distinct correlation patterns among these metabolites were identified through PCA and PLS-DA, highlighting unique metabolomic signatures inherent to each floral organ. We further integrated these metabolomic findings with our transcriptomic data, enabling a detailed understanding of the molecular and metabolic variations across different floral organs. The pronounced abundance of differentially expressed genes and metabolites in the stamen (424), leaf (345), tepal (196), stigma (177), and corm (133) underscores the intricate regulatory networks governing source-to-sink partitioning and dynamic metabolic processes. Notably, our study identified several bioactive compounds, including crocin, picrocrocin, crocetin, safranal, cannabielsoin, quercetin, prenylnaringenin, isorhamnetin, pelargonidin, kaempferol, and gallic acid, all of which exhibit potential therapeutic properties. In conclusion, this comprehensive analysis significantly enhances our understanding of the molecular mechanisms driving the biosynthesis of apocarotenoids, cannabinoids, anthocyanins, and flavonoids in saffron, thereby providing valuable insights and paving the way for future research in this area.PMID:39501843 | DOI:10.1111/ppl.14598

Aging Cell. 2024 Nov 5:e14395. doi: 10.1111/acel.14395. Online ahead of print.ABSTRACTA new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline. We hypothesized that timing of menopause, a marker of ovarian aging, predicts brain age decades later. We used 2086 subjects with multiple "omics" measurements from post-mortem brain samples. Age at menopause (AAM) is positively correlated with cognitive function and negatively correlated with pre-frontal cortex aging acceleration (calculated as estimated biological age from DNA methylation minus chronological age). Genetic correlations showed that at least part of these associations is derived from shared heritability. To dissect the mechanism linking AAM to cognitive decline, we turned to transcriptomic data which confirmed that later AAM was associated with gene expression in pre-frontal cortex consistent with better cognition, and among those who reached menopause naturally, decreased gene expression of pathways implicated in aging. Those with surgical menopause displayed different molecular changes, including perturbed nicotinamide adenine dinucleotide (NAD+) activity, validated by metabolomics. Bile acid metabolism was perturbed in both groups, although different bile acid ratios were associated with AAM in each. Together, our data suggest that AAM is predictive of brain aging and cognition, with potential mediation by the gut, although through different mechanisms depending on the type of menopause.PMID:39501567 | DOI:10.1111/acel.14395

Plant Cell Environ. 2024 Nov 5. doi: 10.1111/pce.15261. Online ahead of print.ABSTRACTPigeon pea, vital for farmers in semi-arid regions, suffers yield losses from Fusarium wilt caused by Fusarium udum. This study demonstrates that introducing the rice oxalate oxidase 4 (Osoxo4) gene significantly boosts wilt resistance. Enhanced resistance in transgenic lines was confirmed through gene expression analysis, enzyme activity assays, biochemical assessments, histochemical staining and in vitro and in vivo bioassays, including spore germination tests. We performed proteomics and metabolomics analyses to investigate mechanisms of enhanced resistance. LC-MS/MS-based label-free proteomics of wilt-infected transgenic and wild-type pigeon pea leaves identified 2386 proteins, with 1048 showing significant abundance changes-738 upregulated and 310 downregulated-in transgenic plants. Notably, proteins such as HMG1/2-like protein, Putative nucleosome assembly protein C364.06, DEAD-box ATP-dependent RNA helicase 3, Lipoxygenase 1, Annexin D1 and Annexin-like protein RJ4 were significantly upregulated, indicating their potential role in developing wilt-resistant cultivars. Metabolomic analysis showed elevated levels of amino acids, sugars, oxalic acid, sugar alcohols and myo-inositol in transgenic pigeon pea, with upregulated pathways in Sugar and Starch Metabolism and Inositol Phosphate Metabolism, indicating enhanced resilience to wilt stress. This study highlights unique regulatory proteins and metabolites, offering insights into stress adaptation and guiding genetic interventions for breeding disease-resistant pigeon pea varieties.PMID:39501468 | DOI:10.1111/pce.15261

J Anim Physiol Anim Nutr (Berl). 2024 Nov;108(6):1650-1664. doi: 10.1111/jpn.14008. Epub 2024 Jun 21.ABSTRACTThe world's increasing need for protein faces challenges in aquaculture production. New applications and tools will need to be added at every stage of the manufacturing line to attain this expansion sustainably, safely, and effectively. Utilizing experimental methods to increase aquatic animal production has become more common as aquatic biotechnology has advanced. High-throughput omics technologies have been introduced to address these issues, including transcriptomic, metabolomic, proteomic, and genomes. But it also faces many difficulties, like other food manufacturing industries. One of the best and most durable approaches to address these issues is probably to understand nutritional requirements and modify diet based on need. Molecular approaches are a subset of multiomics technology. Previously, most of the published work was devoted to the biochemical aspects of protein-lipid interactions in biological systems. In this review, we explore this idea and highlight various works that fall under the umbrella of nutrigenomics, with a particular emphasis on protein utilization and its interactions with carbohydrates and lipids.PMID:39501455 | DOI:10.1111/jpn.14008

Virol J. 2024 Nov 6;21(1):278. doi: 10.1186/s12985-024-02553-1.ABSTRACTBACKGROUND: Researchers gradually focus on the relationship between phage and cancer.OBJECTIVE: To summarize the research hotspots and trends in the field of bacteriophage and cancer.METHODS: The downloaded articles were searched from the Web of Science Core Collection database from January 2008 to June 2023. Bibliometric analysis was carried out through CiteSpace, including the analysis of cooperative networks (country/region, institution, and author), co-citations of references, and key words.Visual analysis of three topics, including gut phage, phage and bacteria, and phage and tumor, was conducted.RESULTS: Overall, the United States and China have the most phage-related research. In terms of gut phage, the future research directions are "gut microbiome", "database" and "microbiota". The bursting citations explored the phage-dominated viral genome to discover its diversity and individual specificity and investigated associations among bacteriome, metabolome, and virome. In terms of phage and bacteria, "lipopolysaccharide" and "microbiota" are future research directions. Future research hotspots should mainly concentrate on the further exploration and application of phage properties. As for phages and tumors, the future research directions should be "colorectal cancer", "protein" and "phage therapy". Future directions are likely to focus on the research on phages in cancer mechanisms, cancer diagnosis, and cancer treatment combined with genetic engineering techniques.CONCLUSION: Phage therapy would become a hot spot and research direction of tumor and phage research, and the relationship between phage and tumor, especially colorectal cancer (CRC), is expected to be further explored.PMID:39501333 | DOI:10.1186/s12985-024-02553-1

J Neuroinflammation. 2024 Nov 5;21(1):287. doi: 10.1186/s12974-024-03270-w.ABSTRACTBACKGROUND: Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation.METHODS: We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients.RESULTS: We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential.CONCLUSION: Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.PMID:39501296 | DOI:10.1186/s12974-024-03270-w

BMC Genomics. 2024 Nov 5;25(1):1042. doi: 10.1186/s12864-024-10939-2.ABSTRACTBACKGROUND: Pumpkin (Cucurbita moschata) is an important vegetable crop that often suffers from low-temperature stress during growth. However, the molecular mechanism involved in its response to chilling stress remains unknown. In this study, we comprehensively investigated the effect of chilling stress in pumpkin seedlings by conducting physiological, transcriptomic, and metabolomic analyses.RESULTS: Under chilling stress, there was an overall increase in relative electrical conductivity, along with malondialdehyde, soluble sugar, and soluble protein contents, but decreased superoxide dismutase and peroxidase activities and chlorophyll contents in seedling leaves compared with controls. Overall, 5,780 differentially expressed genes (DEGs) and 178 differentially expressed metabolites (DEMs) were identified under chilling stress. Most DEGs were involved in plant hormone signal transduction and the phenylpropanoid biosynthesis pathway, and ERF, bHLH, WRKY, MYB, and HSF transcription factors were induced. Metabolomic analysis revealed that the contents of salicylic acid (SA), phenylalanine, and tyrosine increased in response to chilling stress. The findings indicated that the SA signaling and phenylpropanoid biosynthesis pathways are key to regulating the responses to chilling stress in pumpkins.CONCLUSION: Overall, our study provides valuable insights into the comprehensive response of C. moschata to chilling stress, enriching the theoretical basis of this mechanism and facilitating the development of molecular breeding strategies for pumpkin tolerance to chilling stress.PMID:39501146 | DOI:10.1186/s12864-024-10939-2

Commun Biol. 2024 Nov 5;7(1):1436. doi: 10.1038/s42003-024-07166-6.ABSTRACTPredation reduces the population density of prey, affecting its fitness and population dynamics. Few studies have connected trait changes with fitness consequences in prey and the molecular basis and metabolic mechanisms of such changes in bat-insect systems. This study focuses on the responses of Helicoverpa armigera to different predation risks, focusing on echolocating bats and their calls. Substantial modifications were observed in the nocturnal and diurnal activities of H. armigera under predation risk, with enhanced evasion behaviors. Accelerated development and decreased fitness were observed under predation risks. Transcriptomic and metabolomic analyses indicated that exposure to bats induced the upregulation of amino acid metabolism- and antioxidant pathway-related genes, reflecting shifts in resource utilization in response to oxidative stress. Exposure to bat predation risks enhanced the activity of DNA damage repair pathways and suppressed energy metabolism, contributing to the observed trait changes and fitness decreases. The current results underscore the complex adaptive strategies that prey species evolve in response to predation risk, enhancing our understanding of the predator-prey dynamic and offering valuable insights for innovative and ecologically informed pest management strategies.PMID:39501073 | DOI:10.1038/s42003-024-07166-6

Sci Rep. 2024 Nov 5;14(1):26816. doi: 10.1038/s41598-024-78603-z.ABSTRACTAcne is a prevalent inflammatory disease in dermatology, and its pathogenesis may be associated with inflammation, immunity, and other mechanisms. It commonly manifests in young individuals and frequently imposes a heavy economic, physical, and psychological burden on patients. Gut microbes and blood metabolites, as significant immune and inflammatory regulators in the body, have been hypothesized to form the "neurocutaneous axis." Nonetheless, the precise causal relationships among the gut microbes, circulating blood metabolites, and acne development have yet to be elucidated. This study employed bidirectional two-sample Mendelian randomization (MR) to probe the causal impacts of 412 distinct gut microbes and 249 blood metabolites on acne. Single nucleotide polymorphisms (SNPs), which are closely associated with gut microbes and blood metabolites, were utilized as instrumental variables. This approach was taken to discern whether these elements serve as pathogenic or protective factors in relation to acne. Furthermore, a mediation analysis encompassing gut microbes, blood metabolites, and acne was conducted to explore potential correlations between gut microbes and blood metabolites, as well as their cumulative effects on acne. This was done to substantiate the notion of causality. Bidirectional two-sample MR analysis revealed 8 gut bacteria, 6 bacterial metabolic abundance pathways determined by birdshot, and 8 blood metabolites significantly associated with acne. The mediation MR analysis revealed 2 potential causal relationships, namely, Bifidobacterium-DHA-Acne and Bifidobacterium-Degree of Unsaturation-Acne. This study identified gut microbes and blood metabolites that are causally associated with acne. A potential causal relationship between gut microbes and blood metabolites was obtained via mediation analysis. These insights pave the way for the identification of new targets and the formulation of innovative approaches for the prevention and treatment of acne.PMID:39501024 | DOI:10.1038/s41598-024-78603-z

Cell Death Dis. 2024 Nov 6;15(11):795. doi: 10.1038/s41419-024-07177-5.ABSTRACTOsteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.PMID:39500875 | DOI:10.1038/s41419-024-07177-5

J Immunother Cancer. 2024 Nov 5;12(11):e010422. doi: 10.1136/jitc-2024-010422.ABSTRACTBACKGROUND: Immune checkpoint inhibitors (ICIs) are therapeutically effective for hepatocellular carcinoma (HCC) but are individually selective. This study examined the role of specific common fragile sites (CFSs) related gene in HCC immunotherapy.METHODS: We analyzed HCC tissues using next-generation sequencing and flow cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay were used to examine the function and mechanism of WWOX in the tumor immune response.RESULTS: WWOX was the most upregulated CFS-related gene in HCC patients responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in humanized orthotopic HCC mouse model. Macrophage infiltration is increased and CD8 T-cell subset infiltration is decreased in WWOX-deficient HCC patients. HCC-derived oleic acid (OA) promotes macrophage conversion to an immunosuppressive phenotype. Mechanistically, WWOX deficiency promoted OA synthesis primarily via competitive binding of NME2 with KAT1, which promoted acetylation of NME2 at site 31 and inhibited NME2 binding to the SCD5 promoter region. Pharmacological blockade of SCD5 enhanced the antitumor effects of anti-PD-1 therapy.CONCLUSIONS: WWOX is a key factor for immune escape in HCC patients, which suggests its use as a biomarker for stratified treatment with ICIs in clinical HCC patients.PMID:39500530 | DOI:10.1136/jitc-2024-010422

Int J Cardiol. 2024 Nov 3:132698. doi: 10.1016/j.ijcard.2024.132698. Online ahead of print.ABSTRACTBACKGROUND: Dyslipidaemia in patients with diabetes contributes to the risk of atherosclerotic cardiovascular disease. We aimed to identify a dyslipidemic profile associated with both dysglycemia and subclinical coronary atherosclerosis.METHODS: Study participants (n = 5050) were classified in three groups: normoglycemia, pre-diabetes, and diabetes. A coronary artery calcium score (CACS) > 0 defined subclinical coronary atherosclerosis. Two independent methods were used to identify, among 225 lipid biomarkers, those that were associated with pre-diabetes and diabetes and had to be further tested for association by zero inflated Poisson regression with CACS and CACS burden in those with CACS>0. Estimates were adjusted for cardiovascular risk factors with an interaction term for dispensed lipid lowering drugs.RESULTS: Thirty-two biomarkers associated with prediabetes and diabetes were further investigated for association with CACS. HDL diameter [multi-adjusted OR of 0.85 and 95 %CI (0.78-0.92)] as well as free cholesterol, phospholipids and total lipids in extra large HDL were inversely associated with CACS. There was a borderline significant interaction between small HDL and dispensed lipid lowering drugs on the presence of CACS, with and multi-adjusted OR of 0.53 and 95 %CI (0.36-0.77). None of the 32 glycemic profile-related lipid biomarkers associated with the relative increase of CACS in those with CACS>0. No consistent association was observed between non-HDL lipoproteins and CACS.CONCLUSIONS: Changes in composition and relative concentration of HDL associated with both dysglycemia and subclinical coronary atherosclerosis. Treatment with lipid lowering drugs may contribute to reduce the risk associated with high circulating levels of small HDL.PMID:39500476 | DOI:10.1016/j.ijcard.2024.132698

Poult Sci. 2024 Oct 29;103(12):104453. doi: 10.1016/j.psj.2024.104453. Online ahead of print.ABSTRACTThe differences in metabolites between fresh egg yolk (FEY), spray-dried egg yolk powder (SEY), and stored egg yolk powder (S-SEY) were quantitatively compared through metabolomic analysis. Total of 1004 metabolites were identified in the three groups of egg yolk samples. In pairwise group analysis, 242 differential metabolites were identified in FEY and SEY, 311 differential metabolites were identified in FEY and S-SEY, and 157 differential metabolites were identified in SEY and S-SEY. The analysis of differential metabolites with the highest abundance showed that amino acids, carbohydrates and lipids in FEY would undergo oxidation reactions after spray drying and storage and thus led to significant changes in the type and abundance of metabolites. The representative differential metabolites were then screened out for judging the freshness of egg yolk powder. Therefore, the results are highly important for evaluating the quality of egg yolk powder and provide important information for understanding the nutritional changes of egg yolk after spray drying and storage.PMID:39500265 | DOI:10.1016/j.psj.2024.104453

J Hazard Mater. 2024 Oct 31;480:136381. doi: 10.1016/j.jhazmat.2024.136381. Online ahead of print.ABSTRACTDi-(2-ethylhexyl) phthalate (DEHP) and microplastics (MPs) are emerging contaminants frequently detected in the marine environment. However, the influence of MPs on DEHP bioaccumulation and their combined effects on eco-environmental risks remain underexplored. Mytilus coruscus (M. coruscus) were exposed to DEHP (200.0 µg/L), polystyrene (PS) (0.050, 0.50, and 5.0 mg/L), and their combination at environmentally relevant concentrations for 15-day, followed by a 7-day depuration period. The amount of DEHP accumulation followed the order of digestive gland > gills > muscles > gonad, with PS dose-dependently amplifying DEHP bioaccumulation in digestive gland. The changes in antioxidant enzyme activity indicated disruptions in oxidative defense. Furthermore, metabolomic analysis revealed that PS and DEHP considerably altered the lipid, energy, and citric acid cycles in digestive gland and gonad. Post-depuration analysis showed combined exposure resulted in persistent effects. Compared with single exposures, combined exposure had a greater adverse effect on the metabolism of essential amino acids, fatty acids, and volatile compounds, potentially influencing edibility and nutritional value of M. coruscus. This study underscores cumulative eco-environmental toxicity of PS and DEHP toward M. coruscus and highlights the potential increased risks of co-pollution.PMID:39500187 | DOI:10.1016/j.jhazmat.2024.136381

J Environ Manage. 2024 Nov 4;371:123176. doi: 10.1016/j.jenvman.2024.123176. Online ahead of print.ABSTRACTThe secretion, accumulation, and composition of extracellular polymeric substances (EPS) are pivotal factors influencing microalgal growth as well as wastewater recycling. Until now, the accumulation and inhibition mechanism of EPS of Chlorella vulgaris during cycling cultivation is not fully understood. The purpose of this study was to explore how different light qualities regulate the secretion, chemical composition, and structure of microalgal EPS, and subsequently influence the recycling of culture wastewater. After four cycles of cultivation, C. vulgaris under green light produced the highest EPS production and lowest biomass production, which were 82% higher and 17% lower, respectively, compared to white light, which yielded the least EPS production and the highest biomass production. EPS under different light qualities all exhibited a fibrillar structure with a sheet-like surface, but differed in composition. Compared with the other groups, EPS under green light showed a significant increase in polysaccharides, proteins, and humic acid-like compounds, as well as an increased proportion of arabinose and rhamnose, according to monosaccharide composition analysis. Transcriptome analysis indicated that the up-regulation of metabolic pathways linked to glycolysis/gluconeogenesis, TCA cycle, lipid synthesis, and ABC transporters promoted EPS accumulation. Additionally, EPS could target light-harvesting complex (LHC) and electron transport chain, down-regulating the photosynthetic pathway, which ultimately inhibited microalgal growth under green light. This study provides a theoretical foundation for the light regulation and circulation culture of microalgae, as well as for microalgal wastewater treatment.PMID:39500171 | DOI:10.1016/j.jenvman.2024.123176