PubMed

J Hazard Mater. 2023 Sep 21;461:132602. doi: 10.1016/j.jhazmat.2023.132602. Online ahead of print.ABSTRACTExposure to ambient fine particulate matter (PM2.5) has been linked to a decline in semen quality, but the underlying mechanisms for this association remain unclear. We aimed to examine whether specific metabolites act as mediators in the association between PM2.5 exposure and changes in semen quality. We conducted untargeted metabolomics analysis using LC-MS/MS platforms to identified seminal plasma metabolites associated with various semen quality parameters among 200 Chinese adult men. Additionally, we performed mediation analyses to examine the effects of the seminal plasma metabolites on the association between PM2.5 exposure and semen quality. We identified 140 differential metabolites between the normal and abnormal semen groups, involving two metabolic pathways: Alanine, aspartate and glutamate metabolism, and Aminoacyl-tRNA biosynthesis. We additionally identified 7 specific seminal plasma metabolites that were associated with discrepant metabolic networks related to semen quality. The mediation analysis revealed that D-Aspartate might play a mediating role in the adverse effects of ambient PM2.5 exposure on both total and progressive motility during spermatogenesis period (70-90 days before ejaculation), with a proportion of mediation up to 16% and 17%, respectively. Exposure to PM2.5 was associated with alterations in D-Aspartate levels, which might partially mediate the association between PM2.5 and reduced sperm motility.PMID:37748305 | DOI:10.1016/j.jhazmat.2023.132602

J Exp Clin Cancer Res. 2023 Sep 25;42(1):248. doi: 10.1186/s13046-023-02803-0.ABSTRACTBACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown.METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments.RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC.CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.PMID:37749638 | DOI:10.1186/s13046-023-02803-0

Stem Cell Res Ther. 2023 Sep 25;14(1):271. doi: 10.1186/s13287-023-03471-9.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4+T homeostasis.RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.PMID:37749611 | DOI:10.1186/s13287-023-03471-9

J Med Chem. 2023 Sep 25. doi: 10.1021/acs.jmedchem.3c00517. Online ahead of print.ABSTRACTTargeted protein degradation (TPD) has emerged as the most promising approach for the specific knockdown of disease-associated proteins and is achieved by exploiting the cellular quality control machinery. TPD technologies are highly advantageous in overcoming drug resistance as they degrade the whole target protein. Microtubules play important roles in many cellular processes and are among the oldest and most well-established targets for tumor chemotherapy. However, the development of drug resistance, risk of hypersensitivity reactions, and intolerable toxicities severely restrict the clinical applications of microtubule-targeting agents (MTAs). Microtubule degradation agents (MDgAs) operate via completely different mechanisms compared with traditional MTAs and are capable of overcoming drug resistance. The emergence of MDgAs has expanded the scope of TPD and provided new avenues for the discovery of tubulin-targeted drugs. Herein, we summarized the development of MDgAs, and discussed their degradation mechanisms, mechanisms of action on the binding sites, potential opportunities, and challenges.PMID:37748178 | DOI:10.1021/acs.jmedchem.3c00517

Stroke. 2023 Oct;54(10):e442-e443. doi: 10.1161/STROKEAHA.123.044481. Epub 2023 Sep 25.NO ABSTRACTPMID:37747967 | DOI:10.1161/STROKEAHA.123.044481

PLoS One. 2023 Sep 25;18(9):e0291798. doi: 10.1371/journal.pone.0291798. eCollection 2023.ABSTRACTAt high altitudes, oxygen deprivation can cause pathophysiological changes. Liver tissue function is known to impact whole-body energy metabolism; however, how these functions are affected by chronic hypoxia remains unclear. We aimed to elucidate changing characteristics underlying the effect of chronic hypoxia on protein and amino acid metabolism in mouse livers. Mice were maintained in a hypobaric chamber simulating high altitude for 4 weeks. Livers were collected for metabolomic analysis via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. For transcriptomics analysis, we conducted RNA sequencing of hepatic tissues followed by Gene Ontology and KEGG pathway enrichment analyses. Chronic hypoxic exposure caused metabolic disorders of amino acids and their derivatives in liver tissue. We identified a number of metabolites with significantly altered profiles (including amino acids, peptides, and analogues), of which serine, phenylalanine, leucine, proline, aspartic acid, L-glutamate, creatine, 5-aminovaleric acid, L-hydroxyarginin, and g-guanidinobutyrate showed great potential as biomarkers of chronic hypoxia. A total of 2124 genes with significantly different expression levels were identified in hypoxic liver tissue, of which 1244 were upregulated and 880 were downregulated. We found pathways for protein digestion and absorption, arginine and proline metabolism, and mineral absorption related to amino acid metabolism were affected by hypoxia. Our findings surrounding the regulation of key metabolites and differentially expressed genes provide new insights into changes in protein and amino acid metabolism in the liver that result from chronic hypoxia.PMID:37747892 | DOI:10.1371/journal.pone.0291798

Pediatr Allergy Immunol. 2023 Sep;34(9):e14021. doi: 10.1111/pai.14021.NO ABSTRACTPMID:37747754 | DOI:10.1111/pai.14021

Am J Physiol Cell Physiol. 2023 Sep 25. doi: 10.1152/ajpcell.00316.2023. Online ahead of print.ABSTRACTSarcoidosis is a complex inflammatory fibrotic disease that affects multiple organ systems. It is characterised by the infiltration of lymphocytes and mononuclear phagocytes, which form non-caseating granulomas in affected organs. The lungs and intrathoracic lymph nodes are the most commonly affected organs. The underlying cause of sarcoidosis is unknown, but it is believed to occur in genetically predisposed individuals who are exposed to pathogenic organisms, environmental contaminants, or self and non-self-antigens. Recent research has suggested that the microbiome may play a role in the development of respiratory conditions, including sarcoidosis. Additionally, metabolomic studies have identified potential biomarkers for monitoring sarcoidosis progression. This review will focus on recent microbiome and metabolomic findings in sarcoidosis, with the goal of shedding light on the pathogenesis and possible diagnostic and therapeutic approaches.PMID:37746695 | DOI:10.1152/ajpcell.00316.2023

Anim Nutr. 2023 Jul 15;15:10-21. doi: 10.1016/j.aninu.2023.02.012. eCollection 2023 Dec.ABSTRACTBeta-hydroxybutyric acid (BHBA), as one of the main metabolic ketones in the rumen epithelium, plays critical roles in cellular growth and metabolism. The ketogenic capacity is associated with the maturation of rumen in young ruminants, and the exogenous BHBA in diet may promote the rumen development. However, the effects of exogenous BHBA on rumen remain unknown. This is the first study to investigate the mechanisms of BHBA on gene expression and metabolism of rumen epithelium using young goats as a model through multi-omics techniques. Thirty-two young goats were divided into control, low dose, middle dose, and high dose groups by supplementation of BHBA in starter (0, 3, 6, and 9 g/day, respectively). Results demonstrated the dietary of BHBA promoted the growth performance of young goats and increased width and length of the rumen papilla (P < 0.05). Hub genes in host transcriptome that were positively related to rumen characteristics and BHBA concentration were identified. Several upregulated hub genes including NDUFC1, NDUFB4, NDUFB10, NDUFA11 and NDUFA1 were enriched in the gene ontology (GO) pathway of nicotinamide adenine dinucleotide (NADH) dehydrogenase (ubiquinone) activity, while ATP5ME, ATP5PO and ATP5PF were associated with ATP synthesis. RT-PCR revealed the expression of genes (HMGCS2, BDH1, SLC16A3, etc.) associated with lipolysis increased significantly by BHBA supplementation (P < 0.05). Metabolomics indicated that some metabolites such as glucose, palmitic acid, cortisol and capric acid were also increased (P < 0.05). This study revealed that BHBA promoted rumen development through altering NADH balance and accelerating lipid metabolism, which provides a theoretical guidance for the strategies of gastrointestinal health and development of young ruminants.PMID:37746660 | PMC:PMC10514413 | DOI:10.1016/j.aninu.2023.02.012

Front Fungal Biol. 2022 Feb 14;3:808578. doi: 10.3389/ffunb.2022.808578. eCollection 2022.ABSTRACTThe role of lipo-chitooligosaccharides (LCOs) as signaling molecules that mediate the establishment of symbiotic relationships between fungi and plants is being redefined. New evidence suggests that the production of these molecular signals may be more of a common trait in fungi than what was previously thought. LCOs affect different aspects of growth and development in fungi. For the ectomycorrhizal forming fungi, Laccaria bicolor, the production and effects of LCOs have always been studied with a symbiotic plant partner; however, there is still no scientific evidence describing the effects that these molecules have on this organism. Here, we explored the physiological, molecular, and metabolomic changes in L. bicolor when grown in the presence of exogenous sulfated and non-sulfated LCOs, as well as the chitooligomers, chitotetraose (CO4), and chitooctaose (CO8). Physiological data from 21 days post-induction showed reduced fungal growth in response to CO and LCO treatments compared to solvent controls. The underlying molecular changes were interrogated by proteomics, which revealed substantial alterations to biological processes related to growth and development. Moreover, metabolite data showed that LCOs and COs caused a downregulation of organic acids, sugars, and fatty acids. At the same time, exposure to LCOs resulted in the overproduction of lactic acid in L. bicolor. Altogether, these results suggest that these signals might be fungistatic compounds and contribute to current research efforts investigating the emerging impacts of these molecules on fungal growth and development.PMID:37746234 | PMC:PMC10512320 | DOI:10.3389/ffunb.2022.808578

Front Fungal Biol. 2022 Sep 27;3:998361. doi: 10.3389/ffunb.2022.998361. eCollection 2022.ABSTRACTTrichoderma reesei and Aspergillus niger are efficient biological platforms for the production of various industrial products, including cellulases and organic acids. Nevertheless, despite the extensive research on these fungi, integrated analyses of omics-driven approaches are still missing. In this study, the intracellular metabolic profile of T. reesei RUT-C30 and A. niger N402 strains grown on glucose, lactose, carboxymethylcellulose (CMC), and steam-exploded sugarcane bagasse (SEB) as carbon sources for 48 h was analysed by proton nuclear magnetic resonance. The aim was to verify the changes in the primary metabolism triggered by these substrates and use transcriptomics data from the literature to better understand the dynamics of the observed alterations. Glucose and CMC induced higher fungal growth whereas fungi grown on lactose showed the lowest dry weight. Metabolic profile analysis revealed that mannitol, trehalose, glutamate, glutamine, and alanine were the most abundant metabolites in both fungi regardless of the carbon source. These metabolites are of particular interest for the mobilization of carbon and nitrogen, and stress tolerance inside the cell. Their concomitant presence indicates conserved mechanisms adopted by both fungi to assimilate carbon sources of different levels of recalcitrance. Moreover, the higher levels of galactose intermediates in T. reesei suggest its better adaptation in lactose, whereas glycolate and malate in CMC might indicate activation of the glyoxylate shunt. Glycerol and 4-aminobutyrate accumulated in A. niger grown on CMC and lactose, suggesting their relevant role in these carbon sources. In SEB, a lower quantity and diversity of metabolites were identified compared to the other carbon sources, and the metabolic changes and higher xylanase and pNPGase activities indicated a better utilization of bagasse by A. niger. Transcriptomic analysis supported the observed metabolic changes and pathways identified in this work. Taken together, we have advanced the knowledge about how fungal primary metabolism is affected by different carbon sources, and have drawn attention to metabolites still unexplored. These findings might ultimately be considered for developing more robust and efficient microbial factories.PMID:37746225 | PMC:PMC10512294 | DOI:10.3389/ffunb.2022.998361

Front Fungal Biol. 2023 Aug 1;4:1141963. doi: 10.3389/ffunb.2023.1141963. eCollection 2023.ABSTRACTConsidering our growing population and our continuous degradation of soil environments, understanding the fundamental ecology of soil biota and plant microbiomes will be imperative to sustaining soil systems. Arbuscular mycorrhizal (AM) fungi extend their hyphae beyond plant root zones, creating microhabitats with bacterial symbionts for nutrient acquisition through a tripartite symbiotic relationship along with plants. Nonetheless, it is unclear what drives these AM fungal-bacterial relationships and how AM fungal functional traits contribute to these relationships. By delving into the literature, we look at the drivers and complexity behind AM fungal-bacterial relationships, describe the shift needed in AM fungal research towards the inclusion of interdisciplinary tools, and discuss the utilization of bacterial datasets to provide contextual evidence behind these complex relationships, bringing insights and new hypotheses to AM fungal functional traits. From this synthesis, we gather that interdependent microbial relationships are at the foundation of understanding microbiome functionality and deciphering microbial functional traits. We suggest using pattern-based inference tools along with machine learning to elucidate AM fungal-bacterial relationship trends, along with the utilization of synthetic communities, functional gene analyses, and metabolomics to understand how AM fungal and bacterial communities facilitate communication for the survival of host plant communities. These suggestions could result in improving microbial inocula and products, as well as a better understanding of complex relationships in terrestrial ecosystems that contribute to plant-soil feedbacks.PMID:37746131 | PMC:PMC10512368 | DOI:10.3389/ffunb.2023.1141963

Front Plant Sci. 2023 Sep 8;14:1192151. doi: 10.3389/fpls.2023.1192151. eCollection 2023.ABSTRACTMagnesium (Mg) is one of the essential elements for the growth of tea trees. In this study, we investigated changes in metabolites, photosynthetic fluorescence parameters and quality indexes of tea leaves under different concentrations of magnesium treatment, and the results showed that there were no significant differences in the quantity and total content of metabolites in tea leaves under different Mg concentrations. The results of volcano map analysis showed that the content of 235 metabolites in tea leaves showed an increasing trend and the content of 243 metabolites showed a decreasing trend with the increase of Mg concentration. The results of the combined analysis of the OPLS-DA model and bubble map showed that 45 characteristic metabolites were screened at different concentrations of Mg. Among these, the content of 24 characteristic metabolites showed an increasing trend and 21 characteristic metabolites showed a decreasing trend with the increase of Mg concentrations. The results of KEEG pathway enrichment showed that 24 characteristic metabolites with a upward trend were significantly enriched in saccharides metabolism, nucleic acid metabolism and vitamin metabolism, while the 21 characteristic metabolites with a downward trend were enriched in the synthesis of plant secondary metabolites, phenylpropanoid biosynthesis, biosynthesis of terpenoids, synthesis and metabolism of alkaloids, and synthesis and metabolism of amino acids. It can be inferred that Mg regulation was beneficial to enhance the photosynthetic capacity of tea trees, improve the accumulation and metabolism of carbohydrate substances in tea trees, and thus promoted the growth of tea trees, but was not conducive to the synthesis of secondary metabolites and amino acids related to tea quality. The results of photosynthetic fluorescence parameters and quality indexes of the tea tree confirmed the conclusion predicted by metabolomics. This study provided a reference for regulating of the growth and quality of tea trees with Mg fertilizer in tea plantations.PMID:37746019 | PMC:PMC10514580 | DOI:10.3389/fpls.2023.1192151

Front Plant Sci. 2023 Sep 8;14:1195389. doi: 10.3389/fpls.2023.1195389. eCollection 2023.ABSTRACTWater lilies are popular ornamental cut-flowers with significant economic and cultural value. However, stem bending affects the preservation of cut-flowers during their vase life. To gain further insights into the molecular mechanisms of stem bending, transcriptome profiling, hormone measurement, and morphological analysis were performed using the stems of the 'Blue Bird' water lily. Transcriptome analysis revealed that 607 differentially expressed genes (DEGs) were associated with the dorsal and ventral stems of the water lily, of which 247 were up-regulated and 360 were down-regulated. Significant differences in genes associated with plant hormones, calcium ions, glucose metabolism, and photosynthesis pathways genes involved in the dorsal and ventral areas of the curved stem. In particular, DEGs were associated with the hormone synthesis, gravity response, starch granules, Ca2+ ions, and photosynthesis. The results of qRT-PCR were consistent with that of the transcriptome sequence analysis. A total of 12 hormones were detected, of which abscisic acid, indole-3-carboxaldehyde, indole-3-carboxaldehyde and jasmonic acid were significantly differentially expressed in the dorsal and ventral stems, and were significantly higher in the dorsal stem than in the ventral stem. The cell morphology in the dorsal and ventral areas of the curved stem clearly changed during vase life. The direction of starch granule settlement was consistent with the bending direction of the water lily stem, as well as the direction of gravity. In conclusion, stem bending in water lily cut-flowers is regulated by multiple factors and genes. This study provides an important theoretical basis for understanding the complex regulatory mechanism of water lily stem bending.PMID:37746018 | PMC:PMC10515221 | DOI:10.3389/fpls.2023.1195389

Front Plant Sci. 2023 Sep 8;14:1195673. doi: 10.3389/fpls.2023.1195673. eCollection 2023.ABSTRACTThe valorisation and conservation of plant genetic resources (PGRs) and wild fruit PGRs are critical to ensure the maintenance of genetic and cultural heritage and to promote new perspectives on resource use. New strategies to characterize PGRs are needed, and the omics approach can provide information that is still largely unknown. The Strawberry tree (Arbutus unedo L.) is an underutilized, drought and fire-resistant species distributed in the Mediterranean area and its berries have large ethnobotanical use. Although their phenolic profile and antioxidant capacity are known, they are not well characterised, particularly from a proteomic perspective. The aim of this work is the characterisation of two ecotypes of A. unedo (Campania and Sicily) from a molecular viewpoint to valorise and encourage the preservation of this wild fruit. Samples were collected from two different geographical areas to assess whether different geographical conditions could influence the characteristics of leaves and fruits at the three stages of ripening (green, veraison, red). Proteomic analysis identified 904 proteins, of which 122 showed significance along the ripening. Some of these differentially abundant proteins, such as chalcone synthase, show a marked increase during ripening. The protein functional classes with the highest representation are involved in protein and amino acid metabolism, glycolysis and in secondary metabolism. From a proteomic perspective, there are no differences between the fruits from the two regions compared by the ripening stage. However, the pedoclimatic metabolic imprinting allowed the observation of good diversity in the metabolomic profiles between the two ecotypes, especially for anthocyanins, 4 times more abundant in the Sicilian veraisoned fruit than in the Campania one, and catechins, with double the abundance in the Campania ecotype compared to the Sicilian ecotype in the green phase, but more abundant (3x) in the Sicilian veraisoned fruit. Phenolic compounds show a 20% greater abundance in the Campania green arbutus fruit than in the Sicilian one, values that then equalise as ripening progresses. Multi-omic characterisation enhanced the knowledge on a wild fruit plant species which shows specific adaptations and responses to the environment to be considered when addressing the issue of local agrobiodiversity.PMID:37745992 | PMC:PMC10514896 | DOI:10.3389/fpls.2023.1195673

Front Plant Sci. 2023 Sep 7;14:1281889. doi: 10.3389/fpls.2023.1281889. eCollection 2023.NO ABSTRACTPMID:37745987 | PMC:PMC10513781 | DOI:10.3389/fpls.2023.1281889

Front Genet. 2023 Sep 6;14:1219335. doi: 10.3389/fgene.2023.1219335. eCollection 2023.ABSTRACTIntroduction: Yanling Yinbiancha, a cultivar of Camellia sinensis (L.) O. Kuntze, is an evergreen woody perennial with characteristic albino leaves. A mutant variant with green leaves on branches has been recently identified. The molecular mechanisms underlying this color variation remain unknown. Methods: We aimed to utilize omics tools to decipher the molecular basis for this color variation, with the ultimate goal of enhancing existing germplasm and utilizing it in future breeding programs. Results and discussion: Albinotic leaves exhibited significant chloroplast degeneration and reduced carotenoid accumulation. Transcriptomic and metabolomic analysis of the two variants revealed 1,412 differentially expressed genes and 127 differentially accumulated metabolites (DAMs). Enrichment analysis for DEGs suggested significant enrichment of pathways involved in the biosynthesis of anthocyanins, porphyrin, chlorophyll, and carotenoids. To further narrow down the causal variation for albinotic leaves, we performed a conjoint analysis of metabolome and transcriptome and identified putative candidate genes responsible for albinism in C. sinensis leaves. 12, 7, and 28 DEGs were significantly associated with photosynthesis, porphyrin/chlorophyll metabolism, and flavonoid metabolism, respectively. Chlorophyllase 2, Chlorophyll a-Binding Protein 4A, Chlorophyll a-Binding Protein 24, Stay Green Regulator, Photosystem II Cytochrome b559 subunit beta along with transcription factors AP2, bZIP, MYB, and WRKY were identified as a potential regulator of albinism in Yanling Yinbiancha. Moreover, we identified Anthocyanidin reductase and Arabidopsis Response Regulator 1 as DEGs influencing flavonoid accumulation in albino leaves. Identification of genes related to albinism in C. sinensis may facilitate genetic modification or development of molecular markers, potentially enhancing cultivation efficiency and expanding the germplasm for utilization in breeding programs.PMID:37745858 | PMC:PMC10516542 | DOI:10.3389/fgene.2023.1219335

Front Endocrinol (Lausanne). 2023 Sep 8;14:1255889. doi: 10.3389/fendo.2023.1255889. eCollection 2023.ABSTRACTBACKGROUND: Senescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR).METHODS: The genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design.RESULTS: GNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway.CONCLUSION: HannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.PMID:37745724 | PMC:PMC10514473 | DOI:10.3389/fendo.2023.1255889

Front Endocrinol (Lausanne). 2023 Sep 6;14:1211015. doi: 10.3389/fendo.2023.1211015. eCollection 2023.ABSTRACTAIMS/HYPOTHESIS: Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).METHODS: Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.RESULTS: We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.CONCLUSION/INTERPRETATION: Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.PMID:37745723 | PMC:PMC10516565 | DOI:10.3389/fendo.2023.1211015

bioRxiv. 2023 Sep 15:2023.09.12.557189. doi: 10.1101/2023.09.12.557189. Preprint.ABSTRACTMass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics, and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive and systematic comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address this pressing need, we developed omicsMIC (mass spectrometrybased omics with Missing values Imputation methods Comparison platform), an interactive platform that provides researchers with a versatile framework to simulate and evaluate the performance of 28 diverse imputation methods. omicsMIC offers a nuanced perspective, acknowledging the inherent heterogeneity in biological data and the unique attributes of each dataset. Our platform empowers researchers to make data-driven decisions in imputation method selection based on real-time visualizations of the outcomes associated with different imputation strategies. The comprehensive benchmarking and versatility of omicsMIC make it a valuable tool for the scientific community engaged in mass spectrometry-based omics research. OmicsMIC is freely available at https://github.com/WQLin8/omicsMIC .PMID:37745599 | PMC:PMC10515867 | DOI:10.1101/2023.09.12.557189