PubMed

J Diabetes Metab Disord. 2023 Jul 14;22(2):985-994. doi: 10.1007/s40200-023-01256-8. eCollection 2023 Dec.ABSTRACTOBJECTIVES: The exact underlying mechanism of developing diabetes-related cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is not clear. Metabolomics can provide a platform enabling the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The aim of this review is to summarize the available evidence on the relationship between metabolomics and cardiovascular diseases in patients with diabetes.METHODS: The literature was searched to find out studies that have investigated the relationship between the alteration of specific metabolites and cardiovascular diseases in patients with diabetes.RESULTS: Evidence proposed that changes in the metabolism of certain amino acids, lipids, and carbohydrates, independent of traditional CVD risk factors, are associated with increased CVD risk.CONCLUSIONS: Metabolomics can provide a platform to enable the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The association of the alteration in specific metabolites with CVD may be considered in the investigations for the development of new therapeutic targets for the prevention of CVD in patients with diabetes mellitus.PMID:37975080 | PMC:PMC10638133 | DOI:10.1007/s40200-023-01256-8

BMC Microbiol. 2023 Nov 16;23(1):343. doi: 10.1186/s12866-023-03085-4.ABSTRACTEndophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1-26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.PMID:37974074 | DOI:10.1186/s12866-023-03085-4

Nat Commun. 2023 Nov 16;14(1):7427. doi: 10.1038/s41467-023-43304-0.ABSTRACTAs one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomic analysis of lungs from JHU083-treated Mtb-infected mice reveals citrulline accumulation, suggesting elevated nitric oxide (NO) synthesis, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. JHU083-treated macrophages also produce more NO potentiating their antibacterial activity. When tested in an immunocompromised mouse model of Mtb infection, JHU083 loses its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.PMID:37973991 | DOI:10.1038/s41467-023-43304-0

Nat Metab. 2023 Nov 16. doi: 10.1038/s42255-023-00916-6. Online ahead of print.ABSTRACTTransient reprogramming by the expression of OCT4, SOX2, KLF4 and MYC (OSKM) is a therapeutic strategy for tissue regeneration and rejuvenation, but little is known about its metabolic requirements. Here we show that OSKM reprogramming in mice causes a global depletion of vitamin B12 and molecular hallmarks of methionine starvation. Supplementation with vitamin B12 increases the efficiency of reprogramming both in mice and in cultured cells, the latter indicating a cell-intrinsic effect. We show that the epigenetic mark H3K36me3, which prevents illegitimate initiation of transcription outside promoters (cryptic transcription), is sensitive to vitamin B12 levels, providing evidence for a link between B12 levels, H3K36 methylation, transcriptional fidelity and efficient reprogramming. Vitamin B12 supplementation also accelerates tissue repair in a model of ulcerative colitis. We conclude that vitamin B12, through its key role in one-carbon metabolism and epigenetic dynamics, improves the efficiency of in vivo reprogramming and tissue repair.PMID:37973897 | DOI:10.1038/s42255-023-00916-6

Nat Chem Biol. 2023 Nov 16. doi: 10.1038/s41589-023-01474-4. Online ahead of print.ABSTRACTProteins and RNA can phase separate from the aqueous cellular environment to form subcellular compartments called condensates. This process results in a protein-RNA mixture that is chemically different from the surrounding aqueous phase. Here, we use mass spectrometry to characterize the metabolomes of condensates. To test this, we prepared mixtures of phase-separated proteins and extracts of cellular metabolites and identified metabolites enriched in the condensate phase. Among the most condensate-enriched metabolites were phospholipids, due primarily to the hydrophobicity of their fatty acyl moieties. We found that phospholipids can alter the number and size of phase-separated condensates and in some cases alter their morphology. Finally, we found that phospholipids partition into a diverse set of endogenous condensates as well as artificial condensates expressed in cells. Overall, these data show that many condensates are protein-RNA-lipid mixtures with chemical microenvironments that are ideally suited to facilitate phospholipid biology and signaling.PMID:37973889 | DOI:10.1038/s41589-023-01474-4

Nat Microbiol. 2023 Nov 16. doi: 10.1038/s41564-023-01518-4. Online ahead of print.ABSTRACTDevelopment of microbial communities is a complex multiscale phenomenon with wide-ranging biomedical and ecological implications. How biological and physical processes determine emergent spatial structures in microbial communities remains poorly understood due to a lack of simultaneous measurements of gene expression and cellular behaviour in space and time. Here we combined live-cell microscopy with a robotic arm for spatiotemporal sampling, which enabled us to simultaneously acquire phenotypic imaging data and spatiotemporal transcriptomes during Bacillus subtilis swarm development. Quantitative characterization of the spatiotemporal gene expression patterns revealed correlations with cellular and collective properties, and phenotypic subpopulations. By integrating these data with spatiotemporal metabolome measurements, we discovered a spatiotemporal cross-feeding mechanism fuelling swarm development: during their migration, earlier generations deposit metabolites which are consumed by later generations that swarm across the same location. These results highlight the importance of spatiotemporal effects during the emergence of phenotypic subpopulations and their interactions in bacterial communities.PMID:37973866 | DOI:10.1038/s41564-023-01518-4

Genome Res. 2023 Nov 16. doi: 10.1101/gr.278144.123. Online ahead of print.ABSTRACTOrgans and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, such as the transcriptome and metabolome. However, we lack a conceptual framework to understand why some components age faster than others. Just as demographic models explain why aging evolves, here we test the hypothesis that demographic differences among cell types, determined by cell-specific differences in turnover rate, can explain why the transcriptome shows signs of aging in some cell types but not others. Through analysis of mouse single-cell transcriptome data across diverse tissues and ages, we find that cellular age explains a large proportion of the variation in the age-related increase in transcriptome variance. We further show that long-lived cells are characterized by relatively high expression of genes associated with proteostasis and that the transcriptome of long-lived cells shows greater evolutionary constraint than short-lived cells. In contrast, in short-lived cell types, the transcriptome is enriched for genes associated with DNA repair. Based on these observations, we develop a novel heuristic model that explains how and why aging rates differ among cell types.PMID:37973195 | DOI:10.1101/gr.278144.123

J Ethnopharmacol. 2023 Nov 14:117408. doi: 10.1016/j.jep.2023.117408. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po Decoction (ZZHPD), as a representative traditional Chinese medicine (TCM) formula for the treatment of depression, has frequently triggered hepatorenal toxicity in recent years. However, its toxic effect, material basis, and underlying mechanisms have not been fully elucidated.AIM OF THE STUDY: To explore the hepatorenal toxicity-material basis-quality markers (Q-markers) and multiple mechanisms of ZZHPD.MATERIALS AND METHODS: ZZHPD-induced rat model of toxicity was evaluated by behavioral indicators, biochemical parameters, histopathological sections. Then, UHPLC-Q-Exactive Orbitrap-MS combined with multivariate data analysis was utilized to identify the endogenous differential metabolites and the prototype components of ZZHPD in the plasma. A comprehensive strategy integrating in-house library, diagnostic ions, Compound Discover software and network databases was constructed to identify the chemical constituents of ZZHPD. Additionally, the differential absorbed components of ZZHPD were screened out based on the spectrum-effect relationship (toxic state and normal state), feature extraction of exogenous components and variable influence on projection (VIP). Further, Chinmedomics and network pharmacology oriented by differential absorbed components were performed to predict toxicity-related Q-markers and core targets, as well as relevant pathways. Finally, the binding ability between the components and targets was predicted using molecular docking, and the mRNA expression of core target genes was determined by real-time qPCR experiment.RESULTS: ZZHPD exerted significant hepatotoxicity and nephrotoxicity in rats accompanied by body weight loss, abnormal biochemical indicators, and pathologic characteristics with mild inflammation and cell damage. The results of plasma metabolomics indicated that 22 differential metabolites interfered by ZZHPD mainly involved in primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism and biosynthesis, sphingolipid metabolism, pyrimidine and purine metabolism. Firstly, 106 chemical substances of ZZHPD were identified, 44 of them were absorbed into the blood, mainly including 7 iridoid glycosides, 15 flavonoids, 5 lignans, and others. Then, the correlation analysis results suggested that 12 of 19 differential absorbed constituents were highly correlated with 22 differential metabolites and were recognized as potential Q-markers. Finally, 9 toxicity-related Q-markers were predicted and confirmed with better binding ability to 5 core targets (PTGS2, CASP3, TNF, PPARG, HMOX1), including 3 flavonoids (naringin, hesperidin and neohesperidin), 2 iridoid glycosides (geniposide and genipin-1-β-d-gentiobioside), 2 lignans (honokiol and magnolol), organic acid (chlorogenic acid), and crocin (crocetin). The real-time qPCR results showed that the mRNA levels of CASP3, TNF-α and PPARG significantly increased in the damaged liver. Combining metabolomics and network pharmacology results, the multiple mechanisms of toxicity might involve in oxidative damage, inflammation, and apoptosis pathways.CONCLUSION: Taken together, the toxicity-related Q-markers of ZZHPD screened for the first time in this work were reliable, and the holistic intervention for hepatorenal toxicity further revealed the multi-component, multi-target and multi-pathway features in TCM. The integrated approach provides a novel perspective for the discovery of toxicity/efficacy-related substances and mechanistic studies in TCM.PMID:37972910 | DOI:10.1016/j.jep.2023.117408

Pharmacol Res. 2023 Nov 14:106994. doi: 10.1016/j.phrs.2023.106994. Online ahead of print.ABSTRACTThe functional interdependencies between the molecular components of a biological process demands for a network medicine platform that integrates systems biology and network science, to explore the interactions among biological components in health and disease. Access to large-scale omics datasets (genomics, transcriptomics, proteomics, metabolomics, metagenomics, phenomics, etc.) has significantly advanced our opportunity along this direction. Studies utilizing these techniques have begun to provide us with a deeper understanding of how the interaction between the intestinal microbes and their host affects the cardiovascular system in health and disease. Within the framework of a multiomics network approach, we highlight here how tryptophan metabolism may orchestrate the host-microbes interaction in cardiovascular diseases and the implications for precision medicine and therapeutics, including nutritional interventions.PMID:37972721 | DOI:10.1016/j.phrs.2023.106994

Ticks Tick Borne Dis. 2023 Nov 14;15(1):102279. doi: 10.1016/j.ttbdis.2023.102279. Online ahead of print.ABSTRACTGuinea pigs repeatedly exposed to Ixodes scapularis develop acquired resistance to the ticks (ATR). The molecular mechanisms of ATR have not been fully elucidated, and partially involves immune responses to proteins in tick saliva. In this study, we examined the metabolome of sera of guinea pigs during the development of ATR. Induction of components of the tyrosine metabolic pathway, including hydroxyphenyllactic acid (HPLA), were associated with ATR. We therefore administered HPLA to mice, an animal that does not develop ATR, and exposed the animals to I. scapularis. We also administered nitisinone, a known inhibitor of tyrosine degradation, to another group of mice. The mortality of I. scapularis that fed on mice given HPLA or nitisinone was 26 % and 72 % respectively, compared with 2 % mortality among ticks that fed on control animals. These data indicate that tick bites alter the guinea pig metabolome, and that the tyrosine metabolism pathway can potentially be targeted for I. scapularis control.PMID:37972499 | DOI:10.1016/j.ttbdis.2023.102279

Phytomedicine. 2023 Nov 6;123:155190. doi: 10.1016/j.phymed.2023.155190. Online ahead of print.ABSTRACTBACKGROUND: Acute lung injury (ALI) is distinguished by rapid and severe respiratory distress and prolonged hypoxemia. A traditional Chinese medicine (TCM), known as the Fuzhengjiedu formula (FZJDF), has been shown to have anti-inflammatory benefits in both clinical and experimental studies. The precise underlying processes, nevertheless, are yet unclear.PURPOSE: This study sought to enlighten the protective mechanism of FZJDF in ALI through the standpoint of the gut-lung crosstalk.METHODS: The impact of FZJDF on lipopolysaccharide (LPS)-induced ALI murine model were investigated, and the lung injury score, serum interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) expression were measured to confirm its anti-inflammatory effects. Additionally, gut microbiota analysis and serum and fecal samples metabolomics were performed using metagenomic sequencing and high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, respectively.RESULTS: FZJDF significantly induced histopathological changes caused by LPS-induced ALI as well as downregulated the serum concentration of IL-1β and TNF-α. Furthermore, FZJDF had an effect in gut microbiota disturbances, and linear discriminant effect size analysis identified signal transduction, cell motility, and amino acid metabolism as the potential mechanisms of action in the FZJDF-treated group. Several metabolites in the LPS and FZJDF groups were distinguished by untargeted metabolomic analysis. Correlations were observed between the relative abundance of microbiota and metabolic products. Comprehensive network analysis revealed connections among lung damage, gut microbes, and metabolites. The expression of glycine, serine, glutamate, cysteine, and methionine in the lung and colon tissues was dysregulated in LPS-induced ALI, and FZJDF reversed these trends.CONCLUSION: This study revealed that FZJDF considerably protected against LPS-induced ALI in mice by regulating amino acid metabolism via the gut-microbiota-lung axis and offered thorough and in-depth knowledge of the multi-system linkages of systemic illnesses.PMID:37972468 | DOI:10.1016/j.phymed.2023.155190

J Clin Invest. 2023 Nov 16:e170397. doi: 10.1172/JCI170397. Online ahead of print.ABSTRACTWhile the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, H2O2 specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma-lyase (CTH), which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.PMID:37971886 | DOI:10.1172/JCI170397

Ann Hematol. 2023 Nov 16. doi: 10.1007/s00277-023-05533-7. Online ahead of print.ABSTRACTOBJECTIVES: This study aimed to investigate the incidence rate and spectrum of gene mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Huizhou city of southern China to provide a scientific basis for disease prevention and control in the area.METHODS: From March 2003 to December 2022, newborn screening for G6PD enzyme activity was carried out in Huizhou city using the fluorescence quantitative method. Infants who tested positive during the initial screening were diagnosed using the nitroblue tetrazolium ratio method, while a subset of infants received further gene mutation analysis using the multicolor probe melting curve analysis method.RESULTS: A total of 1,291,274 newborns were screened and the screening rate has increased from 20.39% to almost 100%. In the 20-year period, 57,217 (4.43%) infants testing positive during the initial screening. Out of these infants, 49,779 (87%) were recalled for confirmatory testing. G6PD deficiency was confirmed in 39,261 of the recalled infants, indicating a positive predictive value of 78.87%. The estimated incidence rate of G6PD deficiency in the region was 3.49%, which was significantly higher than the average incidence rate of 2.1% in southern China. On the other hand, seven pathogenic G6PD variants were identified in the analysis of the 99 diagnosed infants with the most common being c.1388 G > A (48.5%), followed by c.95 A > G (19.2%), c.1376 G > T (15.2%), c.871 G > A (9.1%), c.1360 C > T (3.0%), c.392 G > T (3.0%), and c.487 G > A (1.0%).CONCLUSION: The incidence of G6PD deficiency in newborns in the Huizhou city was higher than the southern China average level, while the types and frequencies of gene mutations were found to vary slightly from other regions. Our findings suggested that free government screening and nearby diagnosis strategies could reduce the incidence of G6PD deficiency in the area.PMID:37971548 | DOI:10.1007/s00277-023-05533-7

Nucleic Acids Res. 2023 Nov 16:gkad1045. doi: 10.1093/nar/gkad1045. Online ahead of print.ABSTRACTMetaboLights is a global database for metabolomics studies including the raw experimental data and the associated metadata. The database is cross-species and cross-technique and covers metabolite structures and their reference spectra as well as their biological roles and locations where available. MetaboLights is the recommended metabolomics repository for a number of leading journals and ELIXIR, the European infrastructure for life science information. In this article, we describe the continued growth and diversity of submissions and the significant developments in recent years. In particular, we highlight MetaboLights Labs, our new Galaxy Project instance with repository-scale standardized workflows, and how data public on MetaboLights are being reused by the community. Metabolomics resources and data are available under the EMBL-EBI's Terms of Use at https://www.ebi.ac.uk/metabolights and under Apache 2.0 at https://github.com/EBI-Metabolights.PMID:37971328 | DOI:10.1093/nar/gkad1045

Nucleic Acids Res. 2023 Nov 16:gkad1046. doi: 10.1093/nar/gkad1046. Online ahead of print.ABSTRACTThe Bioinformation and DNA Data Bank of Japan (DDBJ) Center (https://www.ddbj.nig.ac.jp) provides database archives that cover a wide range of fields in life sciences. As a founding member of the International Nucleotide Sequence Database Collaboration (INSDC), DDBJ accepts and distributes nucleotide sequence data as well as their study and sample information along with the National Center for Biotechnology Information in the United States and the European Bioinformatics Institute (EBI). Besides INSDC databases, the DDBJ Center provides databases for functional genomics (GEA: Genomic Expression Archive), metabolomics (MetaboBank) and human genetic and phenotypic data (JGA: Japanese Genotype-phenotype Archive). These database systems have been built on the National Institute of Genetics (NIG) supercomputer, which is also open for domestic life science researchers to analyze large-scale sequence data. This paper reports recent updates on the archival databases and the services of the DDBJ Center, highlighting the newly redesigned MetaboBank. MetaboBank uses BioProject and BioSample in its metadata description making it suitable for multi-omics large studies. Its collaboration with MetaboLights at EBI brings synergy in locating and reusing public data.PMID:37971299 | DOI:10.1093/nar/gkad1046

Microbiol Spectr. 2023 Nov 16:e0331223. doi: 10.1128/spectrum.03312-23. Online ahead of print.ABSTRACTHeat stress is one of the main causes of economic losses in the dairy industry worldwide; however, the mechanisms associated with the metabolic and microbial changes in heat stress remain unclear. Here, we characterized both the changes in metabolites, rumen microbial communities, and their functional potential indices derived from rumen fluid and serum samples from cows at different growth stages and under different climates. This study highlights that the rumen microbe may be involved in the regulation of lipid metabolism by modulating the fatty acyl metabolites. Under heat stress, the changes in the metabolic status of growing heifers, heifers, and lactating cows were closely related to arachidonic acid metabolism, fatty acid biosynthesis, and energy metabolism. Moreover, this study provides new markers for further research to understand the effects of heat stress on the physiological metabolism of Holstein cows and the time-dependent changes associated with growth stages.PMID:37971264 | DOI:10.1128/spectrum.03312-23

J Proteome Res. 2023 Nov 16. doi: 10.1021/acs.jproteome.3c00548. Online ahead of print.ABSTRACTProbiotics are live microorganisms that confer health benefits when administered in adequate amounts. They are used to promote gut health and alleviate various disorders. Recently, there has been an increasing interest in the potential effects of probiotics on human physiology. In the presented study, the effects of probiotic treatment on the metabolic profiles of human urine and serum using a nuclear magnetic resonance (NMR)-based metabonomic approach were investigated. Twenty-one healthy volunteers were enrolled in the study, and they received two different dosages of probiotics for 8 weeks. During the study, urine and serum samples were collected from volunteers before and during probiotic supplementation. The results showed that probiotics had a significant impact on the urinary and serum metabolic profiles without altering their phenotypes. This study demonstrated the effects of probiotics in terms of variations of metabolite levels resulting also from the different probiotic posology. Overall, the results suggest that probiotic administration may affect both urine and serum metabolomes, although more research is needed to understand the mechanisms and clinical implications of these effects. NMR-based metabonomic analysis of biofluids is a powerful tool for monitoring host-gut microflora dynamic interaction as well as for assessing the individual response to probiotic treatment.PMID:37970754 | DOI:10.1021/acs.jproteome.3c00548

Explor Target Antitumor Ther. 2023;4(5):812-849. doi: 10.37349/etat.2023.00170. Epub 2023 Sep 28.ABSTRACTFrom attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, to re-searching the age-old theory of intrinsic metabolic shift of cancers (Warburg's glycolysis), the quest for a precise panacea for mainly the metastatic cancers, remains incessant. This review delineates the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway driven intricate oncogenic cues, budding from the metabolic (glycolytic) reliance of tumour cells, branching into metastatic emergence of malignancies. Strong AGE-RAGE concomitance in metastasis, chemo-resistance and cancer resurgence adversely incite disease progression and patient mortality. At the conjunction of metabolic and metastatic shift of cancers, are the "glycolytically" generated AGEs and AGE-activated RAGE, instigating aberrant molecular pathways, culminating in aggressive malignancies. AGEs as by-products of metabolic insurgence, modify the metabolome, epigenome and microbiome, besides coercing the inter-, intra- and extra-cellular micro-milieu conducive for oncogenic events like epithelial-mesenchymal transition (EMT). AGE-RAGE synergistically elicit ATP surge for surplus energy, autophagy for apoptotic evasion and chemo-resistance, insulin-like growth factor 1 (IGF-1) for meta-inflammation and angiogenesis, high mobility group box-1 (HMGB1) for immune tolerance, S100 proteins for metastasis, and p53 protein attenuation for tumour suppression. AGEs are pronouncedly reported in invasive forms of breast, prostate, colon and pancreatic cancers, higher in patients with cancer than healthy counterparts, and higher in advanced stage than localized phase. Hence, the investigation of person-specific presence of AGEs, soluble RAGE and AGE-activated RAGE can be advocated as impending bio-markers for diagnostic, prognostic and therapeutic purposes, to predict cancer risk in patients with diabetes, obesity, metabolic syndrome as well as general population, to monitor prognosis and metastasis in patients with cancer, and to reckon complications in cancer survivors. Furthermore, clinical reports of exogenous (dietary) and endogenous (internally formed) AGEs in cancer patients, and contemporary clinical trials involving AGE-RAGE axis in cancer are underlined with theranostic implications.PMID:37970208 | PMC:PMC10645465 | DOI:10.37349/etat.2023.00170

Chin J Cancer Res. 2023 Oct 30;35(5):550-562. doi: 10.21147/j.issn.1000-9604.2023.05.11.ABSTRACTOBJECTIVE: As an important part of metabolomics analysis, untargeted metabolomics has become a powerful tool in the study of tumor mechanisms and the discovery of metabolic markers with high-throughput spectrometric data which also poses great challenges to data analysis, from the extraction of raw data to the identification of differential metabolites. To date, a large number of analytical tools and processes have been developed and constructed to serve untargeted metabolomics research. The different selection of analytical tools and parameter settings lead to varied results of untargeted metabolomics data. Our goal is to establish an easily operated platform and obtain a repeatable analysis result.METHODS: We used the R language basic environment to construct the preprocessing system of the original data and the LAMP (Linux+Apache+MySQL+PHP) architecture to build a cloud mass spectrum data analysis system.RESULTS: An open-source analysis software for untargeted metabolomics data (openNAU) was constructed. It includes the extraction of raw mass data and quality control for the identification of differential metabolic ion peaks. A reference metabolomics database based on public databases was also constructed.CONCLUSIONS: A complete analysis system platform for untargeted metabolomics was established. This platform provides a complete template interface for the addition and updating of the analysis process, so we can finish complex analyses of untargeted metabolomics with simple human-computer interactions. The source code can be downloaded from https://github.com/zjuRong/openNAU.PMID:37969962 | PMC:PMC10643343 | DOI:10.21147/j.issn.1000-9604.2023.05.11

J Biomol Tech. 2023 Aug 7;34(3):3fc1f5fe.a058bad4. doi: 10.7171/3fc1f5fe.a058bad4. eCollection 2023 Sep 30.ABSTRACTMetaproteomics research using mass spectrometry data has emerged as a powerful strategy to understand the mechanisms underlying microbiome dynamics and the interaction of microbiomes with their immediate environment. Recent advances in sample preparation, data acquisition, and bioinformatics workflows have greatly contributed to progress in this field. In 2020, the Association of Biomolecular Research Facilities Proteome Informatics Research Group launched a collaborative study to assess the bioinformatics options available for metaproteomics research. The study was conducted in 2 phases. In the first phase, participants were provided with mass spectrometry data files and were asked to identify the taxonomic composition and relative taxa abundances in the samples without supplying any protein sequence databases. The most challenging question asked of the participants was to postulate the nature of any biological phenomena that may have taken place in the samples, such as interactions among taxonomic species. In the second phase, participants were provided a protein sequence database composed of the species present in the sample and were asked to answer the same set of questions as for phase 1. In this report, we summarize the data processing methods and tools used by participants, including database searching and software tools used for taxonomic and functional analysis. This study provides insights into the status of metaproteomics bioinformatics in participating laboratories and core facilities.PMID:37969874 | PMC:PMC10644979 | DOI:10.7171/3fc1f5fe.a058bad4