PubMed

J Imaging. 2023 Jul 25;9(8):149. doi: 10.3390/jimaging9080149.ABSTRACTPancreatic carcinoma (Ca Pancreas) is the third leading cause of cancer-related deaths in the world. The malignancies of the pancreas can be diagnosed with the help of various imaging modalities. An endoscopic ultrasound with a tissue biopsy is so far considered to be the gold standard in terms of the detection of Ca Pancreas, especially for lesions <2 mm. However, other methods, like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), are also conventionally used. Moreover, newer techniques, like proteomics, radiomics, metabolomics, and artificial intelligence (AI), are slowly being introduced for diagnosing pancreatic cancer. Regardless, it is still a challenge to diagnose pancreatic carcinoma non-invasively at an early stage due to its delayed presentation. Similarly, this also makes it difficult to demonstrate an association between Ca Pancreas and other vital organs of the body, such as the heart. A number of studies have proven a correlation between the heart and pancreatic cancer. The tumor of the pancreas affects the heart at the physiological, as well as the molecular, level. An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies. A comprehensive review of this correlation will aid researchers in conducting studies to help establish a definite relation between the two organs and discover ways to use it for the early detection of Ca Pancreas.PMID:37623681 | DOI:10.3390/jimaging9080149

J Fungi (Basel). 2023 Aug 8;9(8):834. doi: 10.3390/jof9080834.ABSTRACTThe use of microorganisms in industry has enabled the (over)production of various compounds (e.g., primary and secondary metabolites, proteins and enzymes) that are relevant for the production of antibiotics, food, beverages, cosmetics, chemicals and biofuels, among others. Industrial strains are commonly obtained by conventional (non-GMO) strain improvement strategies and random screening and selection. However, recombinant DNA technology has made it possible to improve microbial strains by adding, deleting or modifying specific genes. Techniques such as genetic engineering and genome editing are contributing to the development of industrial production strains. Nevertheless, there is still significant room for further strain improvement. In this review, we will focus on classical and recent methods, tools and technologies used for the development of fungal production strains with the potential to be applied at an industrial scale. Additionally, the use of functional genomics, transcriptomics, proteomics and metabolomics together with the implementation of genetic manipulation techniques and expression tools will be discussed.PMID:37623605 | DOI:10.3390/jof9080834

J Fungi (Basel). 2023 Jul 26;9(8):785. doi: 10.3390/jof9080785.ABSTRACTMany studies aim at maximizing fungal secondary metabolite production but the influence of light during cultivation has often been neglected. Here, we combined an untargeted isotope-assisted liquid chromatography-high-resolution mass spectrometry-based metabolomics approach with standardized cultivation of Trichoderma atroviride under three defined light regimes (darkness (PD), reduced light (RL) exposure, and 12/12 h light/dark cycle (LD)) to systematically determine the effect of light on secondary metabolite production. Comparative analyses revealed a similar metabolite profile upon cultivation in PD and RL, whereas LD treatment had an inhibiting effect on both the number and abundance of metabolites. Additionally, the spatial distribution of the detected metabolites for PD and RL was analyzed. From the more than 500 detected metabolites, only 25 were exclusively produced upon fungal growth in darkness and 85 were significantly more abundant in darkness. The majority were detected under both cultivation conditions and annotation revealed a cluster of substances whose production followed the pattern observed for the well-known T. atroviride metabolite 6-pentyl-alpha-pyrone. We conclude that cultivation of T. atroviride under RL can be used to maximize secondary metabolite production.PMID:37623556 | DOI:10.3390/jof9080785

Curr Issues Mol Biol. 2023 Aug 14;45(8):6701-6703. doi: 10.3390/cimb45080423.ABSTRACTThe study of plant metabolome and the role of cellular pathway end products has gained increased attention [...].PMID:37623242 | DOI:10.3390/cimb45080423

Int J Environ Res Public Health. 2023 Aug 17;20(16):6591. doi: 10.3390/ijerph20166591.ABSTRACTTraumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction in the acute and chronic time frames after the injury. Chronic SCI has well-described secondary medical consequences while acute SCI has unique metabolic challenges as a result of physical trauma, in-patient recovery and other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe the circulating lipidomic and metabolomic signatures using blood serum from mice 7 d after a complete SCI. Additionally, we probed whether the aporphine alkaloid, boldine, was able to prevent SCI-induced changes observed using these 'omics platforms'. We found that SCI resulted in large-scale changes to the circulating lipidome but minimal changes in the metabolome, with boldine able to reverse or attenuate SCI-induced changes in the abundance of 50 lipids. Multiomic integration using xMWAS demonstrated unique network structures and community memberships across the groups.PMID:37623175 | DOI:10.3390/ijerph20166591

Biosensors (Basel). 2023 Aug 3;13(8):785. doi: 10.3390/bios13080785.ABSTRACTIt is of great importance to have sensitive and accurate detection of cis-diol-containing biologically related substances because of their important functions in the research fields of metabolomics, glycomics, and proteomics. Boronic acids can specifically and reversibly interact with 1,2- or 1,3-diols to form five or six cyclic esters. Based on this unique property, boronic acid-based materials have been used as synthetic receptors for the specific recognition and detection of cis-diol-containing species. This review critically summarizes the recent advances with boronic acid-based materials as recognition elements and signal labels for the detection of cis-diol-containing biological species, including ribonucleic acids, glycans, glycoproteins, bacteria, exosomes, and tumor cells. We also address the challenges and future perspectives for developing versatile boronic acid-based materials with various promising applications.PMID:37622871 | DOI:10.3390/bios13080785

Pediatr Allergy Immunol. 2023 Aug;34(8):e14003. doi: 10.1111/pai.14003.ABSTRACTBACKGROUND: Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA.METHODS: We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry-based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA.RESULTS: In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid.CONCLUSION: Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.PMID:37622258 | DOI:10.1111/pai.14003

Front Cell Infect Microbiol. 2023 Aug 9;13:1134321. doi: 10.3389/fcimb.2023.1134321. eCollection 2023.ABSTRACTBACKGROUND AND PURPOSE: Microbiome dysfunction is known to aggravate acute pancreatitis (AP); however, the relationship between this dysfunction and metabolite alterations is not fully understood. This study explored the crosstalk between the microbiome and metabolites in AP mice.METHODS: Experimental AP models were established by injecting C57/BL mice with seven doses of cerulein and one dose of lipopolysaccharide (LPS). Metagenomics and untargeted metabolomics were used to identify systemic disturbances in the microbiome and metabolites, respectively, during the progression of AP.RESULTS: The gut microbiome of AP mice primarily included Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, and "core microbiota" characterized by an increase in Proteobacteria and a decrease in Actinobacteria. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that significantly different microbes were involved in several signaling networks. Untargeted metabolomics identified 872 metabolites, of which lipids and lipid-like molecules were the most impacted. An integrated analysis of metagenomics and metabolomics indicated that acetate kinase (ackA) gene expression was associated with various gut microbiota, including Alistipes, Butyricimonas, and Lactobacillus, and was strongly correlated with the metabolite daphnoretin. The functional gene, O-acetyl-L-serine sulfhydrylase (cysK), was associated with Alistipes, Jeotgalicoccus, and Lactobacillus, and linked to bufalin and phlorobenzophenone metabolite production.CONCLUSION: This study identified the relationship between the gut microbiome and metabolite levels during AP, especially the Lactobacillus-, Alistipes-, and Butyricimonas-associated functional genes, ackA and cysK. Expression of these genes was significantly correlated to the production of the anti-inflammatory and antitumor metabolites daphnoretin and bufalin.PMID:37621874 | PMC:PMC10446838 | DOI:10.3389/fcimb.2023.1134321

Front Microbiol. 2023 Aug 9;14:1175858. doi: 10.3389/fmicb.2023.1175858. eCollection 2023.ABSTRACTMagnesium hydride (MGH), a highly promising hydrogen-producing substance/additive for hydrogen production through its hydrolysis reaction, has the potential to enhance broiler production. However, before incorporating MGH as a hydrogen-producing additive in broiler feed, it is crucial to fully understand its impact on microbiota and metabolites. In vitro fermentation models provide a fast, reproducible, and direct assessment tool for microbiota metabolism and composition. This study aims to investigate the effects of MGH and coated-magnesium hydride (CMG) on fermentation characteristics, as well as the microbiota and metabolome in the culture of in vitro fermentation using cecal inocula from broilers. After 48 h of incubation, it was observed that the presence of MGH had a significant impact on various factors. Specifically, the content of N-NH3 decreased, while the total hydrogen gas and total SCFAs increased. Furthermore, the presence of MGH promoted the abundance of SCFA-producing bacteria such as Ruminococcus, Blautia, Coprobacillus, and Dysgonomonas. On the other hand, the presence of CMG led to an increase in the concentration of lactic acid, acetic acid, and valeric acid. Additionally, CMG affected the diversity of microbiota in the culture, resulting in an enrichment of the relative abundance of Firmicutes, as well as genera of Lactobacillus, Coprococcus, and Eubacterium. Conversely, the relative abundance of the phylum Proteobacteria and pathogenic bacteria Shigella decreased. Metabolome analysis revealed that MGH and CMG treatment caused significant changes in 21 co-regulated metabolites, primarily associated with lipid, amino acid, benzenoids, and organooxygen compounds. Importantly, joint correlation analysis revealed that MGH or CMG treatments had a direct impact on the microbiota, which in turn indirectly influenced metabolites in the culture. In summary, the results of this study suggested that both MGH and coated-MGH have similar yet distinct positive effects on the microbiota and metabolites of the broiler cecal in an in vitro fermentation model.PMID:37621394 | PMC:PMC10445219 | DOI:10.3389/fmicb.2023.1175858

Andrology. 2023 Aug 24. doi: 10.1111/andr.13515. Online ahead of print.ABSTRACTDespite its efficacy for treating androgenetic alopecia, finasteride, an inhibitor of 5α-reductase (i.e., the enzyme converting testosterone, T, into dihydrotestosterone, DHT), is associated with several side effects including sexual dysfunction (e.g., erectile dysfunction). These side effects may persist after drug suspension, inducing the so-called post-finasteride syndrome (PFS). The effects of subchronic treatment with finasteride (i.e., 20 days) and its withdrawal (i.e., 1 month) in rat corpus cavernosum have been explored here. Data obtained show that the treatment was able to decrease the levels of the enzyme 5α-reductase type II in the rat corpus cavernosum with increased T and decreased DHT levels. This local change in T metabolism was linked to mechanisms associated with erectile dysfunction. Indeed, by targeted metabolomics, we reported a decrease in the nitric oxide synthase (NOS) activity, measured by the citrulline/arginine ratio and confirmed by the decrease in NO2 levels, and a decrease in ornithine transcarbamylase (OTC) activity, measured by citrulline/ornithine ratio. Interestingly, the T levels are negatively correlated with NOS activity, while those of DHT are positively correlated with OTC activity. Finasteride treatment also induced alterations in the levels of other molecules involved in the control of penile erection, such as norepinephrine and its metabolite, epinephrine. Indeed, plasma levels of norepinephrine and epinephrine were significantly increased and decreased, respectively, suggesting an impairment of these mediators. Interestingly, these modifications were restored by suspension of the drug. Altogether, the results reported here indicate that finasteride treatment, but not its withdrawal, affects T metabolism in the rat corpus cavernosum, and this alteration was linked to mechanisms associated with erectile dysfunction. Data here reported could also suggest that the PFS sexual side effects are more related to dysfunction in a sexual central control rather than peripheral compromised condition.PMID:37621185 | DOI:10.1111/andr.13515

J Sci Food Agric. 2023 Aug 24. doi: 10.1002/jsfa.12927. Online ahead of print.ABSTRACTBACKGROUND: Amino acids (AAs) are important protein building blocks that play a critical role in the function of the immune system. However, comprehensive comparative metabolomics and antigenicity analyses of cow milk (CM) and enzymatically-treated CM are relatively scarce. Herein, we analyzed the AAs in the CM and flavourzyme-treated milk groups (FT), and their antigenicity was also explored.RESULTS: Overall, 50 AAs were detected in CM and FT, with 23 significantly different AAs. The interaction network of these significantly different AAs was analyzed, and 34 significantly different metabolic pathways were found to be involved. In addition, we found that the antigenicity of FT was significantly reduced compared to that of CM.CONCLUSION: These results enhance our understanding of AAs and antigenicity regarding CM and FT, and provide new ideas and directions for the development of high-quality hypoallergenic dairy products. This article is protected by copyright. All rights reserved.PMID:37621148 | DOI:10.1002/jsfa.12927

Virulence. 2023 Dec;14(1):2249790. doi: 10.1080/21505594.2023.2249790.ABSTRACTTranslocon pores formed in the eukaryotic cell membrane by a type III secretion system facilitate the translocation of immune-modulatory effector proteins into the host cell interior. The YopB and YopD proteins produced and secreted by pathogenic Yersinia spp. harboring a virulence plasmid-encoded type III secretion system perform this pore-forming translocator function. We had previously characterized in vitro T3SS function and in vivo pathogenicity of a number of strains encoding sited-directed point mutations in yopD. This resulted in the classification of mutants into three different classes based upon the severity of the phenotypic defects. To investigate the molecular and functional basis for these defects, we explored the effectiveness of RAW 264.7 cell line to respond to infection by representative YopD mutants of all three classes. Signature cytokine profiles could separate the different YopD mutants into distinct categories. The activation and suppression of certain cytokines that function as central innate immune response modulators correlated well with the ability of mutant bacteria to alter anti-phagocytosis and programmed cell death pathways. These analyses demonstrated that sub-optimal translocon pores impact the extent and magnitude of host cell responsiveness, and this limits the capacity of pathogenic Yersinia spp. to fortify against attack by both early and late arms of the host innate immune response.PMID:37621095 | DOI:10.1080/21505594.2023.2249790

Environ Microbiol. 2023 Aug 24. doi: 10.1111/1462-2920.16485. Online ahead of print.ABSTRACTGlaciers host ecosystems comprised of biodiverse and active microbiota. Among glacial ecosystems, less is known about the ecology of ice caps since most studies focus on valley glaciers or ice sheet margins. Previously we detailed the microbiota of one such high Arctic ice cap, focusing on cryoconite as a microbe-mineral aggregate formed by cyanobacteria. Here, we employ metabolomics at the scale of an entire ice cap to reveal the major metabolic pathways prevailing in the cryoconite of Foxfonna, central Svalbard. We reveal how geophysical and biotic processes influence the metabolomes of its resident cryoconite microbiota. We observed differences in amino acid, fatty acid, and nucleotide synthesis across the cap reflecting the influence of ice topography and the cyanobacteria within cryoconite. Ice topography influences central carbohydrate metabolism and nitrogen assimilation, whereas bacterial community structure governs lipid, nucleotide, and carotenoid biosynthesis processes. The prominence of polyamine metabolism and nitrogen assimilation highlights the importance of recycling nitrogenous nutrients. To our knowledge, this study represents the first application of metabolomics across an entire ice mass, demonstrating its utility as a tool for revealing the fundamental metabolic processes essential for sustaining life in supraglacial ecosystems experiencing profound change due to Arctic climate change-driven mass loss.PMID:37621052 | DOI:10.1111/1462-2920.16485

Cardiovasc Diabetol. 2023 Aug 24;22(1):219. doi: 10.1186/s12933-023-01942-0.ABSTRACTBACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD.METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model.RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables.CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.PMID:37620823 | DOI:10.1186/s12933-023-01942-0

BMC Plant Biol. 2023 Aug 25;23(1):406. doi: 10.1186/s12870-023-04404-7.ABSTRACTBACKGROUND: Plants growing in the field are subjected to combinations of abiotic stresses. These conditions pose a devastating threat to crops, decreasing their yield and causing a negative economic impact on agricultural production. Metabolic responses play a key role in plant acclimation to stress and natural variation for these metabolic changes could be key for plant adaptation to fluctuating environmental conditions.RESULTS: Here we studied the metabolomic response of two Arabidopsis ecotypes (Columbia-0 [Col] and Landsberg erecta-0 [Ler]), widely used as genetic background for Arabidopsis mutant collections, subjected to the combination of high salinity and increased irradiance. Our findings demonstrate that this stress combination results in a specific metabolic response, different than that of the individual stresses. Although both ecotypes displayed reduced growth and quantum yield of photosystem II, as well as increased foliar damage and malondialdehyde accumulation, different mechanisms to tolerate the stress combination were observed. These included a relocation of amino acids and sugars to act as potential osmoprotectants, and the accumulation of different stress-protective compounds such as polyamines or secondary metabolites.CONCLUSIONS: Our findings reflect an initial identification of metabolic pathways that differentially change under stress combination that could be considered in studies of stress combination of Arabidopsis mutants that include Col or Ler as genetic backgrounds.PMID:37620776 | DOI:10.1186/s12870-023-04404-7

BMC Plant Biol. 2023 Aug 24;23(1):402. doi: 10.1186/s12870-023-04383-9.ABSTRACTBACKGROUND: Betalain is a natural pigment with important nutritional value and broad application prospects. Previously, we produced betanin biosynthesis transgenic carrots via expressing optimized genes CYP76AD1S, cDOPA5GTS and DODA1S. Betanin can accumulate throughout the whole transgenic carrots. But the effects of betanin accumulation on the metabolism of transgenic plants and whether it produces unexpected effects are still unclear.RESULTS: The accumulation of betanin in leaves can significantly improve its antioxidant capacity and induce a decrease of chlorophyll content. Transcriptome and metabolomics analysis showed that 14.0% of genes and 33.1% of metabolites were significantly different, and metabolic pathways related to photosynthesis and tyrosine metabolism were markedly altered. Combined analysis showed that phenylpropane biosynthesis pathway significantly enriched the differentially expressed genes and significantly altered metabolites.CONCLUSIONS: Results showed that the metabolic status was significantly altered between transgenic and non-transgenic carrots, especially the photosynthesis and tyrosine metabolism. The extra consumption of tyrosine and accumulation of betanin might be the leading causes.PMID:37620775 | DOI:10.1186/s12870-023-04383-9

Anal Bioanal Chem. 2023 Aug 25. doi: 10.1007/s00216-023-04910-5. Online ahead of print.ABSTRACTMetabolomics is a biochemical analysis tool for identifying metabolic phenotypes and used to reveal the pathogenic mechanisms of disease and to inform drug-targeted therapies. Carboxyl-containing metabolites (CCMs) account for an important proportion of the metabolome, but because of the diversity of physical and chemical properties of CCMs in biological samples, traditional liquid chromatography-mass spectrometry (LC-MS) targeted metabolome analysis methods cannot achieve simultaneous quantification of multiple types of CCMs. Therefore, we proposed for the first time a targeted metabolomics strategy using isoniazid derivatization combined with LC-MS/MS to simultaneously quantify 39 CCMs of 5 different types (short-chain fatty acids, amino acids, bile acids, phenylalanine and tryptophan metabolic pathway acids) with large polarity differences associated with Alzheimer's disease (AD) and significantly improve the detection coverage and sensitivity. The yields of isoniazid derivative CCMs were high and could guarantee the accuracy of CCM quantification. The LODs of CCMs increased significantly (1.25-2000-fold) after derivatization. The method showed good selectivity, intra-day and inter-day accuracies and precisions, and repeatability. There was no significant effect on the determination of CCMs in terms of matrix effect and recovery. CCMs showed good stability. And CCMs showed good stability under short-term storage and freeze-thaw cycles. At the same time, the regulatory effects of Schisandrae chinensis Fructus and Ginseng Radix et Rhizoma (SG) herb pair on CCM metabolic disorders in feces, urine, serum, and the brain of AD rats were elucidated from the perspective of targeted metabolomics. In combination with pharmacodynamic evaluation and gut microbiota analysis, the mechanism of SG herb pair on AD rats was comprehensively understood. In summary, this innovative isoniazid derivatization combined with a targeted metabolomics method has great potential for trace biological lineage analysis.PMID:37620605 | DOI:10.1007/s00216-023-04910-5

Nat Commun. 2023 Aug 24;14(1):5176. doi: 10.1038/s41467-023-40861-2.ABSTRACTIdentifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB's contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.PMID:37620341 | DOI:10.1038/s41467-023-40861-2

Nat Commun. 2023 Aug 24;14(1):5160. doi: 10.1038/s41467-023-40874-x.ABSTRACTThe relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.PMID:37620311 | DOI:10.1038/s41467-023-40874-x

Chem Biol Drug Des. 2023 Aug 24. doi: 10.1111/cbdd.14329. Online ahead of print.ABSTRACTRegulation of formate flux by a key folate enzyme, MTHFD2 (methylene tetrahydrofolate dehydrogenase 2) in cancer cells remains poorly understood. Green et al. (Nature Metabolism, 2023; 5: 642-659) showed an interesting phenomenon of "folate trapping" toxicity leads to cancer cell kill using a potent inhibitor (TH9619) against the dehydrogenase and cyclohydrolase (DC) activities of cytosolic methylenetetrahydrofolate dehydrogenase 1 (cMTHFD1) and nuclear methylenetetrahydrofolate dehydrogenase 2 (nMTHFD2), but not the mitochondrial MTHFD2 (mTHFD2). But, mMTHFD2 is required for formate flow to cytosol which leads to the trapping of 10-formyl tetrahydrofolate and causes toxicity by TH9619 treatment, to kill cancer cells expressing mMTHFD2. This article opens new avenues to be evaluated for therapeutic benefits of cancer patients where MTHFD2 shows overexpression viz-a-viz breast, prostate, colorectal, acute myeloid leukemia, and other cancer types.PMID:37620162 | DOI:10.1111/cbdd.14329