PubMed

Sci Total Environ. 2023 Jul 8:165348. doi: 10.1016/j.scitotenv.2023.165348. Online ahead of print.ABSTRACTCadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.PMID:37429473 | DOI:10.1016/j.scitotenv.2023.165348

Metab Eng. 2023 Jul 8:S1096-7176(23)00093-9. doi: 10.1016/j.ymben.2023.06.011. Online ahead of print.ABSTRACTVitamin E tocochromanols are generated in plants by prenylation of homogentisate using geranylgeranyl diphosphate (GGDP) for tocotrienol biosynthesis and phytyl diphosphate (PDP) for tocopherol biosynthesis. Homogentisate geranylgeranyl transferase (HGGT), which uses GGDP for prenylation, is a proven target for oilseed tocochromanol biofortification that effectively bypasses the chlorophyll-linked pathway that limits PDP for vitamin E biosynthesis. In this report, we explored the feasibility of maximizing tocochromanol production in the oilseed crop camelina (Camelina sativa) by combining seed-specific HGGT expression with increased biosynthesis and/or reduced homogentisate catabolism. Plastid-targeted Escherichia coli TyrA-encoded chorismate mutase/prephenate dehydrogenase and Arabidopsis hydroxyphenylpyruvate dioxygenase (HPPD) cDNA were co-expressed in seeds to bypass feedback-regulated steps and increase flux into homogentisate biosynthesis. Homogentisate catabolism was also suppressed by seed-specific RNAi of the gene for homogentisate oxygenase (HGO), which initiates homogentisate degradation. In the absence of HGGT expression, tocochromanols were increased by ∼2.5-fold with HPPD/TyrA co-expression, and ∼1.4-fold with HGO suppression compared to levels in non-transformed seeds. No further increase in tocochromanols was observed in HPPD/TyrA lines with the addition of HGO RNAi. HGGT expression alone increased tocochromanol concentrations in seeds by ∼four-fold to ≤1400 μg/g seed weight. When combined with HPPD/TyrA co-expression, we obtained an additional three-fold increase in tocochromanol concentrations indicating that homogentisate concentrations limit HGGT's capacity for maximal tocochromanol production. The addition of HGO RNAi further increased tocochromanol concentrations to 5000 μg/g seed weight, an unprecedented tocochromanol concentration in an engineered oilseed. Metabolomic data obtained from engineered seeds provide insights into phenotypic changes associated with "extreme" tocochromanol production.PMID:37429412 | DOI:10.1016/j.ymben.2023.06.011

Biomed Pharmacother. 2023 Jul 8;165:115150. doi: 10.1016/j.biopha.2023.115150. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by chronic airway inflammation and remodeling, which seriously endangers human health. Recent developments in genomics and metabolomics have revealed the roles of the gut microbiota and its metabolites in COPD. Dysbiosis of the gut microbiota directly increases gut permeability, thereby promoting the translocation of pathological bacteria. The gut microbiota and associated metabolites may influence the development and progression of COPD by modulating immunity and inflammation. Furthermore, the systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction. The cross-talk between the gut and lungs is known as the gut-lung axis; however, an overview of its mechanism is lacking. This review highlights the critical and complex interplay of gut microbiota and immune responses in the gut-lung axis, further explores possible links between the gut and lungs, and summarizes new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation, which are critical to COPD.PMID:37429232 | DOI:10.1016/j.biopha.2023.115150

J Pharm Biomed Anal. 2023 Jun 27;234:115550. doi: 10.1016/j.jpba.2023.115550. Online ahead of print.ABSTRACTFor centuries, Flos Trollii has been consumed as functional tea and a folk medicine in China's north and northwest zones. The quality of Flos Trollii highly depends on the producing zones. Unfortunately, few studies have been reported on the geographical discrimination of Flos Trollii. This work comprehensively investigated Flos Trollii compounds with an integration strategy combining gas chromatography-mass spectrometry (GC-MS) and ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) with chemometrics to explore the differences between Flos Trollii obtained from various origins of China. About 71 volatile and 22 involatile markers were identified with GC-MS and UHPLC-HRMS, respectively. Geographical discrimination models were synthetically investigated based on the identified markers. The results indicated that the UHPLC-HRMS coupled with the fisher discrimination model provided the best prediction capability (>97%). This study provides a new solution for Flos Trollii discrimination.PMID:37429118 | DOI:10.1016/j.jpba.2023.115550

Part Fibre Toxicol. 2023 Jul 10;20(1):26. doi: 10.1186/s12989-023-00537-7.ABSTRACTBACKGROUND: There is insufficient knowledge about the systemic health effects of exposure to fine (PM2.5) and ultrafine particles emitted from typical indoor sources, including cooking and candlelight burning. We examined whether short-term exposure to emissions from cooking and burning candles cause inflammatory changes in young individuals with mild asthma. Thirty-six non-smoking asthmatics participated in a randomized controlled double-blind crossover study attending three exposure sessions (mean PM2.5 µg/m3; polycyclic aromatic hydrocarbons ng/m3): (a) air mixed with emissions from cooking (96.1; 1.1), (b) air mixed with emissions from candles (89.8; 10), and (c) clean filtered air (5.8; 1.0). Emissions were generated in an adjacent chamber and let into a full-scale exposure chamber where participants were exposed for five hours. Several biomarkers were assessed in relation to airway and systemic inflammatory changes; the primary outcomes of interest were surfactant Protein-A (SP-A) and albumin in droplets in exhaled air - novel biomarkers for changes in the surfactant composition of small airways. Secondary outcomes included cytokines in nasal lavage, cytokines, C-reactive protein (CRP), epithelial progenitor cells (EPCs), genotoxicity, gene expression related to DNA-repair, oxidative stress, and inflammation, as well as metabolites in blood. Samples were collected before exposure start, right after exposure and the next morning.RESULTS: SP-A in droplets in exhaled air showed stable concentrations following candle exposure, while concentrations decreased following cooking and clean air exposure. Albumin in droplets in exhaled air increased following exposure to cooking and candles compared to clean air exposure, although not significant. Oxidatively damaged DNA and concentrations of some lipids and lipoproteins in the blood increased significantly following exposure to cooking. We found no or weak associations between cooking and candle exposure and systemic inflammation biomarkers including cytokines, CRP, and EPCs.CONCLUSIONS: Cooking and candle emissions induced effects on some of the examined health-related biomarkers, while no effect was observed in others; Oxidatively damaged DNA and concentrations of lipids and lipoproteins were increased in blood after exposure to cooking, while both cooking and candle emissions slightly affected the small airways including the primary outcomes SP-A and albumin. We found only weak associations between the exposures and systemic inflammatory biomarkers. Together, the results show the existence of mild inflammation following cooking and candle exposure.PMID:37430267 | DOI:10.1186/s12989-023-00537-7

Sci Rep. 2023 Jul 10;13(1):11129. doi: 10.1038/s41598-023-38318-z.ABSTRACTCurrently studies aiming for the comprehensive metabolomics profiling of measured total fat (%) as well as fat distribution in both sexes are lacking. In this work, bioimpedance analysis was applied to measure total fat (%) and fat distribution (trunk to leg ratio). Liquid chromatography-mass spectrometry-based untargeted metabolomics was employed to profile the metabolic signatures of total fat (%) and fat distribution in 3447 participants from three Swedish cohorts (EpiHealth, POEM and PIVUS) using a discovery-replication cross-sectional study design. Total fat (%) and fat distribution were associated with 387 and 120 metabolites in the replication cohort, respectively. Enriched metabolic pathways for both total fat (%) and fat distribution included protein synthesis, branched-chain amino acids biosynthesis and metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Four metabolites were mainly related to fat distribution: glutarylcarnitine (C5-DC), 6-bromotryptophan, 1-stearoyl-2-oleoyl-GPI (18:0/18:1) and pseudouridine. Five metabolites showed different associations with fat distribution in men and women: quinolinate, (12Z)-9,10-dihydroxyoctadec-12-enoate (9,10-DiHOME), two sphingomyelins and metabolonic lactone sulfate. To conclude, total fat (%) and fat distribution were associated with a large number of metabolites, but only a few were exclusively associated with fat distribution and of those metabolites some were associated with sex*fat distribution. Whether these metabolites mediate the undesirable effects of obesity on health outcomes remains to be further investigated.PMID:37429905 | DOI:10.1038/s41598-023-38318-z

EBioMedicine. 2023 Jul 8;94:104699. doi: 10.1016/j.ebiom.2023.104699. Online ahead of print.ABSTRACTBACKGROUND: Exposure to perfluoroalkyl substances may affect offspring immune development and thereby increase risk of childhood asthma, but the underlying mechanisms and asthma phenotype affected by such exposure is unknown.METHODS: In the Danish COPSAC2010 cohort of 738 unselected pregnant women and their children plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics analyses and calibrated using a targeted pipeline in mothers (gestation week 24 and 1 week postpartum) and children (age ½, 1½ and 6 years). We examined associations between pregnancy and childhood PFOS and PFOA exposure and childhood infections, asthma, allergic sensitization, atopic dermatitis, and lung function measures, and studied potential mechanisms by integrating data on systemic low-grade inflammation (hs-CRP), functional immune responses, and epigenetics.FINDINGS: Higher maternal PFOS and PFOA exposure during pregnancy showed association with a non-atopic asthma phenotype by age 6, a protection against sensitization, and no association with atopic asthma or lung function, or atopic dermatitis. The effect was primarily driven by prenatal exposure. There was no association with infection proneness, low-grade inflammation, altered immune responses or epigenetic changes.INTERPRETATIONS: Prenatal exposure to PFOS and PFOA, but not childhood exposure, specifically increased the risk of low prevalent non-atopic asthma, whereas there was no effect on atopic asthma, lung function, or atopic dermatitis.FUNDING: All funding received by COPSAC are listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Novo Nordic Foundation (Grant nos NNF20OC0061029, NNF170C0025014, NNF180C0031764); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B); and The Capital Region Research Foundation have provided core support to the COPSAC research center. COPSAC acknowledges the National Facility for Exposomics (SciLifeLab, Sweden) for supporting calibration of the untargeted metabolomics PFAS data. BC and AS has received funding for this project from the European Union's Horizon 2020 research and innovation programme (BC: grant agreement No. 946228 DEFEND; AS: grant agreement No. 864764 HEDIMED).PMID:37429082 | DOI:10.1016/j.ebiom.2023.104699

EBioMedicine. 2023 Jul 8;94:104703. doi: 10.1016/j.ebiom.2023.104703. Online ahead of print.ABSTRACTBACKGROUND: Mental symptoms have been shown to be associated with dementia. As the most common neuropsychiatric disorder, it is unclear whether and why anxiety increases the risk of cognitive progression in elderly.METHODS: The aim of this study was to investigate the longitudinal effects of anxiety on cognitive impairment in non-dementia elderly and to explore the underlying biological processes using multi-omics including microarray-based transcriptomics, mass spectrometry-based proteomics and metabolomics, cerebrospinal fluid (CSF) biochemical markers, and brain diffusion tensor imaging (DTI). The Alzheimer's Disease Neuroimaging Initiative (ADNI), Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Shanghai Mental Health Centre (SMHC) cohorts were included.FINDINGS: Anxiety was found to increase the risk of subsequent cognitive progression in the ADNI, and a similar result was observed in the CLHLS cohort. Enrichment analysis indicated activated axon/synapse pathways and suppressed mitochondrial pathways in anxiety, the former confirmed by deviations in frontolimbic tract morphology and altered levels of axon/synapse markers, and the latter supported by decreased levels of carnitine metabolites. Mediation analysis revealed that anxiety's effect on the longitudinal cognition was mediated by brain tau burden. Correlations of mitochondria-related expressed genes with axon/synapse proteins, carnitine metabolites, and cognitive changes were found.INTERPRETATION: This study provides cross-validated epidemiological and biological evidence that anxiety is a risk factor for cognitive progression in non-dementia elderly, and that axon/synapse damage in the context of energy metabolism imbalance may contribute to this phenomenon.FUNDING: The National Natural Science Foundation of China (82271607, 81971682, and 81830059) for data analysis and data collection.PMID:37429081 | DOI:10.1016/j.ebiom.2023.104703

J Proteome Res. 2023 Jul 10. doi: 10.1021/acs.jproteome.2c00602. Online ahead of print.ABSTRACTThe field of metabolomics has witnessed the development of hundreds of computational tools, but only a few have become cornerstones of this field. While MetaboLights and Metabolomics Workbench are two well-established data repositories for metabolomics data sets, Workflows4Metabolomics and MetaboAnalyst are two well-established web-based data analysis platforms for metabolomics. Yet, the raw data stored in the aforementioned repositories lack standardization in terms of the file system format used to store the associated acquisition files. Consequently, it is not straightforward to reuse available data sets as input data in the above-mentioned data analysis resources, especially for non-expert users. This paper presents CloMet, a novel open-source modular software platform that contributes to standardization, reusability, and reproducibility in the metabolomics field. CloMet, which is available through a Docker file, converts raw and NMR-based metabolomics data from MetaboLights and Metabolomics Workbench to a file format that can be used directly either in MetaboAnalyst or in Workflows4Metabolomics. We validated both CloMet and the output data using data sets from these repositories. Overall, CloMet fills the gap between well-established data repositories and web-based statistical platforms and contributes to the consolidation of a data-driven perspective of the metabolomics field by leveraging and connecting existing data and resources.PMID:37428859 | DOI:10.1021/acs.jproteome.2c00602

Anal Chem. 2023 Jul 10. doi: 10.1021/acs.analchem.3c01864. Online ahead of print.ABSTRACTAs the first step of metabolomic analysis in biomarker identification studies, various types of blood collection tubes are used in clinical practice. However, little attention is paid to potential contamination caused by the blank tube itself. Here, we evaluated small molecules in blank EDTA plasma tubes through LC-MS-based untargeted metabolomic analysis and identified small molecules with markedly varied levels among different production batches or specifications. Our data demonstrate possible contamination and data interference caused by blank EDTA plasma tubes when employing large clinical cohorts for biomarker identification. Therefore, we propose a workflow of filtering metabolites in blank tubes prior to statistical analysis to improve the fidelity of biomarker identification.PMID:37428854 | DOI:10.1021/acs.analchem.3c01864

FASEB J. 2023 Aug;37(8):e23086. doi: 10.1096/fj.202300395RRR.ABSTRACTCathepsin S (CTSS) is a widely expressed cysteinyl protease that has garnered attention because of its enzymatic and non-enzymatic functions under inflammatory and metabolic pathological conditions. Here, we examined whether CTSS participates in stress-related skeletal muscle mass loss and dysfunction, focusing on protein metabolic imbalance. Eight-week-old male wildtype (CTSS+/+ ) and CTSS-knockout (CTSS-/- ) mice were randomly assigned to non-stress and variable-stress groups for 2 weeks, and then processed for morphological and biochemical studies. Compared with non-stressed mice, stressed CTSS+/+ mice showed significant losses of muscle mass, muscle function, and muscle fiber area. In this setting, the stress-induced harmful changes in the levels of oxidative stress-related (gp91phox and p22phox ,), inflammation-related (SDF-1, CXCR4, IL-1β, TNF-α, MCP-1, ICAM-1, and VCAM-1), mitochondrial biogenesis-related (PPAR-γ and PGC-1α) genes and/or proteins and protein metabolism-related (p-PI3K, p-Akt, p-FoxO3α, MuRF-1, and MAFbx1) proteins; and these alterations were rectified by CTSS deletion. Metabolomic analysis revealed that stressed CTSS-/- mice exhibited a significant improvement in the levels of glutamine metabolism pathway products. Thus, these findings indicated that CTSS can control chronic stress-related skeletal muscle atrophy and dysfunction by modulating protein metabolic imbalance, and thus CTSS was suggested to be a promising new therapeutic target for chronic stress-related muscular diseases.PMID:37428652 | DOI:10.1096/fj.202300395RRR

Environ Sci Pollut Res Int. 2023 Jul 10. doi: 10.1007/s11356-023-28343-w. Online ahead of print.ABSTRACTIn recent years, environmental pollutants such as pesticide residues have become one of the severe public problems that endanger the ecological environment and affect human health. The development of biotechnology to rapidly and efficiently degrade pesticides is essential to reduce their environmental risks. Azoxystrobin (AZ) is representative of the most widely used agricultural fungicide in the world. A large number of studies have shown that AZ has toxic effects on non-target organisms such as fish, algae, earthworms, etc., which may pose a potential threat to the environmental ecosystem. Therefore, it is particularly important to develop new AZ phytoremediation methods. Based on the constructed Arabidopsis UGT72E2 knockout (KO) and overexpression (OE) lines, this study found that overexpression of UGT72E2 in Arabidopsis can enhance resistance to exogenous AZ stress and maintain a relatively stable physiological state while enhancing the metabolic degradation of AZ. Correspondingly, knockout mutants showed the opposite results. The results showed that the AZ glycosylation and malonyl glycosylation products produced by UGT72E2 overexpression lines increased by 10%~20% compared with normal lines, and increased by 7%~47% compared with gene knockout plants, and exhibited lower phytotoxicity. In summary, our findings highlight the critical role of UGT72E2 overexpression in constructing new varieties of phytoremediation and may provide new ideas for reducing the indirect or direct risks of pesticides or other environmental pollutants to non-target organisms and improving biological and environmental resilience.PMID:37428316 | DOI:10.1007/s11356-023-28343-w

ACS Infect Dis. 2023 Jul 10. doi: 10.1021/acsinfecdis.2c00585. Online ahead of print.ABSTRACTIntra-household contacts (HCs) of leprosy patients are at increased risk of infection by Mycobacterium leprae and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy. In this study, we investigated retrospective sera of leprosy HCs by liquid chromatography-mass spectrometry and enzyme-linked immunoassay to determine whether circulating levels of ω-3 and ω-6 PUFA metabolites were altered in HCs that developed leprosy (HCDL) in comparison to those that did not (HCNDL). Sera were collected from HCs at the time of index case diagnosis and before clinical signs/symptoms of leprosy. Our findings showed that HCDL sera exhibited a distinct metabolic profile in comparison to HCDNL. Specifically, arachidonic acid, leukotriene B4, 11-hydroxyeicosatetraenoic acid, prostaglandin D2, and lipoxin A4 were elevated in HCDL. In contrast, prostaglandin E2 levels were reduced in HCDL. The ω-3 PUFAs, docosahexaenoic acid, eicosapentaenoic acid, and the docosahexaenoic acid-derived resolvin D1 and maresin-1 were also elevated in HCDL individuals compared to HCNDL. Principal component analyses provided further evidence that lipid mediators could serve as an early biomarker for progression to active leprosy. A logistic model identified resolvin D1 and D2, and prostaglandin D2 as having the greatest potential for early detection of HCs that will manifest leprosy.PMID:37428112 | DOI:10.1021/acsinfecdis.2c00585

Microbiol Spectr. 2023 Jul 10:e0059023. doi: 10.1128/spectrum.00590-23. Online ahead of print.ABSTRACTChanges in diet and environment can lead to acute diarrhea in companion animals, but the composition and interactions of the gut microbiome during acute diarrhea remain unclear. In this multicenter case-control study, we investigated the relationship between intestinal flora and acute diarrhea in two breeds of cats. Acutely diarrheic American Shorthair (MD, n = 12) and British Shorthair (BD, n = 12) and healthy American Shorthair (MH, n = 12) and British Shorthair (BH, n = 12) cats were recruited. Gut microbial 16S rRNA sequencing, metagenomic sequencing, and untargeted metabolomic analysis were performed. We observed significant differences in beta-diversity (Adonis, P < 0.05) across breeds and disease state cohorts. Profound differences in gut microbial structure and function were found between the two cat breeds. In comparison to healthy British Shorthair cats, Prevotella, Providencia, and Sutterella were enriched while Blautia, Peptoclostridium, and Tyzzerella were reduced in American Shorthair cats. In the case-control cohort, cats with acute diarrhea exhibited an increased abundance of Bacteroidota, Prevotella, and Prevotella copri and a decreased abundance of Bacilli, Erysipelotrichales, and Erysipelatoclostridiaceae (both MD and BD cats, P < 0.05). Metabolomic analysis identified significant changes in the BD intestine, affecting 45 metabolic pathways. Moreover, using a random forest classifier, we successfully predicted the occurrence of acute diarrhea with an area under the curve of 0.95. Our findings indicate a distinct gut microbiome profile that is associated with the presence of acute diarrhea in cats. However, further investigations using larger cohorts of cats with diverse conditions are required to validate and extend these findings. IMPORTANCE Acute diarrhea is common in cats, and our understanding of the gut microbiome variations across breeds and disease states remains unclear. We investigated the gut microbiome of two cat breeds (British Shorthair and American Shorthair) with acute diarrhea. Our study revealed significant effects of breeds and disease states on the structure and function of the gut microbiota in cats. These findings emphasize the need to consider breed-related factors in animal nutrition and research models. Additionally, we observed an altered gut metabolome in cats with acute diarrhea, closely linked to changes in bacterial genera. We identified a panel of microbial biomarkers with high diagnostic accuracy for feline acute diarrhea. These findings provide novel insights into the diagnosis, classification, and treatment of feline gastrointestinal diseases.PMID:37428087 | DOI:10.1128/spectrum.00590-23

Phytother Res. 2023 Jul 10. doi: 10.1002/ptr.7926. Online ahead of print.ABSTRACTCryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation-induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut-lung axis angle, specifically focusing on the bile acid (BA)-gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs-targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation-induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation-induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF.PMID:37427974 | DOI:10.1002/ptr.7926

Biol Reprod. 2023 Jul 10:ioad074. doi: 10.1093/biolre/ioad074. Online ahead of print.ABSTRACTSperm storage by females after mating for species-dependent periods is used widely among animals with internal fertilization to allow asynchrony between mating and ovulation. Many mammals store sperm in the lower oviduct where specific glycans on oviduct epithelial cells retain sperm to form a reservoir. Binding to oviduct cells suppresses sperm intracellular Ca2+ and increases sperm longevity. We investigated the mechanisms by which a specific oviduct glycan, 3-O-sulfated Lewis X trisaccharide (suLeX), prolongs the lifespan of porcine sperm. Using targeted metabolomics, we found that binding to suLeX diminishes the abundance of 4-hydroxybenzoic acid, the precursor to ubiquinone (also known as Coenzyme Q), 30 min after addition. Ubiquinone functions as an electron acceptor in the electron transport chain (ETC). suLeX also suppressed the formation of fumarate. A component of the citric acid cycle, fumarate is synthesized by succinate-coenzyme Q reductase, which employs ubiquinone and is also known as Complex II in the electron transport chain. Consistent with the reduced activity of the electron transport chain, the production of harmful reactive oxygen species (ROS) was diminished. The enhanced sperm lifespan in the oviduct may be due to suppressed ROS production because high ROS concentrations have toxic effects on sperm.PMID:37427962 | DOI:10.1093/biolre/ioad074

Plant Physiol. 2023 Jul 10:kiad400. doi: 10.1093/plphys/kiad400. Online ahead of print.ABSTRACTWurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are two primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoids divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contribute to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae.PMID:37427874 | DOI:10.1093/plphys/kiad400

J Am Soc Mass Spectrom. 2023 Jul 10. doi: 10.1021/jasms.3c00171. Online ahead of print.ABSTRACTIsobaric tags typically leverage an a1 type fragmentation to produce constant mass reporter ions. While this motif allows for efficient reporter formation, isobaric tags lack structural diversity, which limits the number and type of isotopes that are synthetically available. Presented here are two examples of dual fragmentation isobaric tagging. The first example mimics the typical isobaric tag structure through trimethylamine neutral loss and cyclization. Subsequent fragmentation releases a constant mass reporter with high efficiency. This provides a route to create a variety of isobaric tags with regard to both the reporter and the balancer mass. The second example is a set of six-plex isobaric, thiol-reactive tags that produce constant mass reporters by a similar sequential fragmentation mechanism. A trimethylamine neutral loss allows for the incorporation of up to 13 total isotopes in the balancer region, while minimizing deuterium retention time shifts. A subsequent C-S bond cleavage produces a constant mass reporter in the low-mass region. The thiols investigated produced an average RSD of 14% and R2 of 0.98 when analyzed as a six-plex injection. Thiol metabolism was disrupted using the glutamyl-cysteine synthetase inhibitor buthionine sulfoximine (BSO). Endothelial cells were incubated with BSO and showed significant decreases in glutathione and cysteinyl-glycine compared to control. Overall, a new method to generate constant mass reporters using a dual fragmentation scheme is presented.PMID:37427806 | DOI:10.1021/jasms.3c00171

Plant Cell Environ. 2023 Jul 10. doi: 10.1111/pce.14664. Online ahead of print.ABSTRACTHigh-temperature stress limits plant growth and reproduction. Exposure to high temperature, however, also elicits a physiological response, which protects plants from the damage evoked by heat. This response involves a partial reconfiguration of the metabolome including the accumulation of the trisaccharide raffinose. In this study, we explored the intraspecific variation of warm temperature-induced raffinose accumulation as a metabolic marker for temperature responsiveness with the aim to identify genes that contribute to thermotolerance. By combining raffinose measurements in 250 Arabidopsis thaliana accessions following a mild heat treatment with genome-wide association studies, we identified five genomic regions that were associated with the observed trait variation. Subsequent functional analyses confirmed a causal relationship between TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1) and warm temperature-dependent raffinose synthesis. Moreover, complementation of the tps1-1 null mutant with functionally distinct TPS1 isoforms differentially affected carbohydrate metabolism under more severe heat stress. While higher TPS1 activity was associated with reduced endogenous sucrose levels and thermotolerance, disruption of trehalose 6-phosphate signalling resulted in higher accumulation of transitory starch and sucrose and was associated with enhanced heat resistance. Taken together, our findings suggest a role of trehalose 6-phosphate in thermotolerance, most likely through its regulatory function in carbon partitioning and sucrose homoeostasis.PMID:37427798 | DOI:10.1111/pce.14664

J Pak Med Assoc. 2023 Jun;73(6):1349-1352. doi: 10.47391/JPMA.23-47.ABSTRACTInstitute of Biomedical Sciences (IBMS) at Dow University of Health Sciences (DUHS), organised a two day's conference on Biomedical Sciences. IBMS being the part of one of the largest public sector health universities of Pakistan, is now transforming the research trends to be effectively translated at the community level. Currently with a strong PhD faculty line in basic and clinical sciences, DUHS has a significant contribution in research output of the country. The scientific data however represents a small population per scientific study and the generalization of results may not be inferred. It must be extended through translational research for effectiveness. The conference was planned with a theme to bridge the gap between basic and translational research. The two day's conference conducted in second week of March 2023 at Dow International Medical College Ojha Campus DUHS was able to attract more than 300 participants. The scientific sessions encompassed a vast variety of health issues and their proposed solutions including neurosciences, virtual biopsies, metabolomics, medical writings and incorporation of engineering and artificial intelligence to facilitate detection and prognosis of disease. The conference was able to conclude that the multidisciplinary research studies with collaboration of two or more institutes/organizations are the need of time. Young researchers need an effective platform to showcase their research and make collaborations. Moreover, the incorporation of artificial intelligence would enhance patient care within health systems.PMID:37427652 | DOI:10.47391/JPMA.23-47