PubMed

Front Vet Sci. 2024 Apr 17;11:1328513. doi: 10.3389/fvets.2024.1328513. eCollection 2024.ABSTRACTINTRODUCTION: Despite the potential health risks associated with feeding raw and non-traditional diets, the use of these diets in dogs is increasing, yet the health outcomes associated with these diets is not well understood. This study investigates the effect of feeding dogs a kibble or raw meat-based diets on fecal microbiota composition, serum metabolomics and inflammatory markers.METHODS: Clinically healthy dogs with a history of consuming either kibble (KD, n = 27) or raw meat-based diets (RMBD, n = 28) for more than 1 year were enrolled. Dogs were fed a standardized diet of either a single brand of KD or RMBD for 28 days. Serum and fecal samples were collected for analysis of microbiota, metabolomics, and inflammatory markers. Multiple regression analysis was performed for each of the metabolites and inflammatory markers, with feed group, age and BCS included as independent variables.RESULTS: The fecal microbiota composition differed between the KD and RMBD groups. Beta-diversity and some indices of alpha-diversity (i.e., Shannon and Simpson) were different between the two diet groups. Sixty- three serum metabolites differed between KD and RMBD-fed dogs with the majority reflecting the differences in macronutrient composition of the two diets.Fecal IAP, IgG and IgA were significantly higher in RMBD dogs compared to KD dogs, while systemic markers of inflammation, including serum c-reactive protein (CRP), galectin, secretory receptor of advanced glycation end-products (sRAGE), haptoglobin, and serum IgG were similar in dogs fed either diet.DISCUSSION: Diet composition significantly affected fecal microbiota composition and metabolome. Although it had a potentially beneficial effect on local inflammatory markers, feeding RMBD had no impact on systemic inflammation. The influence of these changes on long term health outcomes provides an area for future study.PMID:38694479 | PMC:PMC11061498 | DOI:10.3389/fvets.2024.1328513

Front Physiol. 2024 Apr 17;15:1371096. doi: 10.3389/fphys.2024.1371096. eCollection 2024.ABSTRACTINTRODUCTION: The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.METHOD: Age-matched Gramd1c +/+ and Gramd1c -/- mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterol-derived metabolites were assessed in the feces, liver, and plasma.RESULTS: Compared to wild type controls (Gramd1c +/+) mice, mice lackingGramd1c (Gramd1c -/-) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c +/+ controls, Gramd1c -/- mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c -/- mice. Bulk RNA sequencing in the liver showed that Gramd1c -/- mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions.DISCUSSION: Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.PMID:38694206 | PMC:PMC11061533 | DOI:10.3389/fphys.2024.1371096

Research (Wash D C). 2024 Apr 29;7:0363. doi: 10.34133/research.0363. eCollection 2024.ABSTRACTCombined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.PMID:38694198 | PMC:PMC11062505 | DOI:10.34133/research.0363

Heliyon. 2024 Apr 26;10(9):e30420. doi: 10.1016/j.heliyon.2024.e30420. eCollection 2024 May 15.ABSTRACTOBJECTIVE: This study employs bibliometric and visual analysis to elucidate global research trends in Autism Spectrum Disorder (ASD) biomarkers, identify critical research focal points, and discuss the potential integration of diverse biomarker modalities for precise ASD assessment.METHODS: A comprehensive bibliometric analysis was conducted using data from the Web of Science Core Collection database until December 31, 2022. Visualization tools, including R, VOSviewer, CiteSpace, and gCLUTO, were utilized to examine collaborative networks, co-citation patterns, and keyword associations among countries, institutions, authors, journals, documents, and keywords.RESULTS: ASD biomarker research emerged in 2004, accumulating a corpus of 4348 documents by December 31, 2022. The United States, with 1574 publications and an H-index of 213, emerged as the most prolific and influential country. The University of California, Davis, contributed significantly with 346 publications and an H-index of 69, making it the leading institution. Concerning journals, the Journal of Autism and Developmental Disorders, Autism Research, and PLOS ONE were the top three publishers of ASD biomarker-related articles among a total of 1140 academic journals. Co-citation and keyword analyses revealed research hotspots in genetics, imaging, oxidative stress, neuroinflammation, gut microbiota, and eye tracking. Emerging topics included "DNA methylation," "eye tracking," "metabolomics," and "resting-state fMRI."CONCLUSION: The field of ASD biomarker research is dynamically evolving. Future endeavors should prioritize individual stratification, methodological standardization, the harmonious integration of biomarker modalities, and longitudinal studies to advance the precision of ASD diagnosis and treatment.PMID:38694128 | PMC:PMC11061761 | DOI:10.1016/j.heliyon.2024.e30420

J Inherit Metab Dis. 2024 May 1. doi: 10.1002/jimd.12734. Online ahead of print.ABSTRACTHumans derive fatty acids (FA) from exogenous dietary sources and/or endogenous synthesis from acetyl-CoA, although some FA are solely derived from exogenous sources ("essential FA"). Once inside cells, FA may undergo a wide variety of different modifications, which include their activation to their corresponding CoA ester, the introduction of double bonds, the 2- and ω-hydroxylation and chain elongation, thereby generating a cellular FA pool which can be used for the synthesis of more complex lipids. The biological properties of complex lipids are very much determined by their molecular composition in terms of the FA incorporated into these lipid species. This immediately explains the existence of a range of genetic diseases in man, often with severe clinical consequences caused by variants in one of the many genes coding for enzymes responsible for these FA modifications. It is the purpose of this review to describe the current state of knowledge about FA homeostasis and the genetic diseases involved. This includes the disorders of FA activation, desaturation, 2- and ω-hydroxylation, and chain elongation, but also the disorders of FA breakdown, including disorders of peroxisomal and mitochondrial α- and β-oxidation.PMID:38693715 | DOI:10.1002/jimd.12734

J Am Chem Soc. 2024 May 1. doi: 10.1021/jacs.4c04672. Online ahead of print.ABSTRACTPeptide-receptor interactions play critical roles in a wide variety of physiological processes. Methods to link bioactive peptides covalently to unmodified receptors on the surfaces of living cells are valuable for studying receptor signaling, dynamics, and trafficking and for identifying novel peptide-receptor interactions. Here, we utilize peptide analogues bearing deactivated aryl diazonium groups for the affinity-driven labeling of unmodified receptors. We demonstrate that aryl diazonium-bearing peptide analogues can covalently label receptors on the surface of living cells using both the neurotensin and the glucagon-like peptide 1 receptor systems. Receptor labeling occurs in the complex environment of the cell surface in a sequence-specific manner. We further demonstrate the utility of this covalent labeling approach for the visualization of peptide receptors by confocal fluorescence microscopy and for the enrichment and identification of labeled receptors by mass spectrometry-based proteomics. Aryl diazonium-based affinity-driven receptor labeling is attractive due to the high abundance of tyrosine and histidine residues susceptible to azo coupling in the peptide binding sites of receptors, the ease of incorporation of aryl diazonium groups into peptides, and the relatively small size of the aryl diazonium group. This approach should prove to be a powerful and relatively general method to study peptide-receptor interactions in cellular contexts.PMID:38693710 | DOI:10.1021/jacs.4c04672

Anal Chem. 2024 May 1. doi: 10.1021/acs.analchem.4c01253. Online ahead of print.ABSTRACTIon mobility-mass spectrometry (IM-MS) offers benefits for lipidomics by obtaining IM-derived collision cross sections (CCS), a conditional property of an ion that can enhance lipid identification. While drift tube (DT) IM-MS retains a direct link to the primary experimental method to derive CCS values, other IM technologies rely solely on external CCS calibration, posing challenges due to dissimilar chemical properties between lipids and calibrants. To address this, we introduce MobiLipid, a novel tool facilitating the CCS quality control of IM-MS lipidomics workflows by internal standardization. MobiLipid utilizes a newly established DTCCSN2 library for uniformly (U)13C-labeled lipids, derived from a U13C-labeled yeast extract, containing 377 DTCCSN2 values. This automated open-source R Markdown tool enables internal monitoring and straightforward compensation for CCSN2 biases. It supports lipid class- and adduct-specific CCS corrections, requiring only three U13C-labeled lipids per lipid class-adduct combination across 10 lipid classes without requiring additional external measurements. The applicability of MobiLipid is demonstrated for trapped IM (TIM)-MS measurements of an unlabeled yeast extract spiked with U13C-labeled lipids. Monitoring the CCSN2 biases of TIMCCSN2 values compared to DTCCSN2 library entries utilizing MobiLipid resulted in mean absolute biases of 0.78% and 0.33% in positive and negative ionization mode, respectively. By applying the CCS correction integrated into the tool for the exemplary data set, the mean absolute CCSN2 biases of 10 lipid classes could be reduced to approximately 0%.PMID:38693701 | DOI:10.1021/acs.analchem.4c01253

Eur J Nucl Med Mol Imaging. 2024 May 2. doi: 10.1007/s00259-024-06698-7. Online ahead of print.ABSTRACTBACKGROUND: Circulating-tumor DNA (ctDNA) and prostate-specific membrane antigen (PSMA) ligand positron-emission tomography (PET) enable minimal-invasive prostate cancer (PCa) detection and survival prognostication. The present study aims to compare their tumor discovery abilities and prognostic values.METHODS: One hundred thirty men with confirmed PCa (70.5 ± 8.0 years) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) imaging and plasma sample collection (March 2019-August 2021) were included. Plasma-extracted cell-free DNA was subjected to whole-genome-based ctDNA analysis. PSMA-positive tumor lesions were delineated and their quantitative parameters extracted. ctDNA and PSMA PET/CT discovery rates were compared, and the prognostic value for overall survival (OS) was evaluated.RESULTS: PSMA PET discovery rates according to castration status and PSA ranges did differ significantly (P = 0.013, P < 0.001), while ctDNA discovery rates did not (P = 0.311, P = 0.123). ctDNA discovery rates differed between localized and metastatic disease (P = 0.013). Correlations between ctDNA concentrations and PSMA-positive tumor volume (PSMA-TV) were significant in all (r = 0.42, P < 0.001) and castration-resistant (r = 0.65, P < 0.001), however not in hormone-sensitive patients (r = 0.15, P = 0.249). PSMA-TV and ctDNA levels were associated with survival outcomes in the Logrank (P < 0.0001, P < 0.0001) and multivariate Cox regression analysis (P = 0.0023, P < 0.0001).CONCLUSION: These findings suggest that PSMA PET imaging outperforms ctDNA analysis in detecting prostate cancer across the whole spectrum of disease, while both modalities are independently highly prognostic for survival outcomes.PMID:38693454 | DOI:10.1007/s00259-024-06698-7

Nature. 2024 May;629(8010):174-183. doi: 10.1038/s41586-023-06877-w. Epub 2024 May 1.ABSTRACTRegular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).PMID:38693412 | DOI:10.1038/s41586-023-06877-w

Sci Rep. 2024 May 1;14(1):10023. doi: 10.1038/s41598-024-60411-0.ABSTRACTExtreme high temperature has deleterious impact on the yield and quality of tea production, which has aroused the attention of growers and breeders. However, the mechanisms by which tea plant varieties respond to extreme environmental heat is not clear. In this study, we analyzed physiological indices, metabolites and transcriptome differences in three different heat-tolerant tea plant F1 hybrid progenies. Results showed that the antioxidant enzyme activity, proline, and malondialdehyde were significantly decreased in heat-sensitive 'FWS' variety, and the accumulation of reactive oxygen molecules such as H2O2 and O2- was remarkably increased during heat stress. Metabolomic analysis was used to investigate the metabolite accumulation pattern of different varieties in response to heat stress. The result showed that a total of 810 metabolites were identified and more than 300 metabolites were differentially accumulated. Transcriptional profiling of three tea varieties found that such genes encoding proteins with chaperon domains were preferentially expressed in heat-tolerant varieties under heat stress, including universal stress protein (USP32, USP-like), chaperonin-like protein 2 (CLP2), small heat shock protein (HSP18.1), and late embryogenesis abundant protein (LEA5). Combining metabolomic with transcriptomic analyses discovered that the flavonoids biosynthesis pathway was affected by heat stress and most flavonols were up-regulated in heat-tolerant varieties, which owe to the preferential expression of key FLS genes controlling flavonol biosynthesis. Take together, molecular chaperons, or chaperon-like proteins, flavonols accumulation collaboratively contributed to the heat stress adaptation in tea plant. The present study elucidated the differences in metabolite accumulation and gene expression patterns among three different heat-tolerant tea varieties under extreme ambient high temperatures, which helps to reveal the regulatory mechanisms of tea plant adaptation to heat stress, and provides a reference for the breeding of heat-tolerant tea plant varieties.PMID:38693343 | DOI:10.1038/s41598-024-60411-0

Nat Commun. 2024 May 1;15(1):3675. doi: 10.1038/s41467-024-48009-6.ABSTRACTThe wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed to perform specific tasks in LC-MS based metabolomics data analysis. Here we introduce MetaboAnalystR 4.0 as a streamlined pipeline covering raw spectra processing, compound identification, statistical analysis, and functional interpretation. The key features of MetaboAnalystR 4.0 includes an auto-optimized feature detection and quantification algorithm for LC-MS1 spectra processing, efficient MS2 spectra deconvolution and compound identification for data-dependent or data-independent acquisition, and more accurate functional interpretation through integrated spectral annotation. Comprehensive validation studies using LC-MS1 and MS2 spectra obtained from standards mixtures, dilution series and clinical metabolomics samples have shown its excellent performance across a wide range of common tasks such as peak picking, spectral deconvolution, and compound identification with good computing efficiency. Together with its existing statistical analysis utilities, MetaboAnalystR 4.0 represents a significant step toward a unified, end-to-end workflow for LC-MS based global metabolomics in the open-source R environment.PMID:38693118 | DOI:10.1038/s41467-024-48009-6

Transplant Proc. 2024 Apr 30:S0041-1345(24)00182-9. doi: 10.1016/j.transproceed.2024.03.012. Online ahead of print.ABSTRACTNutritional assessment is used to implement early nutritional interventions and reduce complications associated with malnutrition, which plays a crucial role in improving postoperative outcomes for patients undergoing pancreas and/or kidney transplantation.OBJECTIVE: The aim of this study was to analyze the nutritional status (NS) in patients eligible for kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx).METHODS: We analyzed the database of hospitalized patients from 2020 to 2023 to identify preoperative parameters of NS in patients eligible for KTx and SPKTx. A total of 59 patients participated in the study, all of whom were candidates for KTx-23 or SPKTx-36. The study population consisted of 35 women (W) and 24 men (M), with an overall mean age of 44.8 ± 10.2 years (43.5 ± 10.2 years for W and 46.2 ± 10.9 years for M). Both groups included patients on hemodialysis (n = 34) and peritoneal dialysis (n = 12), and patients in the predialysis period (pre-emptive, n = 13). The examined parameters included Onodera's prognostic nutritional index (PNIO), the nutritional risk index (NRI), proper body mass calculated using the Lorenz formula, and the neutrophil-to-lymphocyte ratio (NLR). All patients were assessed according to the NRS 2002 scale.RESULTS: Analysis of the obtained results revealed that the NLR was only one differentiating parameter between Ktx and SPKtx group. Multivariate analysis adjusted for patients' age and gender, comparing quantitative NS indicators was performed. Albumin serum concentration was not dependent on patients' group (KTx/SPKTx) neither age nor gender P = .382. BMI was dependent on patients' age and gender, but not a group (KTx/SPKTx) P = .008. PNIO, NRI, and NRL were not dependent on patients' group (KTx/SPKTx) neither age nor gender.CONCLUSIONS: Additional effort should be devoted to the development of a proper nutrition plan for SPKTx a especially in peritoneal dialysis patients. Toward patients on the waiting list, the regular assessment of nutritional status should be performed which is not a rule in dialysis centers. SPKTx candidates in the perioperative period should receive proper nutrition taking into account their caloric and protein needs.PMID:38692964 | DOI:10.1016/j.transproceed.2024.03.012

J Oleo Sci. 2024;73(5):695-708. doi: 10.5650/jos.ess23167.ABSTRACTThis study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.PMID:38692892 | DOI:10.5650/jos.ess23167

Int J Biol Macromol. 2024 Apr 29:131995. doi: 10.1016/j.ijbiomac.2024.131995. Online ahead of print.ABSTRACTIn the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)-β-D-Manp-(1 and 4)-β-D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the Bcl2/Bax/Caspase3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and Bcl2/Bax/Caspase3, resulting in protective effects against cognitive disorder.PMID:38692529 | DOI:10.1016/j.ijbiomac.2024.131995

Sci Total Environ. 2024 Apr 29:172796. doi: 10.1016/j.scitotenv.2024.172796. Online ahead of print.ABSTRACTLead (Pb) affects gene transcription, metabolite biosynthesis and growth in plants. The tung tree (Vernicia fordii) is highly adaptive to adversity, whereas the mechanisms underlying its response to Pb remain uncertain. In this work, transcriptomic and metabolomic analyses were employed to study tung trees under Pb stress. The results showed that the biomass of tung seedlings decreased with increasing Pb doses, and excessive Pb doses resulted in leaf wilting, root rot, and disruption of Pb homeostasis. Under non-excessive Pb stress, a significant change in the expression patterns of flavonoid biosynthesis genes was observed in the roots of tung seedlings, leading to changes in the accumulation of flavonoids in the roots, especially the upregulation of catechins, which can chelate Pb and reduce its toxicity in plants. In addition, Pb-stressed roots showed a large accumulation of VfWRKY55, VfWRKY75, and VfLRR1 transcripts, which were shown to be involved in the flavonoid biosynthesis pathway by gene module analysis. Overexpression of VfWRKY55, VfWRKY75, and VfLRR1 significantly increased catechin concentrations in tung roots, respectively. These data indicate that Pb stress-induced changes in the expression patterns of those genes regulate the accumulation of catechins. Our findings will help to clarify the molecular mechanism of Pb response in plants.PMID:38692325 | DOI:10.1016/j.scitotenv.2024.172796

Food Chem. 2024 Apr 17;451:139384. doi: 10.1016/j.foodchem.2024.139384. Online ahead of print.ABSTRACTThe economic impact of fruit cracking in pomegranate products is substantial. In this study, we present the inaugural comprehensive analysis of transcriptome and metabolome in the outermost pericarp of pomegranate fruit in bagging conditions. Our investigation revealed a notable upregulation of differentially expressed genes (DEGs) associated with the calcium signaling pathway (76.92%) and xyloglucan endotransglucosylase/hydrolase (XTH) genes (87.50%) in the fruit peel of non-cracking fruit under bagging. Metabolomic analysis revealed that multiple phenolics, flavonoids, and tannins were identified in pomegranate. Among these, calmodulin-like 23 (PgCML23) exhibited a significant correlation with triterpenoids and demonstrated a marked upregulation under bagging treatment. The transgenic tomatoes overexpressing PgCML23 exhibited significantly higher cellulose content and xyloglucan endotransglucosylase (XET) enzyme activity in the pericarp at the red ripening stage compared to the wild type. Conversely, water-soluble pectin content, polygalacturonase (PG), and β-galactosidase (β-GAL) enzyme activities were significantly lower in the transgenic tomatoes. Importantly, the heterologous expression of PgCML23 led to a substantial reduction in the fruit cracking rate in tomatoes. Our findings highlight the reduction of fruit cracking in bagging conditions through the manipulation of PgCML23 expression.PMID:38692235 | DOI:10.1016/j.foodchem.2024.139384

Biomed Pharmacother. 2024 Apr 30;175:116662. doi: 10.1016/j.biopha.2024.116662. Online ahead of print.ABSTRACT17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.PMID:38692064 | DOI:10.1016/j.biopha.2024.116662

J Hazard Mater. 2024 Apr 26;472:134425. doi: 10.1016/j.jhazmat.2024.134425. Online ahead of print.ABSTRACTSoil health is a crucial aspect of sustainable agriculture and food production, necessitating attention to the ecological risks associated with substantial amounts of mulch film residues. Biodegradable mulch films (BDMs) carry the same risk of mulch film residues formation as low-density polyethylene (LDPE) mulch films during actual use. More information is needed to elucidate the specific impacts of mulch film residues on the soil environment. Integrated 16S rRNA gene sequencing and non-targeted metabolomics, this study revealed the response patterns of bacterial communities, metabolites, and metabolic functions in the soil from three different agricultural regions to the presence of mulch film residues. LDPE mulch film residues negatively impacted the bacterial communities in the soils of Heilongjiang (HLJ) and Yunnan (YN) and had a lesser impact on the metabolic spectrum in the soils of HLJ, YN, and Xinjiang (XJ). BDM residues had a greater negative impact on all three soils in terms of both the bacterial communities and metabolites. The impact of BDM treatment on the soils of HLJ, YN, and XJ increased sequentially in that order. It is recommended that, when promoting the use of biodegradable mulch films, a fuller assessment should be made, accounting for local soil properties.PMID:38691998 | DOI:10.1016/j.jhazmat.2024.134425

Int Immunopharmacol. 2024 Apr 30;133:112132. doi: 10.1016/j.intimp.2024.112132. Online ahead of print.ABSTRACTOBJECTIVE: This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites.METHODS: We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases.RESULTS: Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08-1.27), psoriasis (OR 1.10; 95 % CI 1.04-1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23-1.63), pernicious anemia (OR 1.23; 95 % CI 1.12-1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11-1.26), alopecia areata (OR 1.22; 95 % CI 1.10-1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12-1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated.CONCLUSIONS: We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities.PMID:38691918 | DOI:10.1016/j.intimp.2024.112132

JCO Precis Oncol. 2024 Apr;8:e2300690. doi: 10.1200/PO.23.00690.ABSTRACTPURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN.METHODS: Lipidomic analysis was performed on plasma samples from 137 patients receiving taxane-based treatment. CIPN was graded using Total Neuropathy Score-clinical version (TNSc) and patient-reported outcome measure European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (EORTC-QLQ-CIPN20).RESULTS: A significant proportion of elevated baseline lipids were associated with high-grade CIPN defined by TNSc and EORTC-QLQ-CIPN20 including triacylglycerols (TGs). Multivariable Cox regression on lipid species, adjusting for BMI, age, and diabetes, showed several elevated baseline TG associated with shorter time to DR/CD. Latent class analysis identified two baseline lipid profiles with differences in risk of CIPN (hazard ratio, 2.80 [95% CI, 1.50 to 5.23]; P = .0013). The higher risk lipid profile had several elevated TG species and was independently associated with DR/CD when modeled with other clinical factors (diabetes, age, BMI, or prior numbness/tingling).CONCLUSION: Elevated baseline plasma TG is associated with an increased risk of CIPN development and warrants further validation in other cohorts. Ultimately, this may enable therapeutic intervention.PMID:38691814 | DOI:10.1200/PO.23.00690