PubMed

Environ Int. 2023 Dec 29;183:108412. doi: 10.1016/j.envint.2023.108412. Online ahead of print.ABSTRACTDue to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.PMID:38183898 | DOI:10.1016/j.envint.2023.108412

Mol Neurobiol. 2024 Jan 6. doi: 10.1007/s12035-023-03884-w. Online ahead of print.ABSTRACTAIMS: Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS.METHODS: We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS.RESULTS: We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism.CONCLUSION: 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.PMID:38183570 | DOI:10.1007/s12035-023-03884-w

Anim Microbiome. 2024 Jan 6;6(1):1. doi: 10.1186/s42523-023-00287-z.ABSTRACTBACKGROUND: Different types of exogenous protease supplements have a positive impact on animal performance, but their effects on the nutritional value of meat and the gut microbial community of broilers have not been extensively studied. The objective of this investigation was to determine the impact of supplementation with a novel alkaline protease derived from Bacillus licheniformis (at doses of 0, 100, 200, 300, and 400 g/t) on the fatty acid and amino acid profiles, inosine monophosphate (IMP) levels, total volatile basic nitrogen (TVB-N) content found within the breast muscle, as well as the impact on the cecal microbiota and metabolites.RESULTS: Supplementation with 200-400 g/t of the novel protease resulted in a significant elevation in the concentration of essential amino acids (P < 0.001), flavor amino acids (P < 0.001), and total protein (P = 0.013) within the breast muscle. Results derived from the 16S rRNA sequencing and untargeted metabolomics analysis of the cecal content revealed that the novel protease reshaped the cecal microbial and metabolite profiles. In particular, it led to increased relative abundances of Bacteroides, Lactobacillus, Alistipes, and Eubacterium, while simultaneously causing a reduction in the metabolites of D-lactic acid and malonic acid. Moreover, correlation analyses unveiled significant relationships between distinct microbes and metabolites with the contents of IMP, fatty acids, and amino acids in the broiler's breast muscle.CONCLUSION: In summary, the novel protease regulated the intestinal microbial community and metabolism, thereby inducing changes in the compositions of fatty acids and amino acids profiles, as well as IMP levels in broiler meat. These alterations significantly contributed to the enhancement of the nutritional value and flavor of the meat.PMID:38184648 | DOI:10.1186/s42523-023-00287-z

Cardiovasc Diabetol. 2024 Jan 6;23(1):13. doi: 10.1186/s12933-023-02094-x.ABSTRACTBACKGROUND: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D.METHODS: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E-I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students' t-test or Wilcoxon signed rank test as appropriate.RESULTS: Glucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: -51 ± 22 ml/s (p < 0.05); ΔE: -33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: -3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment.CONCLUSIONS: Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes.TRIAL REGISTRATION: EudraCT 2017-002101-35, August 2017.PMID:38184612 | DOI:10.1186/s12933-023-02094-x

Life Sci. 2024 Jan 4:122385. doi: 10.1016/j.lfs.2023.122385. Online ahead of print.ABSTRACTAIMS: This study aims to investigate the effects of berberine (BBR) on the intestinal microbiome (IM) and serum metabolome in ulcerative colitis (UC). Furthermore, the underlying molecular mechanisms of BBR in treating UC also will be explored systematically.MATERIALS AND METHODS: A multi-omics approach that integrates the 16s rDNA, serum metabolome, transcriptomics and bioinformatics was profiled to investigate the potential effects of BBR on the IM, serum metabolites and metabolic pathways, and gene expression. In addition, BBR-induced fecal microbiota transplantation (BBR_FMT) was conducted in pseudo germ-free mice combined with the UC model to explore the effects of the IM on metabolic pathways and gene expression. The results of the transcriptomics and metabolic pathway-related genes were further examined by real-time PCR and western blot.KEY FINDINGS: BBR ameliorated the community of IM and significantly promoted the abundance of f__Muribaculaceae, Bacteroides, Dubosiella, Allobaculum and Akkermansia. The metabolic profiles in UC mice were significantly modulated by BBR treatment. Furthermore, the inflammation-related metabolites and metabolic pathways in serum were negatively correlated with the abundance of Bacteroides and Akkermansia, which were induced by BBR treatment. BBR_FMT significantly inhibited the arachidonic acid (AA) metabolism pathway and its multiple markers with the mediation of the IM.SIGNIFICANCE: BBR ameliorated serum metabolic homeostasis by regulating the IM. The inhibition of the AA metabolism pathway and its multiple markers was one of the mechanisms of BBR in the treatment of UC.PMID:38184271 | DOI:10.1016/j.lfs.2023.122385

Sci Total Environ. 2024 Jan 4:169839. doi: 10.1016/j.scitotenv.2023.169839. Online ahead of print.ABSTRACTThere is a lack of studies on the ability of plants to metabolize chlorinated organic pollutants (COPs) and the dynamic expression changes of metabolic molecules during degradation. In this study, hybrid rice Chunyou 927 (CY) and Zhongzheyou 8 (ZZY), traditional rice subsp. Indica Baohan 1 (BH) and Xiangzaoxian 45 (XZX), and subsp. Japonica Yangjing 687 (YJ) and Longjing 31 (LJ) were stressed by a typical COPs of lindane and then transferred to a lindane-free culture to incubate for 9 days. The cumulative concentrations in the roots of BH, XZX, CY, ZZY, YJ and LJ were 71.46, 65.42, 82.06, 80.11, 47.59 and 56.10 mg·kg-1, respectively. And the degradation ratios on day 9 were 87.89 %, 86.92 %, 94.63 %, 95.49 %, 72.04 % and 82.79 %, respectively. On the 0 day after the release of lindane stress, the accumulated lindane inhibited the normal physiological activities of rice by affecting lipid metabolism in subsp. Indica BH, amino acid metabolism and synthesis and nucleotide metabolism in hybrid CY. Carbohydrate metabolism of subsp. Japonica YJ also was inhibited, but with low accumulation of lindane, YJ regulated amino acid metabolism to resist stress. With the degradation of lindane in rice, the amino acid metabolism of BH and CY, which had high degradation ratios on day 9, was activated to compound biomolecules required for the organism to recover from the damage. Amino acid metabolism and carbohydrate metabolism were disturbed and inhibited mainly in YJ with low degradation ratios. This study provides the difference of the metabolic capacity of the metabolic capacity of different rice varieties to lindane, and changes at the molecular level and metabolic response mechanism of rice during the metabolism of lindane.PMID:38184248 | DOI:10.1016/j.scitotenv.2023.169839

Clin Chim Acta. 2024 Jan 4:117752. doi: 10.1016/j.cca.2023.117752. Online ahead of print.ABSTRACTMyocarditis, an inflammatory condition of weakened heart muscles often triggered by a variety of causes, that can result in heart failure and sudden death. Novel ways to enhance our understanding of myocarditis pathogenesis is available through newer modalities (omics). In this review, we examine the roles of various biomolecules and associated functional pathways across genomics, transcriptomics, proteomics, and metabolomics in the pathogenesis of myocarditis. Our analysis further explores the reproducibility and variability intrinsic to omics studies, underscoring the necessity and significance of employing a multi-omics approach to gain profound insights into myocarditis pathogenesis. This integrated strategy not only enhances our understanding of the disease, but also confirms the critical importance of a holistic multi-omics approach in disease analysis.PMID:38184138 | DOI:10.1016/j.cca.2023.117752

J Ethnopharmacol. 2024 Jan 4:117714. doi: 10.1016/j.jep.2024.117714. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified.AIM OF THE STUDY: The objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet.MATERIALS AND METHODS: This work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics.RESULTS: JPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1β, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8.CONCLUSIONS: JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.PMID:38184027 | DOI:10.1016/j.jep.2024.117714

Cell Chem Biol. 2024 Jan 4:S2451-9456(23)00437-3. doi: 10.1016/j.chembiol.2023.12.006. Online ahead of print.ABSTRACTMethyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the β-keto acyl-CoA side chain of an ascaroside intermediate during β-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The β-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm.PMID:38183989 | DOI:10.1016/j.chembiol.2023.12.006

Plant Physiol Biochem. 2023 Dec 30;207:108324. doi: 10.1016/j.plaphy.2023.108324. Online ahead of print.ABSTRACTThree genes encoding mitochondrial uncoupling proteins (UCPs) have been described in Arabidopsis thaliana (UCP1 to UCP3). In plants, UCPs may act as an uncoupler or as an aspartate/glutamate exchanger. For instance, much of the data regarding UCP functionality were obtained for the UCP1 and UCP2 isoforms compared with UCP3. Here, to get a better understanding about the concerted action of UCP1 and UCP3 in planta, we investigated the transcriptome and metabolome profiles of ucp1 ucp3 double mutant plants during the vegetative phase. For that, 21-day-old mutant plants, which displayed the most evident phenotypic alterations compared to wild type (WT) plants, were employed. The double knockdown of UCP1 and UCP3, isoforms unequivocally present inside the mitochondria, promoted important transcriptional reprogramming with alterations in the expression of genes related to mitochondrial and chloroplast function as well as those responsive to abiotic stress, suggesting disturbances throughout the cell. The observed transcriptional changes were well integrated with the metabolomic data of ucp1 ucp3 plants. Alterations in metabolites related to primary and secondary metabolism, particularly enriched in the Alanine, Aspartate and Glutamate metabolism, were detected. These findings extend our knowledge of the underlying roles played by UCP3 in concert with UCP1 at the whole plant level.PMID:38183903 | DOI:10.1016/j.plaphy.2023.108324

Ecotoxicol Environ Saf. 2024 Jan 5;270:115936. doi: 10.1016/j.ecoenv.2024.115936. Online ahead of print.ABSTRACTNanopolystyrene (NP) and cadmium (Cd) are ubiquitous contaminants in aquatic systems. The present study aimed to investigate the toxic effects of exposure to ambient concentrations of NP and/or Cd on the intestinal tract of the Chinese mitten crab (Eriocheir sinensis). Exposure to NP and/or Cd induced oxidative stress, as evidenced by a significant increase in lipid peroxide content (LPO), total antioxidant capacity (T-AOC), and peroxidase activity (POD), and significant decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities in E. sinensis. In addition, exposure to NP and/or Cd imbalanced the homeostasis of the intestinal microbiota, as demonstrated by the significantly increased abundance of Spiroplasma. Transcriptomic and metabolomic analyses were performed to investigate the mechanisms underlying intestinal toxicity. Our results showed that ferroptosis, ABC transporters, phosphotransferase system, apoptosis, and leukocyte transendothelial migration were disturbed after exposure to NP and/or Cd. In particular, Cd exposure affected mucin type O-glycan biosynthesis, purine metabolism, and neuroactive ligand-receptor interaction. Intriguingly, co-exposure to NP and Cd might mitigate intestinal toxicity by decreasing oxidative stress and affecting these pathways. Taken together, our study clearly demonstrates that exposure to NP and/or Cd at environmentally relevant concentrations causes intestinal toxicity in E. sinensis.PMID:38183751 | DOI:10.1016/j.ecoenv.2024.115936

J Pharm Biomed Anal. 2023 Dec 29;240:115944. doi: 10.1016/j.jpba.2023.115944. Online ahead of print.ABSTRACTCurcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.PMID:38183732 | DOI:10.1016/j.jpba.2023.115944

J Pharm Biomed Anal. 2023 Nov 28;240:115884. doi: 10.1016/j.jpba.2023.115884. Online ahead of print.ABSTRACTDepression is a very common disabling mental disorder, which is typically characterized by high rates of disability and mortality. Although research into the various mechanisms of depression was still underway, its physiopathology remains uncertain. The rapid developments in new technologies and the combined use of a variety of techniques will help to understand the pathogenesis of depression and explore effective treatment methods. In this review, we focus on the combination of proteomic and metabolomic approaches to analyze metabolites and proteins in animal models of depression induced by different modeling approaches, with the aim of broadening the understanding of the physiopathological mechanisms of depression using complementary "omics" strategy.PMID:38183729 | DOI:10.1016/j.jpba.2023.115884

Environ Monit Assess. 2024 Jan 6;196(2):119. doi: 10.1007/s10661-024-12300-2.ABSTRACTArsenic (As) toxicity is an escalating problem; however, information about the metabolic events controlling the varied pattern of As accumulation in rice genotypes within their natural environment is still lacking. The present study is thus an advancement in unravelling the response of such rice genotypes. Soil-water-rice samples were analyzed for As accumulation using ICP-MS. Furthermore, we implemented metabolomics through LC-MS/MS and UHPLC to identify metabolic signatures regulating As content by observing the metalloid's composition in rice agrosystem. Results showed that rice genotypes differed significantly in their levels of metabolites, with Mini mansoori and Pioneer having the highest levels. Mini mansoori contained least As which might have been regulated by Ala, Ser, Glu, Phe, Asn, His, Ile, Lys, Gln, Trp, Tyr, chlorogenic, p-coumaric, trans-ferulic, rutin, morin, naringenin, kampferol, and myricetin, while Asp, Arg, Met, syringic, epigalocatechin, and apigenin contributed to the greater As acclimatization ability of Pioneer. Multivariate tools separated the rice genotypes into two major clusters: Pioneer-Mini mansoori and Damini-Sampoorna-Chintu. KEGG identified three major metabolic pathways (aminoacyl-tRNA, phenylpropanoid, and secondary metabolites biosynthesis route) linked with As tolerance and adaptation mechanisms in rice. Overall, these two genotypes symbolize their As hostile and accommodating attitudes probably due to the accumulated metabolites and the physicochemical attributes of the soil-water. Thus, thorough understanding of the metabolic reactions to As may facilitate the emergence of As tolerant/resilient genotypes. This will aid in the selection of molecular markers to cultivate healthier rice genotypes in As-contaminated areas.PMID:38183498 | DOI:10.1007/s10661-024-12300-2

BMC Public Health. 2024 Jan 5;24(1):98. doi: 10.1186/s12889-023-16540-8.ABSTRACTBACKGROUND: The prevalence of Type 2 Diabetes Mellitus (T2DM) in the North Africa and Middle East region is alarmingly high, prompting us to investigate the burden and factors contributing to it through the GBD study. Additionally, there is a lack of knowledge about the epidemiological status of T2DM in this region, so our aim is to provide a comprehensive overview of the burden of T2DM and its associated risk factors.METHODS: Using data from the 2019 Global Burden of Disease Study, we calculated the attributable burden of T2DM for each of the 21 countries in the region for the years 1990 and 2019. This included prevalence, mortality, disability-adjusted life years (DALYs), and risk factors.RESULTS: Between 1990 and 2019, there was a significant increase in the age-standardized incidence (79.6%; 95% Uncertainty Interval: 75.0 to 84.5) and prevalence (85.5%; [80.8 to 90.3]) rates of T2DM per 100,000 populations. The age-standardized mortality rate (1.7%; [-10.4 to 14.9]), DALYs (31.2%; [18.3 to 42.2]), and years lived with disability (YLDs) (82.6%; [77.2 to 88.1]) also increased during this period. Modifiable risk factors, such as high body mass index (56.4%; [42.8 to 69.8]), low physical activity (15.5%; [9.0 to 22.8]), and ambient particulate matter pollution (20.9%; [15.2 to 26.2]), were the main contributors to the number of deaths.CONCLUSION: The burden of T2DM, in terms of mortality, DALYs, and YLDs, continues to rise in the region. The incidence rate of T2DM has increased in many areas. The burden of T2DM attributed to modifiable risk factors continues to grow in most countries. Targeting these modifiable risk factors could effectively reduce the growth and disease burden of T2DM in the region.PMID:38183083 | DOI:10.1186/s12889-023-16540-8

Ecotoxicology. 2024 Jan 6. doi: 10.1007/s10646-023-02724-w. Online ahead of print.ABSTRACTAtlantic killifish (Fundulus heteroclitus) is a valuable model in evolutionary toxicology to study how the interactions between genetic and environmental factors serve the adaptive ability of organisms to resist chemical pollution. Killifish populations inhabiting environmental toxicant-contaminated New Bedford Harbor (NBH) show phenotypes tolerant to polychlorinated biphenyls (PCBs) and differences at the transcriptional and genomic levels. However, limited research has explored epigenetic alterations and metabolic effects in NBH killifish. To identify the involvement of epigenetic and metabolic regulation in the adaptive response of killifish, we investigated tissue- and sex-specific differences in global DNA methylation and metabolomic profiles of NBH killifish populations, compared to sensitive populations from a non-polluted site, Scorton Creek (SC). The results revealed that liver-specific global DNA hypomethylation and differential metabolites were evident in fish from NBH compared with those from SC. The sex-specific differences were not greater than the tissue-specific differences. We demonstrated liver-specific enriched metabolic pathways (e.g., amino acid metabolic pathways converged into the urea cycle and glutathione metabolism), suggesting possible crosstalk between differential metabolites and DNA hypomethylation in the livers of NBH killifish. Additional investigation of methylated gene regions is necessary to understand the functional role of DNA hypomethylation in the regulation of enzyme-encoding genes associated with metabolic processes and physiological changes in NBH populations.PMID:38182934 | DOI:10.1007/s10646-023-02724-w

Sci Rep. 2024 Jan 5;14(1):641. doi: 10.1038/s41598-024-51224-2.ABSTRACTMale infertility is one of the most common complications of diabetes mellitus (DM). Dapagliflozin is widely used to manage the type II DM. This study aimed to assess the dapagliflozin's effects on the spermatogenesis by administering either dapagliflozin (Dapa) or vehicle (db) to male db/db mice, and using littermate male db/m mice as the control (Con). We further performed the integrative analyses of the cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, and testicular proteomics. We found that dapagliflozin treatment significantly alleviated the diabetes-induced spermatogenic dysfunction by improving sperm quality, including the sperm concentration and sperm motility. The overall microbial composition was reshaped in Dapa mice and 13 species (such as Lachnospiraceae bacterium 3-1) were regarded as potential beneficial bacteria. Metabolites exhibited modified profiles, in which adenosine, cAMP, and 2'-deoxyinosine being notably altered in the cecum, plasma, and testis, respectively. Testicular protein expression patterns were similar between the Dapa and Con mice. In vivo results indicated that when compared with db group, dapagliflozin treatment alleviated apoptosis and oxidative stress in testis tissues by down-regulating 2'-deoxyinosine. This was further validated by in vitro experiments using GC-2 cells. Our findings support the potential use of dapagliflozin to prevent the diabetes-induced impaired sperm quality and to treat diabetic male infertility.PMID:38182877 | DOI:10.1038/s41598-024-51224-2

Anal Chim Acta. 2024 Jan 25;1287:342119. doi: 10.1016/j.aca.2023.342119. Epub 2023 Dec 9.ABSTRACTGlobal profiling of bile acids (BAs) is imperative for understand their function and disease pathogenesis. But it is still a challenging task, as the collision-induced dissociation (CID) fragment ions of unconjugated BAs showed low ion intensities to insufficient analysis. Herein, we developed a highly sensitive method for pseudotargeted profiling of BAs by chemical derivatization. In the developed method, a labeling reagent, 2-dimethylaminoethylamine (DMED), was adopted to label the carboxyl group of BAs. The results demonstrated that the detection sensitivities of unconjugated BAs were increased by 4-200 folds after DMED-labeling. Moreover, to profile other potential BAs not included in the 91 known targets, diverse survey experiments were performed on Qtrap-MS to search BAs for both precursor and fragment ion species, and retention index (RI) strategy was adopted to facilitate the identification of isomers. Finally, MRM-based LC-MS/MS method was validated for the pseudotargeted profiling of the BAs submetabolome with good linearity (r2 ≥ 0.990 for 89 known BAs) and high sensitivity (0.05-0.5 ng/mL for unconjugated BAs), covering unconjugated, glycine, taurine, sulfuric acid, glucuronic acid, and as well as those doubly-conjugated with above types. With this method, a total of 107 BAs, covering 54 BAs identified by authentic standards and 53 BAs candidates, were successfully determined in human serum of women with intrahepatic cholestasis of pregnancy (ICP). Multivariate analysis revealed deferentially expressed BAs. ICP disease altered the BAs profile with a reduced proportion of unconjugated, sulfate- and doubly-conjugated BAs and an increased proportion of glycine and taurine conjugates. Altered proportion and profile of BAs in ICP groups were gradually recovered during the ursodeoxycholic acid (UDCA) therapy. Overall, the strategy of DMED-labeling technique combined with diverse survey experiments is sufficiently sensitive and robust to comprehensively analysis of metabolic profiling of BAs in human serum.PMID:38182391 | DOI:10.1016/j.aca.2023.342119

Anal Chim Acta. 2024 Jan 25;1287:342117. doi: 10.1016/j.aca.2023.342117. Epub 2023 Dec 9.ABSTRACTBACKGROUND: Carbonyl-containing metabolites are a class of key intermediate in metabolism, which has potentials to be biomarkers. Since their poor ionization, derivatization reagents, such as dansylhydrazine, are usually used to improve the sensitivity and/or to facilitate quantification. However, most current carbonyl derivatization reagents only have two channels, one is isotopically labeled and the other one is non-labeled. To quantify more samples in a run and using data-independent acquisition (DIA) mode to get comprehensive and unbiased mass fragmentation, we proposed a fragment-controlled isotopic tag, called DiMe-FP-NHNH2 (FP) which has five channels: Δ0, Δ3, Δ6, Δ9, and Δ12, thus up to 5 samples can be analyzed in a run.RESULTS: The most important improvement is that the FP tag can produce multiple characteristic signals in tandem mass, diagnostic ions and neutral losses, which helps to selectively detect aldehydes/ketones for targeted and untargeted analysis. To exhibit all capabilities of the FP tag, we mimicked an untargeted metabolomics experiment, which comprises two steps. First, discovery step, using Data-Independent Analysis (SWATH-MS) and the labeling of two channels (Δ0 and Δ3), we picked out aldehyde/ketone from the pooled urine samples based on three characteristic signals, including isotope patterns, diagnostic ions, and neutral losses. Second, five-plex quantification, relative and absolute quantification were achieved in a single LC-MS analysis. Notably, because of different nominal masses, the FP tag can be used on any low or high resolution mass spectrometers.SIGNIFICANCE: The benefits and performance of the FP tag are demonstrated by the analysis of urine samples collected from patients from a prostate cancer study, in which more than a thousand features were found based on MS1 fingerprint, but only around 120 aldehyde/ketone candidates were confirmed with characteristic signals and nine of which were quantified showing significant differences from healthy and reference urine samples.PMID:38182390 | DOI:10.1016/j.aca.2023.342117

Anal Chim Acta. 2024 Jan 25;1287:342103. doi: 10.1016/j.aca.2023.342103. Epub 2023 Dec 7.ABSTRACTBACKGROUND: PLS-DA of high-dimensional metabolomics data is frequently employed to capture the most pertinent features to sample classification. But the presence of numerous insignificant input features could distort the PLS-DA model, blow up and scramble the selected differential features. Usually, univariate filtration is subsequently complemented to refine the selected features, but often giving unstable results. Whereas by precluding insignificant features through univariate data prefiltration assessed by FDR adjusted p-value, PLS-DA can generate more stable and reliable differential features. We explored and compared these two data analysis procedures to gain insights into the underlying mechanisms responsible for the disparate results.RESULTS: The effect of univariate data filtration preceding and succeeding PLS-DA analysis on the identified discriminative features/metabolites was investigated using LC-MS data acquired on the samples of human serum and C. elegans extracts, with and without metabolite standards spiked to simulate the treated and control groups of biological samples. It was shown that the univariate data prefiltration before PLS-DA usually gave less but more stable and likely more reliable and meaningful differential features, while PLS-DA applied directly to the original data could be affected by the presence of insignificant features and orthogonal noise. Large number of insignificant variables and orthogonal noise could distort the generated PLS-DA model and affect the p(corr) value, and artificially inflate the calculated VIP values of relevant features due to the increased total number of input features for model construction, thus leading to more false positives selected by the conventional VIP threshold of 1.0.SIGNIFICANCE AND NOVELTY: Univariate data filtration preceding PLS-DA was important for the identification of reliable differential features if using a conventional threshold of VIP of 1.0. Presence of insignificant features could distort the PLS-DA model and inflate VIP values. Appropriate VIP threshold is associated with the numbers of input features and the model components. For PLS-DA without univariate prefiltration, threshold of VIP larger than 1.0 is recommended for the selection of discriminative features to reduce the false positives.PMID:38182346 | DOI:10.1016/j.aca.2023.342103