PubMed

Chem Res Toxicol. 2023 Dec 7. doi: 10.1021/acs.chemrestox.3c00241. Online ahead of print.ABSTRACTEdibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.PMID:38059476 | DOI:10.1021/acs.chemrestox.3c00241

PNAS Nexus. 2023 Dec 5;2(12):pgad390. doi: 10.1093/pnasnexus/pgad390. eCollection 2023 Dec.ABSTRACTThe prevalent use of light-emitting diodes (LEDs) has caused revolutionary changes in modern life, but the potential hazards to health of blue light are poorly understood. N6-methyladenosine (m6A) is the most prevalent posttranscriptional modification in eukaryotes and can modulate diverse physiological processes by regulating mRNA fate. Here, to understand the effects and molecular mechanisms of daily low-intensity blue light exposure (BLE) and ascertain whether m6A methylation plays a role in BLE-induced phenotypes, we constructed a series of Drosophila models under different durations of daily low-intensity BLE and obtained multiomics profiles. Our results revealed that BLE could induce transcriptomic, m6A epitranscriptomic, and metabolomic reprogramming in Drosophila along with aging process. Importantly, the m6A methylation sites enriched in the 5' untranslated regions (UTRs) of Drosophila transcripts showed strong age specificity and could be altered by BLE. We experimentally validated that aging-related gene Tor and circadian rhythm-related gene per were regulated by 5' UTR-enriched m6A methylation. Overall, our study provides a systematic assessment of m6A RNA methylome reprogramming by BLE and aging in Drosophila model.PMID:38059264 | PMC:PMC10697416 | DOI:10.1093/pnasnexus/pgad390

APL Bioeng. 2023 Dec 4;7(4):046116. doi: 10.1063/5.0171109. eCollection 2023 Dec.ABSTRACTBreast cancer metastasis is initiated by invasion of tumor cells into the collagen type I-rich stroma to reach adjacent blood vessels. Prior work has identified that metabolic plasticity is a key requirement of tumor cell invasion into collagen. However, it remains largely unclear how blood vessels affect this relationship. Here, we developed a microfluidic platform to analyze how tumor cells invade collagen in the presence and absence of a microvascular channel. We demonstrate that endothelial cells secrete pro-migratory factors that direct tumor cell invasion toward the microvessel. Analysis of tumor cell metabolism using metabolic imaging, metabolomics, and computational flux balance analysis revealed that these changes are accompanied by increased rates of glycolysis and oxygen consumption caused by broad alterations of glucose metabolism. Indeed, restricting glucose availability decreased endothelial cell-induced tumor cell invasion. Our results suggest that endothelial cells promote tumor invasion into the stroma due, in part, to reprogramming tumor cell metabolism.PMID:38058993 | PMC:PMC10697723 | DOI:10.1063/5.0171109

Am J Cancer Res. 2023 Nov 15;13(11):5289-5305. eCollection 2023.ABSTRACTThis study aimed to investigate the impact of IGF2BP3, a well-known m6A modification-related protein, on the metabolic and immune microenvironment of human cervical cancer. Bioinformatics analysis was performed to analyze the expression of IGF2BP3 in various databases, and its findings were validated using human cervical cancer tissue microarrays. We conducted a study to investigate the impact of IGF2BP3 on glutamine metabolism in cervical cancer cells through the application of metabolomics and metabolic flow analysis. Additionally, we explored how cervical cancer cells promote immune escape by secreting glutamine-derived lactate in a 3D culture setting. To identify the specific targets of IGF2BP3 that influence glutamine metabolism in cervical cancer, we employed RIP-seq analysis. IGF2BP3 exhibited high expression levels in multiple cervical cancer datasets, and its expression was significantly associated with the prognosis of cervical cancer patients. In mixed 3D cell cultures of cervical cancer and T cells, IGF2BP3 was found to enhance glutamate and glutamine metabolism in cervical cancer cells by up regulating the expression of GLS and GLUD1 genes. Moreover, it influenced the differentiation of Treg cells by promoting lactate production and secretion in cervical cancer, leading to immune escape. Mechanistic analysis revealed that IGF2BP3 stabilized the mRNA of GLS and GLUD1 genes through m6A modification, thereby facilitating glutamate and glutamine metabolism in cervical cancer cells and regulating lactate production. Additionally, we investigated the correlation between GLS, GLUD1 protein expression, and IGF2BP3 expression in human cervical cancer through multicolor immunofluorescence staining. The relevance of IGF2BP3 in the context of Treg cell-associated immune escape in cervical cancer was also confirmed. IGF2BP3 exhibits high expression in human cervical cancer and plays a crucial role in stabilizing the mRNA of GLS and GLUD1 genes, key metabolic enzymes in glutamate and glutamine metabolism, through m6A modification. This process leads to immune escape in cervical cancer by promoting lactate production and secretion.PMID:38058838 | PMC:PMC10695810

Microbiome Res Rep. 2023 Jul 18;2(4):25. doi: 10.20517/mrr.2023.25. eCollection 2023.ABSTRACTMicrobiome networking analysis has emerged as a powerful tool for studying the complex interactions among microorganisms in various ecological niches, including the human body and several environments. This analysis has been used extensively in both human and environmental studies, revealing key taxa and functional units peculiar to the ecosystem considered. In particular, it has been mainly used to investigate the effects of environmental stressors, such as pollution, climate change or therapies, on host-associated microbial communities and ecosystem function. In this review, we discuss the latest advances in microbiome networking analysis, including methods for constructing and analyzing microbiome networks, and provide a case study on how to use these tools. These analyses typically involve constructing a network that represents interactions among microbial taxa or functional units, such as genes or metabolic pathways. Such networks can be based on a variety of data sources, including 16S rRNA sequencing, metagenomic sequencing, and metabolomics data. Once constructed, these networks can be analyzed to identify key nodes or modules important for the stability and function of the microbiome. By providing insights into essential ecological features of microbial communities, microbiome networking analysis has the potential to transform our understanding of the microbial world and its impact on human health and the environment.PMID:38058764 | PMC:PMC10696587 | DOI:10.20517/mrr.2023.25

Heliyon. 2023 Nov 9;9(11):e21854. doi: 10.1016/j.heliyon.2023.e21854. eCollection 2023 Nov.ABSTRACTThe effects of different processing methods on the nutritional components of sea cucumber (Apostichopus japonicus) are of concern to consumers who select sea cucumber products. This study employed liquid chromatography tandem mass spectrometry to examine the metabolites in fresh, unsoaked salted, soaked salted, and instant sea cucumber body wall samples sourced from Dalian, China. Metabolites were evaluated utilizing partial least squares discriminant analysis (PLS-DA) and subsequently subjected to KEGG metabolic pathway analysis for further investigation. PLS-DA effectively discriminated the body wall metabolites of sea cucumbers obtained via various processing techniques. The differential metabolites identified predominantly encompassed amino acids, lipids, and carbohydrates. Subsequent KEGG metabolic pathway analysis demonstrated a significant association between lipid, carbohydrate, and amino acid metabolism and the specific processing methods employed. The assessment of nutritional differences corresponding to the various A. japonicus processing methods was conducted. The findings of this study can assist in the choice of sea cucumber products and the selection of suitable processing methods.PMID:38058607 | PMC:PMC10695838 | DOI:10.1016/j.heliyon.2023.e21854

New Phytol. 2024 Jan;241(1):35-51. doi: 10.1111/nph.19369.ABSTRACTEfficient plant acclimation to changing environmental conditions relies on fast adjustments of the transcriptome, proteome, and metabolome. Regulation of enzyme activity depends on the activity of specific chaperones, chemical post-translational modifications (PTMs) of amino acid residues, and changes in the cellular and organellar microenvironment. Central to carbon assimilation, and thus plant growth and yield, Rubisco activity is regulated by its chaperone Rubisco activase (Rca) and by adjustments in the chloroplast stroma environment. Focused on crops, this review highlights the main PTMs and stromal ions and metabolites affecting Rubisco and Rca in response to environmental stimuli. Rca isoforms differ in regulatory properties and heat sensitivity, with expression changing according to the surrounding environment. Much of the physiological relevance of Rubisco and Rca PTMs is still poorly understood, though some PTMs have been associated with Rubisco regulation in response to stress. Ion and metabolite concentrations in the chloroplast change in response to variations in light and temperature. Some of these changes promote Rubisco activation while others inhibit activation, deactivate the enzyme, or change the rates of catalysis. Understanding these regulatory mechanisms will aid the development of strategies to improve carbon fixation by Rubisco under rapidly changing environments as experienced by crop plants.PMID:38058283 | DOI:10.1111/nph.19369

Cancer Cell Int. 2023 Dec 6;23(1):310. doi: 10.1186/s12935-023-03124-0.ABSTRACTThis work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells. This was accompanied by lower glycolytic and glutaminolytic activities, possibly linked to glutamine being required to increase stemness capacity and, hence, higher survival to cisplatin. The TCA cycle dynamics seemed to be time-dependent, with an apparent activation at 48 h preferentially supported by anaplerotic aromatic amino acids, leucine and lysine. A distinct behavior of leucine, compared to the other branched-chain-amino-acids, suggested the importance of the recognized relationship between leucine and in mTOR-mediated autophagy to increase resistance. Suggested markers of MDA-MB-231 TNBC cisplatin-resistance included higher phosphocreatine/creatine ratios, hypotaurine/taurine-mediated antioxidant protective mechanisms, a generalized marked depletion in nucleotides/nucleosides, and a distinctive pattern of choline compounds. Although the putative hypotheses generated here require biological demonstration, they pave the way to the use of metabolites as markers of cisplatin-resistance in TNBC and as guidance to develop therapies.PMID:38057765 | DOI:10.1186/s12935-023-03124-0

BMC Microbiol. 2023 Dec 7;23(1):389. doi: 10.1186/s12866-023-03123-1.ABSTRACTBACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted.METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro.RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells.CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.PMID:38057705 | DOI:10.1186/s12866-023-03123-1

BMC Musculoskelet Disord. 2023 Dec 6;24(1):948. doi: 10.1186/s12891-023-07094-2.ABSTRACTBACKGROUND: Recurrent lateral patellar dislocation (RLPD) poses a significant threat to patients' quality of life due to knee pain, patellofemoral cartilage damage, and potential traumatic arthritis. Predictive scoring systems have been developed to assess the risk of RLPD; however, their relative accuracy remains uncertain.PURPOSE: To investigate the accuracy of the multiple regression models to predict the individual risk of recurrent LPD.METHODS: The Patellar Instability probability calculator (PIP), Recurrent Instability of the Patella Score (RIP), and Patellar Instability Severity Score (PIS) scoring rules were measured in 171 patients with a history of patellar dislocation and 171 healthy individuals. Three prediction models were calculated based on the data to predict the risk of recurrent lateral patellar dislocation. The inter-observer and intra-observer reliability of each measurement parameter was evaluated. The predictive capacity of the three-prediction model was investigated using the receiver operating characteristic curve.RESULTS: In the case group of 171 patients, PIS accurately predicted recurrent lateral Patella dislocation in 143 patients. RIP was 96, and PIP was 83. The positive predictive values were 92.9%, 64%, and 68% respectively. In the control group of 171 patients, the PIS was validated in 160 patients who would not experience dislocations. RIP was 117, and PIP was 50. The negative predictive values were 85.1%, 60.9%, and 36.2%, respectively. The area under the curve score for the PIS was 0.866, and the RIP was 0.673. the PIP was 0.678.CONCLUSION: RIP and PIP did not work to predict LPD. PIS can accurately predict recurrent lateral patellar dislocation. It can aid doctors in making treatment decisions.LEVEL OF EVIDENCE: Level III, retrospective comparative study.PMID:38057697 | DOI:10.1186/s12891-023-07094-2

Planta. 2023 Dec 6;259(1):12. doi: 10.1007/s00425-023-04291-0.ABSTRACTTranscriptional and metabolic regulation of lignin biosynthesis and lignification plays crucial roles in Avicennia marina pneumatophore development, facilitating its adaptation to coastal habitats. Avicennia marina is a pioneer mangrove species in coastal wetland. To cope with the periodic intertidal flooding and hypoxia environment, this species has developed a complex and extensive root system, with its most unique feature being a pneumatophore with a distinct above- and below-ground morphology and vascular structure. However, the characteristics of pneumatophore lignification remain unknown. Studies comparing the anatomy among above-ground pneumatophore, below-ground pneumatophore, and feeding root have suggested that vascular structure development in the pneumatophore is more like the development of a stem than of a root. Metabolome and transcriptome analysis illustrated that the accumulation of syringyl (S) and guaiacyl (G) units in the pneumatophore plays a critical role in lignification of the stem-like structure. Fourteen differentially accumulated metabolites (DAMs) and 10 differentially expressed genes involved in the lignin biosynthesis pathway were targeted. To identify genes significantly associated with lignification, we analyzed the correlation between 14 genes and 8 metabolites and further built a co-expression network between 10 transcription factors (TFs), including 5 for each of MYB and NAC, and 23 enzyme-coding genes involved in lignin biosynthesis. 4-Coumarate-CoA ligase, shikimate/quinate hydroxycinnamoyl transferase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and peroxidase were identified to be strongly correlated with these TFs. Finally, we examined 9 key candidate genes through quantitative real-time PCR to validate the reliability of transcriptome data. Together, our metabolome and transcriptome findings reveal that lignin biosynthesis and lignification regulate pneumatophore development in the mangrove species A. marina and facilitate its adaptation to coastal habitats.PMID:38057597 | DOI:10.1007/s00425-023-04291-0

Sci Rep. 2023 Dec 6;13(1):21494. doi: 10.1038/s41598-023-48702-4.ABSTRACTFatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.PMID:38057582 | DOI:10.1038/s41598-023-48702-4

Sci Rep. 2023 Dec 6;13(1):21558. doi: 10.1038/s41598-023-49020-5.ABSTRACTTo explore the influence of wind speed on the quality of tobacco in this study, we employed a heat pump-powered intensive curing barn and a three-stage curing process. By evaluating the influence of fan parameters on the quality of tobacco leaves at different curing stages, the optimal wind speed was determined. After adopting the optimized wind speed process, the degradation of macromolecular substances was faster, the accumulation of aroma substances was delayed to 55 °C, and the accumulation was more complete. Among them, the contents of reducing sugar and total sugar in flue-cured tobacco leaves were 22.25% and 29.2%, respectively, which were lower than those in the control group. The sugar was converted into more aroma substances, and the total amount of neutral aroma substances was 48.82% higher than that of the control group. The content of related aroma substances increased significantly. The content of petroleum ether extract related to aroma substances increased by 0.93% compared with the control group. The macromolecular substances were degraded more fully than the control group, such as the starch content decreased to 1.56%. The results of metabolomics showed that the contents of aldehydes, heterocyclic compounds, alcohols, ketones and esters increased significantly in different degrees after this process. These results show that the optimization of wind speed parameters can significantly improve the baking quality of tobacco leaves. This study provides a reference for the optimization of the flue-cured tobacco baking process.PMID:38057437 | DOI:10.1038/s41598-023-49020-5

Anal Chim Acta. 2024 Jan 2;1285:342000. doi: 10.1016/j.aca.2023.342000. Epub 2023 Nov 8.ABSTRACTBACKGROUND: The increasing demand for food and feed products is stretching the capacity of the food value chain to its limits. A key step for ensuring food safety is checking for mycotoxin contamination of wheat. However, this analysis is typically performed by rather complex and expensive chromatographic methods, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS). These costly methods require extensive sample preparation that is not easily carried out at different points along the food supply chain. To overcome such challenges in sample processing, an inexpensive and portable sample preparation device was needed, that required low skill, for rapid sample-to-result mycotoxin screening.RESULTS: We describe 3D-printed and interconnectable modules for simple, integrated and on-site sample preparation, including grinding of wheat kernels, and solvent-based extraction. We characterized these 3D-printed modules for mycotoxin screening and benchmarked them against a laboratory mill using commercial lateral flow device(s) (LFD) and in-house validated LC-MS/MS analysis. Different integrated sieve configurations were compared based on grinding efficiency, and we selected a sieve size of 2 mm allowing grinding of 10 g of wheat within 5 min. Moreover, 10 first time-users were able to operate the grinder module with minimal instructions. Screening for deoxynivalenol (DON) in naturally contaminated samples at the regulatory/legal limit (1.25 mg kg-1) was demonstrated using the developed 3D-printed prototype. The whole process only takes 15 min, from sample preparation to screening result. The results showed a clear correlation (R2 = 0.96) between the LFD and LC-MS/MS.SIGNIFICANCE: Our findings demonstrate the potential of 3D-printed sample handling equipment as a valuable extension of existing analytical procedures, facilitating the on-site implementation of rapid methods for the determination of mycotoxins in grains. The presented prototype is inexpensive with material costs of 2.5€, relies on biodegradable 3D printing filament and can be produced with consumer-grade printers, making the prototype readily available. As a future perspective, the modular character of our developed tool kit will allow for adaptation to other hard food commodities beyond the determination of DON in wheat.PMID:38057054 | DOI:10.1016/j.aca.2023.342000

Int J Biol Macromol. 2023 Dec 4:128609. doi: 10.1016/j.ijbiomac.2023.128609. Online ahead of print.ABSTRACTSkeletal muscle is one the largest organs of the body and is involved in animal production and human health. Circular RNAs (circRNAs) have been implicated in skeletal myogenesis through largely unknown mechanisms. Herein, we report the phenotypic and metabolomic analysis of porcine longissimus dorsi muscles in Lantang and Landrace piglets, revealing a high-content of slow-oxidative fibers responsible for high-quality meat product in Lantang piglets. Using single-cell transcriptomics, we identified four myogenesis-related cell types, and the Akt-FoxO3 signaling axis was the most significantly enriched pathway in each subpopulation in the different pig breeds, as well as in fast-twitch glycolytic fibers. Using the multi-dimensional bioinformatic tools of circRNAome-seq and Ribo-seq, we identified a novel circRNA, circKANSL1L, with a protein-coding ability in porcine muscles, whose expression level correlated with myoblast proliferation and differentiation in vitro, as well as the transformation between distinct mature myofibers in vivo. The protein product of circKANSL1L could interact with Akt to decrease the phosphorylation level of FoxO3, which subsequently promoted FoxO3 transcriptional activity to regulate skeletal myogenesis. Our results established the existence of a protein encoded by circKANSL1L and demonstrated its potential functions in myogenesis.PMID:38056741 | DOI:10.1016/j.ijbiomac.2023.128609

Mol Metab. 2023 Dec 4:101849. doi: 10.1016/j.molmet.2023.101849. Online ahead of print.ABSTRACTOBJECTIVE: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity.METHODS: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI.RESULTS: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival.CONCLUSIONS: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.PMID:38056691 | DOI:10.1016/j.molmet.2023.101849

Sci Total Environ. 2023 Dec 4:168941. doi: 10.1016/j.scitotenv.2023.168941. Online ahead of print.ABSTRACTCoastal areas are confronted with compounding threats arising from both climatic and non-climatic stressors. Antibiotic pollution and ocean acidification are two prevalently concurrent environmental stressors. Yet their interactive effects on marine biota have not been investigated adequately and the compound hazard remain obscure. In this study, bay scallops Argopecten irradians irradians were exposed to multiple antibiotics (sulfamethoxazole, tetracycline, oxytetracycline, norfloxacin, and erythromycin, each at a concentration of 1 μg/L) combined with/without acidic seawater (pH 7.6) for 35 days. The single and interactive effects of the two stressors on A. irradians irradians were determined from multidimensional bio-responses, including energetic physiological traits as well as the molecular underpinning (metabolome and expressions of key genes). Results showed that multiple antibiotics predominantly enhanced the process of DNA repair and replication via disturbing the purine metabolism pathway. This alternation is perhaps to cope with the DNA damage induced by oxidative stress. Ocean acidification mainly disrupted energy metabolism and ammonia metabolism of the scallops, as evidenced by the increased ammonia excretion rate, the decreased O:N ratio, and perturbations in amino acid metabolism pathways. Moreover, the antagonistic effects of multiple antibiotics and ocean acidification caused alternations in the relative abundance of neurotransmitter and gene expression of neurotransmitter receptors, which may lead to neurological disorders in scallops. Overall, the revealed alternations in physiological traits, metabolites and gene expressions provide insightful information for the health status of bivalves in a natural environmental condition under the climate change scenarios.PMID:38056652 | DOI:10.1016/j.scitotenv.2023.168941

Sci Total Environ. 2023 Dec 4:169099. doi: 10.1016/j.scitotenv.2023.169099. Online ahead of print.ABSTRACTFlorfenicol (FF), an alternative veterinary antibiotic for chloramphenicol, has been widely utilized in livestock breeding to prevent and treat bacterial diseases. However, the toxicological effects of FF have yet to be fully disclosed. The domesticated silkworm (Bombyx mori), a lepidopteran model, was selected to assess the toxicological effects of FF dietary exposure with multi-omics. The findings showed that high-dose (250 μg/L) FF exposure increased the whole cocoon weight. High-dose FF exposure affected the species richness and community diversity of the microbiota in the silkworm midgut. Biochemical processes and innate immunity were impacted by FF exposure. The KEGG pathways impacted by the midgut microbiota and their metabolites were compared, and several pathways were found to be related to the two ecosystems. In addition, the innate immunity and lipid metabolism pathways were impacted, and some of the differentially expressed genes were enriched in these pathways. These related pathways may involve crosstalk between the midgut microbiota shift, midgut biological functions, and global gene expression. Therefore, our study also advances the application of the silkworm larval model in assessing antibiotic metabolic toxicity and provides novel insights into the potential risks of FF.PMID:38056650 | DOI:10.1016/j.scitotenv.2023.169099

Sci Total Environ. 2023 Dec 4:169057. doi: 10.1016/j.scitotenv.2023.169057. Online ahead of print.ABSTRACTMaintaining animal gut health through modulating the gut microbiota is a constant need when antibiotics are not used in animal feed during the food animal production process. Prebiotics is regarded as one of the most promising antibiotic alternatives for such purpose. As an attractive prebiotic, the role and mechanisms of neoagarooligosaccharides (NAOS) in promoting animal growth and gut health have not been elucidated. In this study, we first cloned and expressed marine bacterial β-agarase in yeast to optimize the NAOS preparation and then investigated the role and the underlying mechanisms of the prepared NAOS in improving chicken gut health and function. The marine bacterial β-agarase PDE13B was expressed in Pichia pastoris GS115 and generated even-numbered NAOS. Dietary the prepared NAOS promoted chicken growth and improved intestinal morphology, its barrier, and digestion capabilities, and absorption function. Metagenomic analysis indicated that NAOS modulated the chicken gut microbiota structure and function, and microbial interactions, and promoted the growth of spermidine-producing bacteria especially Faecalibacterium. Through integration of gut metagenome, gut content metabolome, and gut tissue transcriptome, we established connections among NAOS, gut microbes, spermidine, and chicken gut gene expression. The spermidine regulation of genes related to autophagy, immunity, and inflammation was further confirmed in chicken embryo intestinal epithelium cells. We also verified that NAOS can be utilized by Faecalibacterium prausnitzii to grow and produce spermidine in in vitro experiments. Collectively, we provide a systematic investigation of the role of NAOS in regulating gut health and demonstrate the microbial spermidine-mediated mechanism involved in prebiotic effects of NAOS, which lays foundation for future use of NAOS as a new antibiotic alternative in animal production.PMID:38056640 | DOI:10.1016/j.scitotenv.2023.169057

J Chromatogr A. 2023 Nov 23;1714:464527. doi: 10.1016/j.chroma.2023.464527. Online ahead of print.ABSTRACTThis study presents a novel tandem mass spectrometry (MS/MS) approach utilizing a data independent acquisition (DIA) concept specifically designed with gas chromatography-electron ionization-triple quadrupole mass spectrometry (GC-EI-QqQMS). This allows compound identification based on comparison between all the experimental MS/MS product ion spectra and the simulated library data of >1,000 MS/MS transitions of 71 compounds. The simulation data were generated by using the Competitive Fragmentation Modeling (CFM-ID) 3.0 program. The approach for calculation of the DIA MS/MS library match scores was then established and applied for identification of a range of terpenoids and oxygenated compounds in perfume. The identity of each peak was confirmed using 4-241 MS/MS transitions. The established data collection and analysis methods are expected to be useful for increased confidence in volatile compound analysis.PMID:38056391 | DOI:10.1016/j.chroma.2023.464527