PubMed

Mol Nutr Food Res. 2024 Mar 13:e2300731. doi: 10.1002/mnfr.202300731. Online ahead of print.ABSTRACTSCOPE: Gut microbiota (GM) dysbiosis and dysregulated bile acids (BAs) metabolism have been linked to ulcerative colitis (UC) pathogenesis. The possibility of utilizing live probiotics with a defined BAs-metabolizing capability to modify the composition BAs for UC treatment remains unexplored.METHODS AND RESULTS: In this study, Strain GR-4 is sourced from traditional Chinese fermented food, "Jiangshui," and demonstrated the ability to deconjugate two common conjugated BAs by over 69% and 98.47%, respectively. It administers strain GR-4 to dextran sulfate sodium (DSS)-induced UC mice, and observes an overall alleviation of UC symptoms, as evidence by improved colon morphology, reduces inflammation and oxidative stress, and restores intestinal barrier function. Importantly, these effects are reliant on an intact commensal microbiota, as depletion of GM mitigated GR-4s efficacy. Metabolomics analysis unveils a decline in conjugated BAs and an increase in secondary BAs following GR-4 administration. GM analysis indicates that GR-4 selectively enriches bacterial taxa linked to BAs metabolism, enhancing GM's capacity to modify BAs.CONCLUSION: This research demonstrates the potential for natural fermented foods and probiotics to effectively manipulate BAs composition, including conjugated and secondary BAs, to alleviate UC symptoms, underscoring the benefits of these approaches for gut health.PMID:38480985 | DOI:10.1002/mnfr.202300731

Sci Rep. 2024 Mar 13;14(1):6095. doi: 10.1038/s41598-024-55960-3.ABSTRACTIn this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.PMID:38480804 | DOI:10.1038/s41598-024-55960-3

Nat Commun. 2024 Mar 13;15(1):2268. doi: 10.1038/s41467-024-46595-z.ABSTRACTAlthough adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, and some of them exceed safe ranges. Multi-exposure models reveal significant risk effects of exposure on hyperlipidemia, metabolic syndrome and hyperuricemia. Overall, this study provides a comprehensive human serum exposome atlas and disease risk information, which can guide subsequent in-depth cause-and-effect studies between environmental exposures and human health.PMID:38480749 | DOI:10.1038/s41467-024-46595-z

Cell Death Dis. 2024 Mar 13;15(3):210. doi: 10.1038/s41419-024-06578-w.ABSTRACTIn recent years, several studies described the close relationship between the composition of gut microbiota and brain functions, highlighting the importance of gut-derived metabolites in mediating neuronal and glial cells cross-talk in physiological and pathological condition. Gut dysbiosis may affects cerebral tumors growth and progression, but the specific metabolites involved in this modulation have not been identified yet. Using a syngeneic mouse model of glioma, we have investigated the role of dysbiosis induced by the administration of non-absorbable antibiotics on mouse metabolome and on tumor microenvironment. We report that antibiotics treatment induced: (1) alteration of the gut and brain metabolome profiles; (2) modeling of tumor microenvironment toward a pro-angiogenic phenotype in which microglia and glioma cells are actively involved; (3) increased glioma stemness; (4) trans-differentiation of glioma cells into endothelial precursor cells, thus increasing vasculogenesis. We propose glycine as a metabolite that, in ABX-induced dysbiosis, shapes brain microenvironment and contributes to glioma growth and progression.PMID:38480690 | DOI:10.1038/s41419-024-06578-w

Metabolomics. 2024 Mar 13;20(2):41. doi: 10.1007/s11306-024-02090-6.ABSTRACTBACKGROUND: The National Cancer Institute issued a Request for Information (RFI; NOT-CA-23-007) in October 2022, soliciting input on using and reusing metabolomics data. This RFI aimed to gather input on best practices for metabolomics data storage, management, and use/reuse.AIM OF REVIEW: The nuclear magnetic resonance (NMR) Interest Group within the Metabolomics Association of North America (MANA) prepared a set of recommendations regarding the deposition, archiving, use, and reuse of NMR-based and, to a lesser extent, mass spectrometry (MS)-based metabolomics datasets. These recommendations were built on the collective experiences of metabolomics researchers within MANA who are generating, handling, and analyzing diverse metabolomics datasets spanning experimental (sample handling and preparation, NMR/MS metabolomics data acquisition, processing, and spectral analyses) to computational (automation of spectral processing, univariate and multivariate statistical analysis, metabolite prediction and identification, multi-omics data integration, etc.) studies.KEY SCIENTIFIC CONCEPTS OF REVIEW: We provide a synopsis of our collective view regarding the use and reuse of metabolomics data and articulate several recommendations regarding best practices, which are aimed at encouraging researchers to strengthen efforts toward maximizing the utility of metabolomics data, multi-omics data integration, and enhancing the overall scientific impact of metabolomics studies.PMID:38480600 | DOI:10.1007/s11306-024-02090-6

Planta. 2024 Mar 13;259(4):91. doi: 10.1007/s00425-024-04365-7.ABSTRACTThe article highlights omics-based interventions in sorghum to combat food and nutritional scarcity in the future. Sorghum with its unique ability to thrive in adverse conditions, has become a tremendous highly nutritive, and multipurpose cereal crop. It is resistant to various types of climatic stressors which will pave its way to a future food crop. Multi-omics refers to the comprehensive study of an organism at multiple molecular levels, including genomics, transcriptomics, proteomics, and metabolomics. Genomic studies have provided insights into the genetic diversity of sorghum and led to the development of genetically improved sorghum. Transcriptomics involves analysing the gene expression patterns in sorghum under various conditions. This knowledge is vital for developing crop varieties with enhanced stress tolerance. Proteomics enables the identification and quantification of the proteins present in sorghum. This approach helps in understanding the functional roles of specific proteins in response to stress and provides insights into metabolic pathways that contribute to resilience and grain production. Metabolomics studies the small molecules, or metabolites, produced by sorghum, provides information about the metabolic pathways that are activated or modified in response to environmental stress. This knowledge can be used to engineer sorghum varieties with improved metabolic efficiency, ultimately leading to better crop yields. In this review, we have focused on various multi-omics approaches, gene expression analysis, and different pathways for the improvement of Sorghum. Applying omics approaches to sorghum research allows for a holistic understanding of its genome function. This knowledge is invaluable for addressing challenges such as climate change, resource limitations, and the need for sustainable agriculture.PMID:38480598 | DOI:10.1007/s00425-024-04365-7

Res Synth Methods. 2024 Mar 13:e1713. doi: 10.1002/jrsm.1713. Online ahead of print.ABSTRACTMeta-analysis is a useful tool in clinical research, as it combines the results of multiple clinical studies to improve precision when answering a particular scientific question. While there has been a substantial increase in publications using meta-analysis in various clinical research topics, the number of published meta-analyses in metabolomics is significantly lower compared to other omics disciplines. Metabolomics is the study of small chemical compounds in living organisms, which provides important insights into an organism's phenotype. However, the wide variety of compounds and the different experimental methods used in metabolomics make it challenging to perform a thorough meta-analysis. Additionally, there is a lack of consensus on reporting statistical estimates, and the high number of compound naming synonyms further complicates the process. Easy-Amanida is a new tool that combines two R packages, "amanida" and "webchem", to enable meta-analysis of aggregate statistical data, like p-value and fold-change, while ensuring the compounds naming harmonization. The Easy-Amanida app is implemented in Shiny, an R package add-on for interactive web apps, and provides a workflow to optimize the naming combination. This article describes all the steps to perform the meta-analysis using Easy-Amanida, including an illustrative example for interpreting the results. The use of aggregate statistics metrics extends the use of Easy-Amanida beyond the metabolomics field.PMID:38480474 | DOI:10.1002/jrsm.1713

FEBS Open Bio. 2024 Mar 13. doi: 10.1002/2211-5463.13788. Online ahead of print.ABSTRACTHigh-fat diet (HFD)-fed mice have been widely used in the clinical investigation of obesity. However, the long-term effect of HFD on gut microbiota and metabolites, plasma and liver metabolomics, colonic and liver transcriptomics remain largely unknown. In this study, 6-week-old C57BL/6J male mice fed with HFD for 14 weeks showed increased obesity-related indexes including alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride, free fatty acids, lipopolysaccharides, IL-6, and TNFα. Furthermore, microbial diversity and richness were also significantly decreased. In the colon, genes involved in tryptophan metabolism, PPAR signaling pathway, cholesterol metabolism, and lipid localization and transport, were upregulated. While in the liver, MAPK signaling and unsaturated fatty acid biosynthesis were upregulated. Metabolomic analyses revealed decreased levels of glycerophospholipids and fatty acyl, but increased amino acids, coenzymes and vitamins, and organic acids in the colon, suggesting high absorption of oxidized lipids, while acyl-carnitine, lysophosphatidylcholine, lysophosphatidylethanolamine, and oxidized lipids were reduced in the liver, suggesting a more active lipid metabolism. Finally, correlation analyses revealed a positive correlation between gut microbiota and metabolites and the expression of genes associated with lipid localization, absorption, and transport in the colon, and nutrients and energy metabolism in the liver. Taken together, our results provide a comprehensive characterization of long-term HFD-induced obesity in mice.PMID:38479983 | DOI:10.1002/2211-5463.13788

Clin Nutr ESPEN. 2024 Apr;60:240-246. doi: 10.1016/j.clnesp.2024.02.013. Epub 2024 Feb 19.ABSTRACTBACKGROUND & AIMS: Cirrhosis is associated with insulin resistance and impaired glucose tolerance, which may be caused by impairments at different tissue levels (liver, skeletal muscle, and/or beta cell).METHODS: Here, glucose kinetics at whole-body and skeletal muscle level in patients with cirrhosis (Child-Pugh A and B) were studied during parenteral nutrition using the isotope dilution technique and arteriovenous balance approach across the leg. As opposed to the euglycemic hyperinsulinemic clamp or glucose tolerance tests applied in previous studies, this approach provides a nutrient composition more similar to a normal meal while circumventing any possible portal-systemic shunting, impaired hepatic uptake and incretin effect.RESULTS: We confirmed the presence of hepatic and peripheral insulin resistance in our patient population. Endogenous glucose production was less suppressed in response to parenteral nutrition. However, glucose uptake in skeletal muscle was increased.CONCLUSION: Our results suggests that in our study participants with cirrhosis, the hepatic and peripheral insulin resistance is compensated for by increased insulin secretion and thus, increased glucose uptake in muscle. Hereby, glucose homeostasis is maintained.PMID:38479917 | DOI:10.1016/j.clnesp.2024.02.013

Funct Plant Biol. 2024 Mar 14. doi: 10.1071/FP22190. Online ahead of print.ABSTRACTPugionium cornutum is an annual or biennial xerophyte distributed in arid regions, with drought resistance properties. While previous studies have predominantly focused on the physiological changes of P. cornutum, the understanding of its metabolite variations remains limited. In this study, untargeted metabolomic technology was performed to analyse the change of metabolites in the roots of P. cornutum seedlings under drought stress. Our findings revealed that compared to the R1, the root water potential and the number of lateral roots increased, while the length of the tap root and fresh weight increased first and then decreased. In the R1-R2, a total of 45 differential metabolites (DMs) were identified, whereas in the R1-R3 82 DMs were observed. Subsequently, KEGG analysis revealed a significant enrichment of microbial metabolism in diverse environments and aminobenzoate degradation in the R1-R2, and phenylpropanoid biosynthesis, ubiquinone, and other terpenoid-quinone biosynthesis and isoquinoline alkaloid biosynthesis were significantly enriched in the R1-R3. The upregulation DMs, including L-arginosuccinate, L-tyrosine, p-coumarate, caffeate, ferulate, vanillin, coniferin, 5-aminopentanoate, 2-methylmaleate and 2-furoate in P. cornutum seedlings may play a crucial role in enhancing root growth and improving drought resistance. These findings provide a basis for future investigations into the underlying mechanisms of drought resistance in P. cornutum.PMID:38479792 | DOI:10.1071/FP22190

Toxicology. 2024 Mar 11:153772. doi: 10.1016/j.tox.2024.153772. Online ahead of print.ABSTRACTVanadium pentoxide (V+5) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V+5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V+5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D3, and drug metabolism, without causing cell death. Altered mitochondrial structure and function, and disruption in glycolysis were observed with as low as 0.01 ppm (0.2 μM) V+5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V+5 treatment, supporting potential toxicity of V+5 at low levels. Taken together, the present study shows that V+5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death.PMID:38479551 | DOI:10.1016/j.tox.2024.153772

Cell Host Microbe. 2024 Mar 8:S1931-3128(24)00054-4. doi: 10.1016/j.chom.2024.02.011. Online ahead of print.ABSTRACTChikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.PMID:38479396 | DOI:10.1016/j.chom.2024.02.011

Cell Host Microbe. 2024 Mar 8:S1931-3128(24)00057-X. doi: 10.1016/j.chom.2024.02.014. Online ahead of print.ABSTRACTPlant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis. Root metabolite profiling of each segment reveals differential metabolite enrichment and specificity. Bioinformatic analyses and GUS histochemistry indicate microbe-induced accumulation of SWEET2, 4, and 12 sugar uniporters. Profiling of root segments from sweet mutants shows altered spatial metabolic profiles and reorganization of endospheric root microbiota. This work reveals the interdependency between root metabolites and microbial colonization and the contribution of SWEETs to spatial diversity and stability of microbial ecosystem.PMID:38479394 | DOI:10.1016/j.chom.2024.02.014

Phytomedicine. 2024 Feb 28;128:155492. doi: 10.1016/j.phymed.2024.155492. Online ahead of print.ABSTRACTBACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored.PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms.METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice.RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells.CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.PMID:38479258 | DOI:10.1016/j.phymed.2024.155492

Theriogenology. 2024 Mar 7;220:56-69. doi: 10.1016/j.theriogenology.2024.03.002. Online ahead of print.ABSTRACTMetabolic coupling between oocytes and the surrounding somatic cells allows for normal two-way communication, and their interactions is necessary for generating developmentally competent eggs. However, the metabolic framework that support oocyte maturation in surrounding cumulus cells is still lacking. Herin, we established a temporal metabolome profile of porcine cumulus cells at three key stages during oocyte maturation, illustrating the picture of global metabolic network in cumulus cells. Importantly, we discovered the novel metabolic signature in cumulus cells during meiotic maturation, in specific, significant consumption of fatty acids, elevated activity of hexosamine biosynthetic pathway (HBP), and enhanced polyamine biosynthesis. Meanwhile, we observed the different utilization of tryptophan, active biosynthesis of progesterone, and progressive decrease in purine and pyrimidine metabolism as the oocytes progress through meiosis. Collectively, our metabolomic data serves an entree to elaborate on the dynamic changes in these metabolic pathways, which not only reveals the metabolic networks controlling oocyte development, but also lays a foundation for the discovery of biomarkers in the improvement in porcine oocyte culture system.PMID:38479090 | DOI:10.1016/j.theriogenology.2024.03.002

Talanta. 2024 Feb 25;273:125826. doi: 10.1016/j.talanta.2024.125826. Online ahead of print.ABSTRACTPrimary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (1H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers. A classification model, based on the metabolomic fingerprint in tears was generated as a non-invasive tool to support the preclinical and clinical POAG diagnosis. 1H NMR spectra were acquired from 30 tear samples corresponding to the POAG group (n = 11) and the control group (n = 19). Data were analysed by multivariate statistics (partial least squares-discriminant analysis: PLS-DA) to determine a model capable of differentiating between groups. The whole data set was split into calibration (65%)/validation (35%), to test the performance and the ability for glaucoma discrimination. The calculated PLS-DA model showed an area under the curve (AUC) of 1, as well as a sensitivity of 100% and a specificity of 83.3% to distinguish POAG group versus control group tear data. This model included 11 metabolites, potential biomarkers of the disease. When comparing the study groups, a decrease in the tear concentration of phenylalanine, phenylacetate, leucine, n-acetylated compounds, formic acid, and uridine, was found in the POAG group. Moreover, an increase in the tear concentration of taurine, glycine, urea, glucose, and unsaturated fatty acids was observed in the POAG group. These results highlight the potential of tear metabolomics by 1H NMR spectroscopy as a non-invasive approach to support early POAG diagnosis and in order to prevent visual loss.PMID:38479028 | DOI:10.1016/j.talanta.2024.125826

Environ Sci Technol. 2024 Mar 13. doi: 10.1021/acs.est.3c10132. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA), the most extensively utilized brominated flame retardant, has raised growing concerns regarding its environmental and health risks. Neurovascular formation is essential for metabolically supporting neuronal networks. However, previous studies primarily concerned the neuronal injuries of TBBPA, its impact on the neurovascularture, and molecular mechanism, which are yet to be elucidated. In this study, 5, 30, 100, 300 μg/L of TBBPA were administered to Tg (fli1a: eGFP) zebrafish larvae at 2-72 h postfertilization (hpf). The findings revealed that TBBPA impaired cerebral and ocular angiogenesis in zebrafish. Metabolomics analysis showed that TBBPA-treated neuroendothelial cells exhibited disruption of the TCA cycle and the Warburg effect pathway. TBBPA induced a significant reduction in glycolysis and mitochondrial ATP production rates, accompanied by mitochondrial fragmentation and an increase in mitochondrial reactive oxygen species (mitoROS) production in neuroendothelial cells. The supplementation of alpha-ketoglutaric acid, a key metabolite of the TCA cycle, mitigated TBBPA-induced mitochondrial damage, reduced mitoROS production, and restored angiogenesis in zebrafish larvae. Our results suggested that TBBPA exposure impeded neurovascular injury via mitochondrial metabolic perturbation mediated by mitoROS signaling, providing novel insight into the neurovascular toxicity and mode of action of TBBPA.PMID:38478874 | DOI:10.1021/acs.est.3c10132

Plant Physiol. 2024 Mar 13:kiae149. doi: 10.1093/plphys/kiae149. Online ahead of print.ABSTRACTManipulation of gene expression is central to understanding gene function, engineering cell behavior, and altering biological traits according to production demands. Nuclease-dead Cas9 (dCas9), a variant of active Cas9, offers a versatile platform for the precise control of genome function without DNA cleavage. Notably, however, an effective and universal dCas9-based transcriptional repression system remains unavailable in plants. The non-canonical histone acetyltransferase TENDRIL-LESS (CsTEN) is responsible for chromatin loosening and histone modification in cucumber (Cucumis sativus). In this study, we engineered a gene regulation tool by fusing TEN and its truncated proteins with dCas9. The full-length dCas9-TEN protein substantially repressed gene expression, with the N-terminal domain identified as the core repression domain. We subsequently validated the specificity and efficacy of this system through both transient infection and genetic transformation in cucumber and Arabidopsis (Arabidopsis thaliana). Electrophoretic mobility shift assay (EMSA) revealed the ability of the N-terminal domain of TEN to bind to chromatin, which may promote target binding of the dCas9 complex and enhance the transcriptional repression effect. Our tool enriches the arsenal of genetic regulation tools available for precision breeding in crops.PMID:38478589 | DOI:10.1093/plphys/kiae149

Iran J Allergy Asthma Immunol. 2023 Dec 28;22(6):536-550. doi: 10.18502/ijaai.v22i6.14643.ABSTRACTMicroRNAs (miRs) play a role in several diseases, such as rheumatoid arthritis (RA). The purpose of this study was to discover new microRNAs and investigate their involvement in RA, examining their connections with inflammation and metabolic markers. New microRNAs related to RA were predicted using Mirbase and TargetScan databases based on RA target genes. The relationships between miRNAs and targets were visualized with Cytoscape software. Real-time polymerase chain reaction confirmed detectable miRNAs and metabolic factors were assessed using immunoassay and spectrometry methods in RA patients and healthy subjects. Four microRNAs (hsa-miR-153-5p, hsa-miR-4270, hsa-miR-4441, and hsa-miR-6754-5p) showed the highest correlation with RA target genes among millions of microRNAs. The expression of miR-146b (fold change=1.8) and miR-4441 (fold change=1.7) was notably reduced, while miR-4270 showed upregulation (fold change=1.8) in plasma from RA patients compared to healthy individuals. MiR-6754 exhibited a decrease (fold change=1.3) but was statistically insignificant. MiR-153-5p expression was undetectable in plasma. Receiver operating characteristic (ROC) curve analysis indicated that miR-4441, with an area under the ROC curve (AUC) of 0.7728, and miR-4270 (AUC=0.7353) were promising biomarkers for RA. The expression of these studied miRNAs significantly correlated with essential clinical characteristics, including liver enzymes, cholesterol, phosphorus, and vitamin D3. Our findings suggest that miR-4270 and miR-4441, present in the circulation, exhibit distinct expression patterns in RA. These microRNAs may serve as links between inflammation and metabolism and represent promising new biomarkers for this disease.PMID:38477951 | DOI:10.18502/ijaai.v22i6.14643

Proteomics. 2024 Mar 13:e2300160. doi: 10.1002/pmic.202300160. Online ahead of print.ABSTRACTIntestinal ischemia-reperfusion injury (IR) is implicated in various clinical conditions and causes damage to the intestinal epithelium resulting in intestinal barrier loss. This presents a substantial clinical challenge, emphasizing the importance of gaining a comprehensive understanding of molecular events to aid in the identification of novel therapeutic targets. This review systematically explores the extent to which omics technologies-transcriptomics, proteomics, metabolomics, and metagenomics-have already contributed to deciphering the molecular mechanisms contributing to intestinal IR injury, in in vivo and in vitro animal and human models, and in clinical samples. Recent breakthroughs involve applying omics methodologies on exosomes, organoids, and single cells, shedding light on promising avenues and valuable targets to reduce intestinal IR injury. Future directions aimed at expediting clinical translation are discussed as well and include multi-omics data integration to facilitate the identification of key regulatory nodes driving intestinal IR injury and advancing human organoid models based on the novel insights by single-cell omics technologies, offering hope for clinical application of therapeutic strategies in the years to come.PMID:38477684 | DOI:10.1002/pmic.202300160