PubMed

Aquat Toxicol. 2023 Nov 8;265:106760. doi: 10.1016/j.aquatox.2023.106760. Online ahead of print.ABSTRACTThe incorrect use of antibiotics and pesticides poses significant risks of biological toxicity. Their simultaneous exposure could jeopardize fish health and hinder sustainable aquaculture. Here, we subjected grass carp to waterborne cypermethrin (0.65 μg/L) or/and sulfamethoxazole (0.30 μg/L) treatments for a duration of 6 weeks. We closely monitored the effects on intestinal function, the intestinal microbiome, and the liver metabolome. The results revealed that exposure to waterborne cypermethrin or/and sulfamethoxazole compromised intestinal barrier function and decreased the expression of intestinal tight junction proteins. Additionally, heightened levels of pro-inflammatory cytokines in the intestines and reduced antioxidant levels indicated systemic inflammation and oxidative stress, with more severe effects observed in the combined exposure group. 16S rRNA sequencing of intestinal tissues suggested Firmicutes play a key role in the intestinal microbiota. GC/MS metabolomics of the liver showed more differential metabolites (56) in the co-exposure group compared to cypermethrin (45) or sulfamethoxazole (32) alone, indicating greater toxicological effects with combined exposure. Our analyses also suggest that ATP-binding cassette transporters could serve as a novel endpoint for assessing the risk of pesticide and antibiotic mixtures in grass carp. In summary, this study underscores the potential ecological risks posed by antibiotics and pesticides to aquatic environments and products. It emphasizes the importance of the gut-liver axis as a comprehensive pathway for assessing the toxicity in fish exposed to environmental contaminants.PMID:37977013 | DOI:10.1016/j.aquatox.2023.106760

J Pharm Biomed Anal. 2023 Oct 27;238:115814. doi: 10.1016/j.jpba.2023.115814. Online ahead of print.ABSTRACTOBJECTIVE: Cisplatin (CDDP) has been widely used for chemotherapy against tumours. However，the nephrotoxicity has limited its clinical use. Here, we reported a novel compound, Capilliposide A (CPS-A), to exhibit therapeutic effects on CDDP-induced acute kidney injury (AKI) and explored its potential mechanisms via transcriptome and metabolome.MATERIALS AND METHODS: HK-2 cells were treated with CPS-A, after which cell viability, apoptosis and inflammation were investigated. A mouse model of AKI was constructed by single injection of CDDP in vivo. The renal function and morphology and mitochondrial function were assessed by pathological section and transmission electron microscope (TEM). Transcriptomics and metabolomics are used to explore possible mechanisms which was later verified in vitro.RESULTS: CPS-A administration improved the survival rates of HK-2 cells with a significant decrease in the expression of KIM-1, NGAL, IL-6, IL-8 and IL-1β. In vivo results also suggested that CPS-A attenuates CDDP-induced kidney injury by reducing serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Furthermore, TEM also showed the improvement of mitochondrial ultrastructure both in vivo and vitro. Transcriptomics analysis of the mice's renal cortex indicated the expression of ATF4 and CHOP were upregulated, which was further validated by qPCR and Western blotting in vitro. Integrative analysis of transcriptome and metabolome indicated that L-Leucine enriched in Valine, leucine and isoleucine degradation might be potential targets.CONCLUSIONS: CPS-A can effectively regulate endogenous metabolites associated with amino acid metabolism and ameliorate apoptosis and oxidative stress in CDDP-induced AKI by reducing endoplasmic reticulum stress.PMID:37976990 | DOI:10.1016/j.jpba.2023.115814

J Chromatogr A. 2023 Nov 11;1713:464505. doi: 10.1016/j.chroma.2023.464505. Online ahead of print.ABSTRACTAnalysis of exposure to traditional Chinese medicine (TCM) in vivo based on mass spectrometry is helpful for the screening of effective ingredients of TCM and the development of new drugs. The method of screening biomarkers through metabolomics technology is a nontargeted research method to explore the differential components between two sets of biological samples. By taking this advantage, this study aims to takes Forsythia suspensa, which is a TCM also known as Lian Qiao (LQ), as the research object and to study its in vivo exposure by using metabolomics technology. By comparing the significant differences between biological samples before and after administration, it could be focused on the components that were significantly upregulated, where a complete set of analysis strategies for nontargeted TCM in vivo exposure mass spectrometry was established. Furthermore, the threshold parameters for peak extraction, parameter selection during statistical data analysis, and sample concentration multiples in this method have also been optimized. More interestingly, by using the established analysis strategy, we found 393 LQ-related chemical components in mice after administration, including 102 prototypes and 291 LQ-related metabolites, and plotted their metabolic profiles in vivo. In short, this study has obtained a complete mass spectrum of LQ exposure in mice in vivo for the first time, which provides a reference for research on the active ingredients of LQ in vivo. More importantly, compared with other methods, the analysis strategy of nontargeted exposure of TCM in vivo-based mass spectrometry, constructed by using this research method, has good universality and does not require self-developed postprocessing software. It is worth mentioning that, for the identification and characterization of trace amounts of metabolites in vivo, this analysis strategy has no discrimination and has a detection capability similar to that of highly exposed components.PMID:37976901 | DOI:10.1016/j.chroma.2023.464505

Phytomedicine. 2023 Oct 18;123:155154. doi: 10.1016/j.phymed.2023.155154. Online ahead of print.ABSTRACTOBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model.METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins.RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFβ1, p-SMAD3, collagen III, Gq and PLCβ1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB.CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFβ1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCβ1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.PMID:37976696 | DOI:10.1016/j.phymed.2023.155154

Phytomedicine. 2023 Nov 8;123:155201. doi: 10.1016/j.phymed.2023.155201. Online ahead of print.ABSTRACTBACKGROUND: Astragali Radix (AR) is a widely used herbal medicine. The quality of AR is influenced by several key factors, including the production area, growth mode, species, and grade. However, the markers currently used to distinguish these factors primarily focus on secondary metabolites, and their validation on large-scale samples is lacking.PURPOSE: This study aims to discover reliable markers and develop classification models for identifying the production area, growth mode, species, and grade of AR.METHODS: A total of 366 batches of AR crude slices were collected from six provinces in China and divided into learning (n = 191) and validation (n = 175) sets. Three ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for determining 22 primary and 10 secondary metabolites in AR methanol extract. Based on the quantification data, seven machine learning algorithms, such as Nearest Neighbors and Gradient Boosted Trees, were applied to screen the potential markers and build the classification models for identifying the four factors associated with AR quality.RESULTS: Our analysis revealed that secondary metabolites (e.g., astragaloside IV, calycosin-7-O-β-D-glucoside, and ononin) played a crucial role in evaluating AR quality, particularly in identifying the production area and species. Additionally, fatty acids (e.g., behenic acid and lignoceric acid) were vital in determining the growth mode of AR, while amino acids (e.g., alanine and phenylalanine) were helpful in distinguishing different grades. With both primary and secondary metabolites, the Nearest Neighbors algorithm-based model was constructed for identifying each factor of AR, achieving good classification accuracy (>70%) on the validation set. Furthermore, a panel of four metabolites including ononin, astragaloside II, pentadecanoic acid, and alanine, allowed for simultaneous identification of all four factors of AR, offering an accuracy of 86.9%.CONCLUSION: Our findings highlight the potential of integrating large-scale targeted metabolomics and machine learning approaches to accurately identify the quality-associated factors of AR. This study opens up possibilities for enhancing the evaluation of other herbal medicines through similar methodologies, and further exploration in this area is warranted.PMID:37976693 | DOI:10.1016/j.phymed.2023.155201

Blood. 2023 Nov 17:blood.2023022052. doi: 10.1182/blood.2023022052. Online ahead of print.ABSTRACTIn the field of Transfusion Medicine, the clinical relevance of the metabolic markers of the red blood cell (RBC) storage lesion is incompletely understood. Here we performed metabolomics of RBC units from 643 donors enrolled in the Recipient Epidemiology and Donor Evaluation Study - REDS RBC Omics. These units were tested at storage day 10, 23 and 42 for a total of 1,929 samples, and also characterized for end of storage hemolytic propensity following oxidative and osmotic insults. Our results indicate that the metabolic markers of the storage lesion poorly correlated with hemolytic propensity. On the other hand, kynurenine was not affected by storage duration and was identified as the top predictor of osmotic fragility. RBC kynurenine levels were affected by donor age and BMI, and were reproducible within the same donor across multiple donations 2-12 months apart. To delve into the genetics underpinnings of kynurenine levels in stored RBCs, we thus tested kynurenine levels in day 42 stored RBCs from 13,091 donors from the REDS RBC Omics study, a population that was also genotyped for 879,000 single nucleotide polymorphisms. Through a metabolite Quantitative Trait Loci analysis, we identified polymorphisms in SLC7A5, ATXN2 and a series of rate-limiting enzymes (e.g., IDO1, KMO, TDO) in the kynurenine pathway as critical factors impacting RBC kynurenine levels. By interrogating a donor-recipient linkage vein-to-vein database, we then report that SLC7A5 polymorphisms are also associated with changes in hemoglobin and bilirubin levels suggestive of in vivo hemolysis in 4,470 critically-ill recipients receiving single unit transfusions.PMID:37976448 | DOI:10.1182/blood.2023022052

J Agric Food Chem. 2023 Nov 17. doi: 10.1021/acs.jafc.3c06399. Online ahead of print.ABSTRACTEmbryogenic cultures of longan (Dimocarpus longan Lour.) contain various metabolites with pharmacological properties that may function in the regulation of somatic embryogenesis (SE). In this study, based on widely targeted metabolomics, 501 metabolites were obtained from the embryogenic calli, incomplete compact proembryogenic cultures, and globular embryos during early SE of longan, among which 41 flavonoids were differentially accumulated during the SE. Using RNA sequencing, 36 flavonoid-biosynthesis-related genes and 43 MYB and 52 bHLH transcription factors were identified as differentially expressed genes. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the flavonoid metabolism-related pathways were significantly enriched during the early SE. These results suggested that the changes in flavonoid levels in the embryogenic cultures of longan were mediated by MYBs and bHLHs via regulating flavonoid-biosynthesis-related genes, thus potentially regulating early SE. The identified metabolites in the embryogenic cultures of longan can be used to develop pharmaceutical ingredients.PMID:37976371 | DOI:10.1021/acs.jafc.3c06399

Anal Chem. 2023 Nov 17. doi: 10.1021/acs.analchem.3c01094. Online ahead of print.ABSTRACTFeature-based molecular networking (FBMN) is a powerful analytical tool for mass spectrometry (MS)-based untargeted metabolomics data analysis. FBMN plays an important role in drug metabolism studies, enabling the visualization of complex metabolomics data to achieve metabolite characterization. In this study, we propose a strategy for the characterization of glutathione (GSH) adducts formed via in vitro metabolic activation using FBMN assisted by multivariate analysis (MVA). Acetaminophen was used as a model substrate for method development, and the practical potential of the method was investigated by its application to 2-aminophenol (2-AP) and 2,4-dinitrochlorobenzene (DNCB). Two 2-AP GSH adducts and one DNCB GSH adduct were successfully characterized by forming networks with GSH even though the mass spectral information obtained for the parent compound was deficient. False positives were effectively filtered out by the variable influence on projection cutoff criteria obtained from orthogonal partial least-squares-discriminant analysis. The GSH adducts formed by enzymatic or nonenzymatic reactions were intuitively distinguished by the pie chart of FBMN results. In summary, our approach effectively characterizes GSH adducts, which serve as compelling evidence of bioactivation. It can be widely utilized to enhance risk assessment in the context of drug metabolism.PMID:37976220 | DOI:10.1021/acs.analchem.3c01094

Diabetes. 2023 Nov 17:db230368. doi: 10.2337/db23-0368. Online ahead of print.ABSTRACTEndothelial cells (EC) play essential roles in retinal vascular homeostasis. This study aimed to characterize retinal EC heterogeneity and functional diversity using single-cell RNA sequencing. Systematic analysis of cellular compositions and cell-cell interaction networks identified a unique EC cluster with high inflammatory gene expression in diabetic retina; sphingolipid metabolism is a prominent aspect correlated with changes in retinal function. Among sphingolipid-related genes, alkaline ceramidase 2 (ACER2) showed the most significant increase. Plasma samples of patients with non-proliferative diabetic retinopathy (NPDR) with or without diabetic macular edema (DME) and active PDR were collected for mass spectrometry analysis. Metabolomic profiling revealed that the ceramide levels were significantly elevated in NPDR-NDME/DME and further increased in active PDR compared with control patients. In vitro analyses showed that ACER2 overexpression retarded endothelial barrier breakdown induced by ceramide, while silencing of ACER2 further disrupted the injury. Moreover, intravitreal injection of the recombinant ACER2 adeno-associated virus rescued diabetes-induced vessel leakiness, inflammatory response, and neurovascular disease in diabetic mouse models. Together, this study revealed a new diabetes-specific retinal EC population and a negative feedback regulation pathway that reduces ceramide content and endothelial dysfunction by upregulating ACER2 expression. These findings provide insights into cell-type targeted interventions for diabetic retinopathy.PMID:37976214 | DOI:10.2337/db23-0368

Plant Signal Behav. 2023 Dec 31;18(1):2283363. doi: 10.1080/15592324.2023.2283363. Epub 2023 Nov 17.ABSTRACTPepino (Solanum muricatum), a horticultural crop that has experienced significant growth in the highlands of China over the past two decades, is widely embraced by consumers due to its distinctive taste and nutritional advantages. This study focused on the cultivar 'Qingcanxiang' of pepino grown on the Qinghai-Tibetan Plateau was analyzed using UPLC-QTOF-MS and RNA-seq transcriptome sequencing. Fruit samples were collected at three distinct stages of development, and the results of the metabolomics and transcriptomics were compared and correlated. The study's findings indicate that the 'Qingcanxiang' fruit contained a total of 187 metabolites, comprising 12 distinct categories of compounds, including amino acids and their derivatives, organic acids, sugars and alcohols, phenols and phenolic acids. Of these metabolites, 94 were identified as differential. Significant variations in nutrient composition were observed across the three growth stages of the fruit. Specifically, the stage spanning from the growth to the maturation was identified as the critical stages for nutrient accumulation and flavor development. Transcriptome sequencing analysis revealed a set of highly associated genes between aspartate and quinic acid, namely SIR2, IRAK4, RP-L29, and CCNH. These genes are potentially involved in the regulation of both amino acid and phenolic acid synthesis. Through the application of metabolomics and transcriptomics, this investigation elucidates the alterations in metabolites and the underlying molecular regulatory mechanisms of pepino fruits during three growth stages. The findings furnish a theoretical foundation for the evaluation of nutritional quality and the enhancement of breeding strategies for pepino.PMID:37976083 | DOI:10.1080/15592324.2023.2283363

J Neurooncol. 2023 Nov 17. doi: 10.1007/s11060-023-04508-y. Online ahead of print.ABSTRACTPURPOSE: Primary brain tumors are a leading cause of cancer-related death in children, and medulloblastoma is the most common malignant pediatric brain tumor. The current molecular characterization of medulloblastoma is mainly based on protein-coding genes, while little is known about the involvement of long non-coding RNAs (lncRNAs). This study aimed to elucidate the role of the lncRNA OTX2-AS1 in medulloblastoma.METHODS: Analyses of DNA copy number alterations, methylation profiles, and gene expression data were used to characterize molecular alterations of OTX2-AS1 in medulloblastoma tissue samples. In vitro analyses of medulloblastoma cell models and orthotopic in vivo experiments were carried out for functional characterization of OTX2-AS1. High-throughput drug screening was employed to identify pharmacological inhibitors, while proteomics and metabolomics analyses were performed to address potential mechanisms of drug action.RESULTS: We detected amplification and consecutive overexpression of OTX2 and OTX2-AS1 in a subset of medulloblastomas. In addition, OTX2-AS1 promoter methylation was linked to OTX2-AS1 expression. OTX2-AS1 knockout reduced medulloblastoma cell viability and cell migration in vitro and prolonged survival in the D283 orthotopic medulloblastoma mouse xenograft model. Pharmacological inhibition of BCL-2 suppressed the growth of OTX2-AS1 overexpressing medulloblastoma cells in vitro.CONCLUSIONS: Our study revealed a pro-tumorigenic role of OTX2-AS1 in medulloblastoma and identified BCL-2 inhibition as a potential therapeutic approach to target OTX2-AS1 overexpressing medulloblastoma cells.PMID:37976029 | DOI:10.1007/s11060-023-04508-y

Metabolomics. 2023 Nov 17;19(12):94. doi: 10.1007/s11306-023-02056-0.ABSTRACTINTRODUCTION: Idiopathic acquired aplastic anemia (AA) is a bone marrow failure disorder where aberrant T-cell functions lead to depletion of hematopoietic stem and progenitor cells in the bone marrow (BM) microenvironment. T-cells undergo metabolic rewiring, which regulates their proliferation and differentiation. Therefore, studying metabolic variation in AA patients may aid us with a better understanding of the T-cell regulatory pathways governed by metabolites and their pathological engagement in the disease.OBJECTIVE: To identify the differential metabolites in BM plasma of AA patients, AA follow-up (AAF) in comparison to normal controls (NC) and to identify potential disease biomarker(s).METHODS: The study used 1D 1H NMR Carr-Purcell-Meiboom-Gill (CPMG) spectra to identify the metabolites present in the BM plasma samples of AA (n = 40), AAF (n = 16), and NC (n = 20). Metabolic differences between the groups and predictive biomarkers were identified by using multivariate analysis and receiver operating characteristic (ROC) module of Metaboanalyst V5.0 tool, respectively.RESULTS: The AA and AAF samples were well discriminated from NC group as per Principal Component analysis (PCA). Further, we found significant alteration in the levels of 17 metabolites in AA involved in amino-acid (Leucine, serine, threonine, phenylalanine, lysine, histidine, valine, tyrosine, and proline), carbohydrate (Glucose, lactate and mannose), fatty acid (Acetate, glycerol myo-inositol and citrate), and purine metabolism (hypoxanthine) in comparison to NC. Additionally, biomarker analysis predicted Hypoxanthine and Acetate can be used as a potential biomarker.CONCLUSION: The study highlights the significant metabolic alterations in the BM plasma of AA patients which may have implication in the disease pathobiology.PMID:37975930 | DOI:10.1007/s11306-023-02056-0

Metabolomics. 2023 Nov 17;19(12):95. doi: 10.1007/s11306-023-02057-z.ABSTRACTINTRODUCTION: The prevalence of hypertension and obesity are a worldwide concern.OBJETIVES: Assess the metabolites profile after intervention with mixed dietary fiber in overweight and obese normotensive women.METHODS: This is a randomized double blind placebo-controlled study. Through a simple randomization process, two groups were allocated, with eleven women (group 1) receiving 12 g of mixed dietary fiber and thirteen women (group 2) receiving 12 g of placebo (corn starch) for eight weeks. Anthropometric and biochemical tests and lifestyle were analyzed. As for evaluation metabolomics, used a 1H NMR. The data matrix generated 96 samples and 225 variables, which was exported in the ASCII format for the "The Unscrumbler" statistics software (version 9.7, CAMO Process).RESULTS: After the intervention with mixed dietary fiber, significant differences were observed between the main types of metabolites, referring to the increase in the relative peak areas of in three HDL metabolites 4.94 ppm (0.0086*), HDL 1.28 ppm (0 .0337*), HDL 0.88 ppm (0.0224*) and an α-glucose metabolite 4.90 ppm (0.0106) and the reduction in systolic blood pressure (SBP) (0.0292*) of 7 mmHg in the reference range and in the placebo group there was a reduction in SBP (0.0118*) of 4 mmHg and of a choline metabolite 3.65 ppm (0.0266*), which does not call into question the validity of these results in the literature.CONCLUSION: The synergism of the functions of these statistically highlighted metabolites contributed to prevention the increase in SBP after fiber intervention in overweight and obese normotensive women.PMID:37975928 | DOI:10.1007/s11306-023-02057-z

J Oral Facial Pain Headache. 2023 Nov 17;37(3):207-216. doi: 10.11607/ofph.3353.ABSTRACTAIMS: To develop a new approach to provide insights into contributing factors to the etiology and pathogenesis of temporomandibular disorders (TMDs) through discrimination of the salivary metabolomic profiling of patients with TMDs of muscular origin (ie, local myalgia) and healthy individuals.METHODS: Saliva samples from 19 patients with TMDs of muscular origin (ie, local myalgia) and 39 healthy controls were collected and identified by nuclear magnetic resonance (NMR) spectroscopy. 1H NMR spectra for all samples were acquired using a Bruker Avance-III NMR spectrometer operating at 500 MHz, and data processing was performed in TopSpin, MestreNova, SIMCA, and AMIX softwares for metabolite identification.RESULTS: Eight key metabolites were identified between the healthy controls and patients: L-isoleucine, methylmalonic acid, isopropanolamine, dimethyl sulfone, lactic acid, 4-ethoxyphenylacetic acid, N-acetyl alanine, and D-galactose.CONCLUSIONS: The results of this study demonstrate that NMR-based metabolomics coupled with multivariate data analysis is a powerful method for the metabolomic profiling of patients with TMDs of muscular origin (ie, local myalgia).PMID:37975784 | DOI:10.11607/ofph.3353

J Diabetes Metab Disord. 2023 Sep 23;22(2):1801-1804. doi: 10.1007/s40200-023-01306-1. eCollection 2023 Dec.ABSTRACTPURPOSE: This registry aims to collect information to create an appropriate platform for the development of a basis for clinical research and basic sciences to carefully study pituitary adenomas.METHODS: Demographic data, diagnosis, treatment, and outcome information of the patients with a confirmed diagnosis of pituitary adenomas will be collected by investigators of the registry. Analysis of registry data generates aggregate reports summarizing pituitary tumor epidemiology, treatment, and outcome. These reports include annual public data reports. In the future, the registry program may provide a wider network in Iran and ultimately support the expansion of international studies.CONCLUSION: For a long time, patients with pituitary adenomas should be observed. Implementing a registration system would greatly reduce the challenges of patients' follow-up so that their monitoring can be improved.PMID:37975144 | PMC:PMC10638216 | DOI:10.1007/s40200-023-01306-1

J Diabetes Metab Disord. 2023 Sep 26;22(2):1657-1671. doi: 10.1007/s40200-023-01298-y. eCollection 2023 Dec.ABSTRACTPURPOSE: Chronic Kidney Disease (CKD) has become the 8th leading cause of death in Iran in 2017, 5 steps up from 1990. This is important as hypertension, diabetes, and chronic glomerulonephritis along with exposure to toxins or heavy metals are the main risk factors for the disease. Despite its heavy burden, there are limited studies on the incidence and prevalence of the disease in the Iranian adult population. The present article studies the burden of CKD at the national level in 2019, and its trend over the past three decades.METHODS: In 2019, the Global Burden of Disease (GBD) study provided an annual estimation of the burden of 369 diseases and injuries in 204 countries from 1990 until 2019. The data estimating CKD and related mortality in Iran were collected from the disease registry, survey, and scientific literature. All-ages and age-standardised indices of incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) were extracted for both sexes.RESULTS: Since 1990, the age-standardized incidence (34.7% (95% uncertainty interval 30.8 - 38.8)) and prevalence (19.6% (17.7 - 21.8)) of CKD have risen, while a 21.5% (-28.8 - -15.4) and 18.0% (-35.4 - -10.8) decrease were noted in age-standardized DALYs and deaths rates, respectively. The lowest prevalence was reported in the eastern and western provinces.CONCLUSION: Current study provides comprehensive knowledge about the CKD burden, suggesting the Iranian healthcare system has been more effective in averting deaths rather than managing morbidities. Multi-sectoral action plans are needed to strengthen preventive and early detection programs in high-risk areas.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01298-y.PMID:37975103 | PMC:PMC10638225 | DOI:10.1007/s40200-023-01298-y

J Diabetes Metab Disord. 2023 Jul 14;22(2):985-994. doi: 10.1007/s40200-023-01256-8. eCollection 2023 Dec.ABSTRACTOBJECTIVES: The exact underlying mechanism of developing diabetes-related cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is not clear. Metabolomics can provide a platform enabling the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The aim of this review is to summarize the available evidence on the relationship between metabolomics and cardiovascular diseases in patients with diabetes.METHODS: The literature was searched to find out studies that have investigated the relationship between the alteration of specific metabolites and cardiovascular diseases in patients with diabetes.RESULTS: Evidence proposed that changes in the metabolism of certain amino acids, lipids, and carbohydrates, independent of traditional CVD risk factors, are associated with increased CVD risk.CONCLUSIONS: Metabolomics can provide a platform to enable the prediction, diagnosis, and understanding of the risk of CVD in patients with diabetes mellitus. The association of the alteration in specific metabolites with CVD may be considered in the investigations for the development of new therapeutic targets for the prevention of CVD in patients with diabetes mellitus.PMID:37975080 | PMC:PMC10638133 | DOI:10.1007/s40200-023-01256-8

BMC Microbiol. 2023 Nov 16;23(1):343. doi: 10.1186/s12866-023-03085-4.ABSTRACTEndophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungi Aspergillus sp. SA1, Aspergillus sp. SA2, and Aspergillus sp. SA3, cultivated from Nigella sativa seeds against Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 13883), MRSA (ATCC 33591), and human pathogen Candida albicans (ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1-26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally, in-silico interactions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.PMID:37974074 | DOI:10.1186/s12866-023-03085-4

Nat Commun. 2023 Nov 16;14(1):7427. doi: 10.1038/s41467-023-43304-0.ABSTRACTAs one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomic analysis of lungs from JHU083-treated Mtb-infected mice reveals citrulline accumulation, suggesting elevated nitric oxide (NO) synthesis, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. JHU083-treated macrophages also produce more NO potentiating their antibacterial activity. When tested in an immunocompromised mouse model of Mtb infection, JHU083 loses its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.PMID:37973991 | DOI:10.1038/s41467-023-43304-0

Nat Metab. 2023 Nov 16. doi: 10.1038/s42255-023-00916-6. Online ahead of print.ABSTRACTTransient reprogramming by the expression of OCT4, SOX2, KLF4 and MYC (OSKM) is a therapeutic strategy for tissue regeneration and rejuvenation, but little is known about its metabolic requirements. Here we show that OSKM reprogramming in mice causes a global depletion of vitamin B12 and molecular hallmarks of methionine starvation. Supplementation with vitamin B12 increases the efficiency of reprogramming both in mice and in cultured cells, the latter indicating a cell-intrinsic effect. We show that the epigenetic mark H3K36me3, which prevents illegitimate initiation of transcription outside promoters (cryptic transcription), is sensitive to vitamin B12 levels, providing evidence for a link between B12 levels, H3K36 methylation, transcriptional fidelity and efficient reprogramming. Vitamin B12 supplementation also accelerates tissue repair in a model of ulcerative colitis. We conclude that vitamin B12, through its key role in one-carbon metabolism and epigenetic dynamics, improves the efficiency of in vivo reprogramming and tissue repair.PMID:37973897 | DOI:10.1038/s42255-023-00916-6