PubMed

iScience. 2023 Feb 25;26(3):106268. doi: 10.1016/j.isci.2023.106268. eCollection 2023 Mar 17.ABSTRACTPrevious prospective studies suggest that progression to autoimmune diseases is preceded by metabolic dysregulation, but it is not clear which metabolic changes are disease-specific and which are common across multiple immune-mediated diseases. Here we investigated metabolic profiles in cord serum in a general population cohort (All Babies In Southeast Sweden; ABIS), comprising infants who progressed to one or more immune-mediated diseases later in life: type 1 diabetes (n = 12), celiac disease (n = 28), juvenile idiopathic arthritis (n = 9), inflammatory bowel disease (n = 7), and hypothyroidism (n = 6); and matched controls (n = 270). We observed elevated levels of multiple triacylglycerols (TGs) an alteration in several gut microbiota related metabolites in the autoimmune groups. The most distinct differences were observed in those infants who later developed HT. The specific similarities observed in metabolic profiles across autoimmune diseases suggest that they share specific common metabolic phenotypes at birth that contrast with those of healthy controls.PMID:36915680 | PMC:PMC10005901 | DOI:10.1016/j.isci.2023.106268

Heliyon. 2023 Feb 16;9(3):e13821. doi: 10.1016/j.heliyon.2023.e13821. eCollection 2023 Mar.ABSTRACTOBJECTIVE: To compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles.METHODS: A multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16-35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named "Guanyuan" (CV4) and "Qihai" (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment.RESULTS: 76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC.CONCLUSION: LLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.PMID:36915513 | PMC:PMC10006448 | DOI:10.1016/j.heliyon.2023.e13821

Heliyon. 2023 Feb 24;9(3):e13985. doi: 10.1016/j.heliyon.2023.e13985. eCollection 2023 Mar.ABSTRACTBACKGROUND: NAFLD progression, from steatosis to inflammation and fibrosis, results from an interplay of intra- and extrahepatic mechanisms. Disease drivers likely include signals from white adipose tissue (WAT) and gut. However, the temporal dynamics of disease development remain poorly understood.METHODS: High-fat-diet (HFD)-fed Ldlr-/-.Leiden mice were compared to chow-fed controls. At t = 0, 8, 16, 28 and 38w mice were euthanized, and liver, WAT depots and gut were analyzed biochemically, histologically and by lipidomics and transcriptomics together with circulating factors to investigate the sequence of pathogenic events and organ cross-talk during NAFLD development.RESULTS: HFD-induced obesity was associated with an increase in visceral fat, plasma lipids and hyperinsulinemia at t = 8w, along with increased liver steatosis and circulating liver damage biomarkers. In parallel, upstream regulator analysis predicted that lipid catabolism regulators were deactivated and lipid synthesis regulators were activated. Subsequently, hepatocyte hypertrophy, oxidative stress and hepatic inflammation developed. Hepatic collagen accumulated from t = 16 w and became pronounced at t = 28-38 w. Epididymal WAT was maximally hypertrophic from t = 8 w, which coincided with inflammation development. Mesenteric and subcutaneous WAT hypertrophy developed slower and did not appear to reach a maximum, with minimal inflammation. In gut, HFD significantly increased permeability, induced a shift in microbiota composition from t = 8 w and changed circulating gut-derived metabolites.CONCLUSION: HFD-fed Ldlr-/-.Leiden mice develop obesity, dyslipidemia and insulin resistance, essentially as observed in obese NAFLD patients, underlining their translational value. We demonstrate that marked epididymal-WAT inflammation, and gut permeability and dysbiosis precede the development of NAFLD stressing the importance of a multiple-organ approach in the prevention and treatment of NAFLD.PMID:36915476 | PMC:PMC10006542 | DOI:10.1016/j.heliyon.2023.e13985

Comput Struct Biotechnol J. 2023 Feb 28;21:1785-1796. doi: 10.1016/j.csbj.2023.02.048. eCollection 2023.ABSTRACTZearalenone (ZEA), a secondary metabolite of Fusarium fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancer cells in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer-promoting effects of ZEA. This study aimed to determine the effect of ZEA on colon cancer progression and its underlying mechanisms. Through integrative analyses of transcriptomics, metabolomics, metagenomics, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed a twofold increase in tumor weight with the 4-week ZEA intervention. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB, and Ki67 and the phosphorylation levels of ERK1/2 and AKT. Serum metabolomic analysis revealed that the levels of amino acids, including histidine, arginine, citrulline, and glycine, decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the gut microbiota and reduced the abundance of nine genera, including Tuzzerella and Rikenella. Further association analysis indicated that Tuzzerella was negatively associated with the expression of BEST4 and DGKB genes, serum uric acid levels, and tumor weight. Additionally, circulatory hippuric acid levels positively correlated with tumor weight and the expression of oncogenic genes, including ROBO3, JAK3, and BEST4. Altogether, our results indicated that ZEA promotes colon cancer progression by enhancing the BEST4/AKT/ERK1/2 pathway, lowering circulatory amino acid concentrations, altering gut microbiota composition, and suppressing short chain fatty acids production.PMID:36915382 | PMC:PMC10006464 | DOI:10.1016/j.csbj.2023.02.048

Mikrochim Acta. 2023 Mar 13;190(4):132. doi: 10.1007/s00604-023-05712-3.ABSTRACTA combination of omics techniques (transcriptomics and metabolomics) has been used to elucidate the mechanisms responsible for the antitumor action of a nanosystem based on a Ag core coated with mesoporous silica on which transferrin has been anchored as a targeting ligand against tumor cells (Ag@MSNs-Tf). Transcriptomics analysis has been carried out by gene microarrays and RT-qPCR, while high-resolution mass spectrometry has been used for metabolomics. This multi-omics strategy has enabled the discovery of the effect of this nanosystem on different key molecular pathways including the glycolysis, the pentose phosphate pathway, the oxidative phosphorylation and the synthesis of fatty acids, among others.PMID:36914921 | DOI:10.1007/s00604-023-05712-3

Nat Metab. 2023 Mar 13. doi: 10.1038/s42255-023-00761-7. Online ahead of print.ABSTRACTOur understanding of how global changes in cellular metabolism contribute to human kidney disease remains incompletely understood. Here we show that nicotinamide adenine dinucleotide (NAD+) deficiency drives mitochondrial dysfunction causing inflammation and kidney disease development. Using unbiased global metabolomics in healthy and diseased human kidneys, we identify NAD+ deficiency as a disease signature. Furthermore using models of cisplatin- or ischaemia-reperfusion induced kidney injury in male mice we observed NAD+ depletion Supplemental nicotinamide riboside or nicotinamide mononucleotide restores NAD+ levels and improved kidney function. We find that cisplatin exposure causes cytosolic leakage of mitochondrial RNA (mtRNA) and activation of the cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I), both of which can be ameliorated by restoring NAD+. Male mice with RIG-I knock-out (KO) are protected from cisplatin-induced kidney disease. In summary, we demonstrate that the cytosolic release of mtRNA and RIG-I activation is an NAD+-sensitive mechanism contributing to kidney disease.PMID:36914909 | DOI:10.1038/s42255-023-00761-7

Sci Rep. 2023 Mar 13;13(1):4138. doi: 10.1038/s41598-023-31087-9.ABSTRACT2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that induces the progression of steatosis to steatohepatitis with fibrosis in mice. Furthermore, TCDD reprograms hepatic metabolism by redirecting glycolytic intermediates while inhibiting lipid metabolism. Here, we examined the effect of TCDD on hepatic acetyl-coenzyme A (acetyl-CoA) and β-hydroxybutyrate levels as well as protein acetylation and β-hydroxybutyrylation. Acetyl-CoA is not only a central metabolite in multiple anabolic and catabolic pathways, but also a substrate used for posttranslational modification of proteins and a surrogate indicator of cellular energy status. Targeted metabolomic analysis revealed a dose-dependent decrease in hepatic acetyl-CoA levels coincident with the phosphorylation of pyruvate dehydrogenase (E1), and the induction of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase phosphatase, while repressing ATP citrate lyase and short-chain acyl-CoA synthetase gene expression. In addition, TCDD dose-dependently reduced the levels of hepatic β-hydroxybutyrate and repressed ketone body biosynthesis gene expression. Moreover, levels of total hepatic protein acetylation and β-hydroxybutyrylation were reduced. AMPK phosphorylation was induced consistent with acetyl-CoA serving as a cellular energy status surrogate, yet subsequent targets associated with re-establishing energy homeostasis were not activated. Collectively, TCDD reduced hepatic acetyl-CoA and β-hydroxybutyrate levels eliciting starvation-like conditions despite normal levels of food intake.PMID:36914879 | DOI:10.1038/s41598-023-31087-9

Pediatr Res. 2023 Mar 13. doi: 10.1038/s41390-023-02538-w. Online ahead of print.ABSTRACTBACKGROUND: The objective of the study was to explore the potential biomarkers and risk factors in children with immunoglobulin A nephropathy (IgAN).METHODS: Untargeted metabolomics analysis was performed on children with IgAN before and after treatment. Subsequently, a retrospective study involving the past 15 years and a follow-up study were performed to verify the role of hyperuricemia in IgAN children.RESULTS: Serum metabolomics analyses showed that levels of serum xanthosine were closely related to the outcome of IgAN, and KEGG analyses showed that differential metabolites were significantly enriched in purine metabolism. Furthermore, retrospectively analyses of 252 children with IgAN showed that hyperuricemia was associated with poorer renal outcome. Logistic regression analysis showed that BMI, serum creatinine, eGFR, Lee's grade III, and crescents were risk factors of hyperuricemia in children with IgAN. Kaplan-Meier analysis revealed that kidney progression-free survival in IgAN children with hyperuricemia was lower than that without hyperuricemia, especially in females.CONCLUSIONS: We first performed a dynamic metabolomics study to reveal that hyperuricemia is closely related to the progression of IgAN in children. Then retrospective and follow-up studies confirmed that hyperuricemia is an important risk factor for poor renal outcomes. We need to pay more attention to the hyperuricemia in children with IgAN.IMPACT: We first performed a dynamic metabolomics study to reveal that hyperuricemia was closely related to the progression of IgAN in children. Retrospective analyses in past 15 years confirmed that IgAN children with hyperuricemia had poorer renal function and worse renal pathology. The BMI, Scr, eGFR, Lee's grade III, and crescents were risk factors of hyperuricemia in children with IgAN. The long-term follow-up study showed that hyperuricemia was an important risk factor for poor renal outcome in children with IgAN. We need to pay more attention to hyperuricemia in children with IgAN, especially in females.PMID:36914808 | DOI:10.1038/s41390-023-02538-w

Food Res Int. 2023 Apr;166:112489. doi: 10.1016/j.foodres.2023.112489. Epub 2023 Jan 20.ABSTRACTPurslane (Portulaca oleracea L.) has a high content of nutrients and medicinal effects that depend on the genotype, harvesting time, and production system. The objective of the present research work was to elucidate the NMR-based metabolomics profiling of three native purslane cultivars from Mexico (Xochimilco, Mixquic, and Cuautla) grown under hydroponic conditions and harvested in three different times (32, 39, and 46 days after emergence). Thirty-nine metabolites identified in the 1H NMR spectra of aerial parts of purslane, 5 sugars, 15 amino acids, 8 organic acids, 3 caffeoylquinic acids, as well as 2 alcohols and 3 nucleosides, choline, O-phosphocholine and trigonelline were also detected. A total of 37 compounds were detected in native purslane from Xochimilco and Cuautla, whereas 39 compounds were detected in purslane from Mixquic. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) separated the cultivars into three clusters. Mixquic cultivar had the highest number of differential compounds (amino acids and carbohydrates), followed by Xochimilco and Cuautla cultivars, respectively. Changes in the metabolome were observed in latest times of harvest for all the cultivars studied. The differential compounds were glucose, fructose, galactose, pyruvate, choline, and 2-hydroxysobutyrate. The results obtained in this investigation may contribute to selecting the best cultivar of purslane and the best time in which the levels of nutrients are optimal.PMID:36914359 | DOI:10.1016/j.foodres.2023.112489

Food Res Int. 2023 Apr;166:112591. doi: 10.1016/j.foodres.2023.112591. Epub 2023 Feb 16.ABSTRACTEpigallocatechin-3-gallate (EGCG), a flavoured and healthy compounds in tea, is affected by the ecological factors. However, the biosynthetic mechanisms of EGCG in response to the ecological factors remian unclear. In this study, a response surface method with a Box-Behnken design was used to investigate the relationship between EGCG accumulation and ecological factors; further, integrative transcriptome and metabolome analyses were performed to explore the mechanism underlying EGCG biosynthesis in response to environmental factors. The optimal environmental conditions obtained for EGCG biosynthesis were as follows: 28℃, 70 % relative humidity of the substrate, and 280 µmol·m-2·s-1 light intensity; the EGCG content was increased by 86.83 % compared to the control (CK1). Meanwhile, the order of EGCG content in response to the interaction of ecological factors was as follows: interaction of temperature and light intensity > interaction of temperature and relative humidity of the substrate > interaction of light intensity and relative humidity of the substrate, indicating that temperature was the dominant ecological factors. EGCG biosynthesis in tea plants was found to be comprehensively regulated by a series of structural genes (CsANS, CsF3H, CsCHI, CsCHS, and CsaroDE), miRNAs (miR164, miR396d, miR5264, miR166a, miR171d, miR529, miR396a, miR169, miR7814, miR3444b, and miR5240), and transcription factors (MYB93, NAC2, NAC6, NAC43, WRK24, bHLH30, and WRK70); further, the metabolic flux was regulated and converted from phenolic acid to the flavonoid biosynthesis pathway based on accelerated consumption of phosphoenolpyruvic acid, d-erythrose-4-phosphate, and l-phenylalanine in response to ambient changes in temperature and light intensity. Overall, the results of this study reveal the effect of ecological factors on EGCG biosynthesis in tea plants, providing novel insights for improving tea quality.PMID:36914346 | DOI:10.1016/j.foodres.2023.112591

Food Res Int. 2023 Apr;166:112603. doi: 10.1016/j.foodres.2023.112603. Epub 2023 Feb 17.ABSTRACTA range of volatile organic compounds played an important role in the formation of watermelon fruit aroma, while due to the low content and difficulty in detection, it is often neglected in watermelon breeding programs, resulting in a decline in fruit flavor. VOCs in the flesh of 194 watermelon accessions and seven cultivars at four developmental stages were determined by SPME-GC-MS. Ten metabolites with significant differences in the natural population and positive accumulation during fruit development are considered to be the key metabolite related to watermelon fruit aroma. And the link between metabolite and, flesh color and sugar content by correlation analysis was established. The results of the genome-wide association study showed that (5E)-6,10-dimethylundeca-5,9-dien-2-one, and 1-(4-methylphenyl) ethanone were colocalized with watermelon flesh color on chromosome 4, which may be regulated by LCYB and CCD. (E)-4-(2,6,6-trimethylcyclohexen-1-yl)but-3-en-2-one is the VOC produced by the cleavage of carotenoids, which has a positive correlation with the sugar content of the fruit, and the candidate gene Cla97C05G092490 on chromosome 5 may interact with PSY to influence the accumulation of this metabolite. In addition, Cla97C02G049790 (enol reductase), Cla97C03G051490 (omega-3 fatty acid desaturase gene), LOX, and ADH may play important roles in the synthesis of fatty acids and their derived VOCs. Taken together, our findings provide molecular insights into the accumulation and natural variation of VOCs in watermelon, and give data support for breeding watermelon cultivars with better flavor.PMID:36914327 | DOI:10.1016/j.foodres.2023.112603

Food Res Int. 2023 Apr;166:112587. doi: 10.1016/j.foodres.2023.112587. Epub 2023 Feb 9.ABSTRACTPlant growth-promoting rhizobacteria, such as Streptomyces pactum Act12, promote crop growth and stress resistance, but their contribution to fruit quality is still poorly understood. Herein we conducted a field experiment to ascertain the effects of S. pactum Act12-mediated metabolic reprogramming and underlying mechanisms in pepper (Capsicum annuum L.) fruit based on widely targeted metabolomic and transcriptomic profiling. We additionally performed metagenomic analysis to elucidate the potential relationship between S. pactum Act12-mediated reshaping of rhizosphere microbial communities and pepper fruit quality. Soil inoculation with S. pactum Act12 considerably increased the accumulation of capsaicinoids, carbohydrates, organic acids, flavonoids, anthraquinones, unsaturated fatty acids, vitamins, and phenolic acids in pepper fruit samples. Consequently, fruit flavor, taste, and color were modified, accompanied by elevated contents of nutrients and bioactive compounds. Increased microbial diversity and recruitment of potentially beneficial taxa were observed in inoculated soil samples, with crosstalk between microbial gene functions and pepper fruit metabolism. The reformed structure and function of rhizosphere microbial communities were closely associated with pepper fruit quality. Our findings indicate that S. pactum Act12-mediated interactions between rhizosphere microbial communities and pepper plants are responsible for intricate fruit metabolic reprogramming patterns, which enhance not only overall fruit quality but also consumer acceptability.PMID:36914318 | DOI:10.1016/j.foodres.2023.112587

Food Res Int. 2023 Apr;166:112585. doi: 10.1016/j.foodres.2023.112585. Epub 2023 Feb 9.ABSTRACTThe fermentation process of traditional shrimp paste is closely associated with the production of flavor substances, but the formation mechanism of key aroma components is still unclear. In this study, a comprehensively flavor profile analysis of traditional fermented shrimp paste was carried out by E-nose and SPME-GC-MS. A total of 17 key volatile aroma components with OAV > 1 contributed greatly to the overall flavor formation of shrimp paste. In addition, high-throughput sequencing (HTS) analysis revealed that Tetragenococcus was the dominant genera in the whole fermentation process. Moreover, metabolomics analysis showed that the oxidation and degradation of lipids, protein, organic acids and amino acids produced a large number of flavor substances and intermediates, which laid the foundation for the Maillard reaction in term of generating the distinct aroma of the traditional shrimp paste. This work will provide theoretical support for the realization of flavor regulation and quality control in traditional fermented foods.PMID:36914317 | DOI:10.1016/j.foodres.2023.112585

Food Res Int. 2023 Apr;166:112584. doi: 10.1016/j.foodres.2023.112584. Epub 2023 Feb 9.ABSTRACTAllium is one of the most extensively consumed spices in most parts of the world. While Allium cepa and A. sativum have wide spread cultivation, A. semenovii is only found in high altitude areas. Increasing utilization of A. semenovii needs a comprehensive understanding of its chemo-information, and health benefits in comparison to well explored Allium species. The present study compared metabolome and antioxidant activity in tissues extracts (Ethanol, 50% ethanol and water) of leaves, roots, bulbs, and peels of the three Allium species. All samples showed significant polyphenols (TPC: 167.58-0.22 mg GAE/g and TFC: 164.86-2.2 mg QE/g) content with higher antioxidant activity in A. cepa and A. semenovii than A. sativum. UPLC-PDA based targeted polyphenol also showed highest content in A. cepa (peels, roots, and bulbs) and A. semenovii (leaves). Further, 43 diversified metabolites including polyphenols and sulphur containing compounds were identified using GC-MS and UHPLC-QTOF-MS/MS. The statistical analysis (Venn-diagram, Heatmap, stacked charts, PCA, PCoA) of identified metabolites in different samples revealed the similarities and discriminations among different species of Allium. The current finding illustrated potential of A. semenovii for utilisation in food and nutraceuticals.PMID:36914316 | DOI:10.1016/j.foodres.2023.112584

Food Res Int. 2023 Apr;166:112550. doi: 10.1016/j.foodres.2023.112550. Epub 2023 Feb 2.ABSTRACTIntramuscular fat (IMF) content, which is an important determinant of meat quality characteristics such as tenderness, juiciness and flavor, has long been a research hotspot. Chinese local pig breeds are famous for their excellent meat quality which is mainly reflected in the high IMF content, strong hydraulic system and et al. However, there are few analysis of meat quality by omics methods. In our study, we identified 12 different fatty acids, 6 different amino acids, 1,262 differentially expression genes (DEGs), 140 differentially abundant proteins (DAPs) and 169 differentially accumulated metabolites (DAMs) (p < 0.05) with metabolome, transcriptome, and proteome. It has been found that DEGs, DAPs and DAMs were enriched in the Wnt signaling pathway, PI3K-Akt signaling pathway, Rap1 signaling pathway, and Ras signaling pathway which were related to meat quality. Moreover, our Weighted genes co-expression network construction (WGCNA) showed RapGEF1 was the key gene related to IMF content and the RT-qPCR analysis was used to perform validation of the significant genes. In summary, our study provided both fundamental data and new insights to further uncover the secret of pig IMF content.PMID:36914311 | DOI:10.1016/j.foodres.2023.112550

Food Res Int. 2023 Apr;166:112546. doi: 10.1016/j.foodres.2023.112546. Epub 2023 Feb 1.ABSTRACTPatulin (PAT), a toxin produced by molds in fruits and related products, has caused frequent food poisoning incidents worldwide. However, its potential mechanism of hepatotoxicity remains presently unclear. Herein, we intragastrically administered the C57BL/6J mice with 0, 1, 4, and 16 mg/kg b.wt of PAT on a single occasion (acute model), and 0, 50, 200, and 800 μg/kg b.wt of PAT daily over two weeks (subacute model). Assessments of histopathology and aminotransferase activities confirmed that significant hepatic damages were induced. Metabolic profiling on the liver using ultra-high-performance liquid chromatography high-resolution mass spectrometry discovered 43 and 61 differential metabolites in two models, respectively. Notably, acute and subacute models shared the common 18 differential metabolites, among which N-acetyl-leucine, inosine, 2-O-methyladenosine, PC 40:7, PC 38:6, and PC 34:2 could be regarded as the biomarkers indicative of PAT exposure. Moreover, analysis of metabolic pathways demonstrated that pentose phosphate pathway and purine metabolism were the main altered pathways in the acute model. Nevertheless, more pathways related to amino acids were affected in the subacute model. These results reveal the comprehensive influence of PAT on hepatic metabolism and provide a deeper understanding of the hepatotoxicity mechanism of PAT.PMID:36914310 | DOI:10.1016/j.foodres.2023.112546

BMJ Open. 2023 Mar 13;13(3):e058847. doi: 10.1136/bmjopen-2021-058847.ABSTRACTINTRODUCTION: Ramadan fasting is globally observed and a great majority of the residents of Islamic countries and elsewhere fast during Ramadan all across the world every year. Many patients with type 1 diabetes fast during Ramadan according to (or against) medical and jurisprudence advice. Nonetheless, there is a paucity of scientific evidence regarding the risks patients with diabetes who fast may be confronted with. The current scoping review protocol aims at systematic analysis and mapping of existing literature in the field and highlighting scientific gaps.METHODS AND ANALYSES: This scoping review will be conducted based on the Arksey and O'Malley's methodological framework with consideration of later modifications and amendments. Three major scientific databases, namely PubMed, Scopus and Embase up to February 2022 will be systematically searched by expert researchers in collaboration with a medical librarian. Considering the fact that Ramadan Fasting is a cultural-dependent subject, which may be studied in the Middle Eastern and Islamic Countries in languages other than English, local Persian and Arabic Databases will also be included. Grey literature will be sought too, and unpublished works such as conference proceedings and academic degree dissertation will be considered. Subsequently, one author will screen and record all abstracts, and two reviewers will independently screen and retrieve eligible full texts. A third reviewer will then be designated to resolve potential discrepancies. Standardised data charts and forms will be used for information extraction and reporting of the outcomes.ETHICS AND DISSEMINATION: No ethical considerations apply to this research. Results will be published and presented in academic journals and scientific events.PMID:36914196 | DOI:10.1136/bmjopen-2021-058847

Planta Med. 2023 Mar 13. doi: 10.1055/a-2053-0950. Online ahead of print.ABSTRACTDiabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aimed to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC has been tested on a streptozotocin-nicotinamide (STZ-NA) induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses revealed that treatment with 250 mg/kg body weight (bw) standardized freeze dried (FD) 50% ethanolic MC extract (MCE 250) showed favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicated the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate were identified in rats' urinary profile discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA was due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA induced diabetic rats showed improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.PMID:36914160 | DOI:10.1055/a-2053-0950

Sci Total Environ. 2023 Mar 11:162818. doi: 10.1016/j.scitotenv.2023.162818. Online ahead of print.ABSTRACTFreshwater ecosystems are characterised by the co-occurrence of stressors that simultaneously affect the biota. Among these, flow intermittency and chemical pollution severely impair the diversity and functioning of streambed bacterial communities. Using an artificial streams mesocosm facility, this study examined how desiccation and pollution caused by emerging contaminants affect the composition of stream biofilm bacterial communities, their metabolic profiles, and interactions with their environment. Through integrative analysis of the composition of biofilm communities, characterization of their metabolome and composition of the dissolved organic matter, we found strong genotype-to-phenotype interconnections. The strongest correlation was found between the composition and metabolism of the bacterial community, both of which were influenced by incubation time and desiccation. Unexpectedly, no effect of the emerging contaminants was observed, which was due to the low concentration of the emerging contaminants and the dominant impact of desiccation. However, biofilm bacterial communities modified the chemical composition of their environment under the effect of pollution. Considering the tentatively identified classes of metabolites, we hypothesised that the biofilm response to desiccation was mainly intracellular while the response to chemical pollution was extracellular. The present study demonstrates that metabolite and dissolved organic matter profiling may be effectively integrated with compositional analysis of stream biofilm communities to yield a more complete picture of changes in response to stressors.PMID:36914121 | DOI:10.1016/j.scitotenv.2023.162818

J Ethnopharmacol. 2023 Mar 11:116367. doi: 10.1016/j.jep.2023.116367. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort., Apiaceae, Chuanxiong in Chinese) both are important traditional Chinese medicine (TCM) for activating blood and eliminating stasis. Danshen-chuanxiong herb pair has been used for more than 600 years in China. Guanxinning injection (GXN) is a Chinese clinical prescription refined from aqueous extract of Danshen and Chuanxiong at the ratio of 1:1 (w/w). GXN has been mainly used in the clinical therapy of angina, heart failure (HF) and chronic kidney disease in China for almost twenty years.AIM OF THE STUDY: This study aimed to explore the role of GXN on renal dysfunction and fibrosis in heart failure mice and the regulation of GXN on SLC7A11/GPX4 axis.MATARIALS AND METHODS: The transverse aortic constriction model was used to mimic HF accompanied by kidney fibrosis model. GXN was administrated by tail vein injection in dose of 12.0, 6.0, 3.0 mL/kg, respectively. Telmisartan (6.1 mg/kg, gavage) was used as a positive control drug. Cardiac ultrasound indexes of ejection fraction (EF), cardiac output (CO), left ventricle volume (LV Vol), HF biomarker of pro-B type natriuretic peptide (Pro-BNP), kidney function index of serum creatinine (Scr), kidney fibrosis index of collagen volume fraction (CVF) and Connective tissue growth factor (CTGF) were evalauted and contrasted. Metabolomic method was employed to analyze the endogenous metabolites changes in kidneys. Besides, contents of catalase (CAT), xanthine oxidase (XOD), nitricoxidesynthase (NOS), glutathione peroxidase 4 (GPX4), the x(c)(-) cysteine/glutamate antiporter consists of a light chain subunit (SLC7A11) and ferritin Heavy Chain (FTH1) in kidney were quantitatively analyzed. In addition, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical composition of GXN and network pharmacology was used to predict possible mechanisms and the active ingredients of GXN.RESULTS: The cardiac function indexes of EF, CO and LV Vol, kidney functional indicators of Scr, the degree of kidney fibrosis indicators CVF and CTGF were all relieved to different extent for the model mice treated with GXN. 21 differential metabolites involved in redox regulation, energy metabolism, organic acid metabolism, nucleotide metabolism, etc were identified. Aspartic acid, homocysteine, glycine, and serine, methionine, purine, phenylalanine and tyrosine metabolism were found to be the core redox metabolic pathways regulated by GXN. Furthermore, GXN were found to increase CAT content, upregulate GPX4, SLC7A11 and FTH1 expression in kidney significantly. Not only that, GXN also showed good effect in down-regulating XOD and NOS contents in kidney. Besides, 35 chemical constituents were initially identified in GXN. Active ingredients of GXN-targets-related enzymes/transporters-metabolites network was estiblished to find out that GPX4 was a core protein involved for GXN and the top 10 active ingredients with the most relevant to renal protective effects of GXN were rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A.CONCLUSION: GXN could significantly maintain cardiac function and alleviate the progression of fibrosis in the kidney for heart failure mice, and the mechanisms of action were related to regulating redox metabolism of aspartate, glycine, serine, and cystine metabolism and SLC7A11/GPX4 axis in kidney. The cardio-renal protective effect of GXN may be attributed to multi-components like rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A et al.PMID:36914037 | DOI:10.1016/j.jep.2023.116367