PubMed

Adv Sci (Weinh). 2022 Nov 23:e2205645. doi: 10.1002/advs.202205645. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen-induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC-MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ-glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production.PMID:36417588 | DOI:10.1002/advs.202205645

Adv Biol (Weinh). 2022 Nov 23:e2200233. doi: 10.1002/adbi.202200233. Online ahead of print.ABSTRACTRelapses negatively impact cancer patient survival due to the tumorigenesis ability of surviving cancer cells post-therapy. Efforts are needed to better understand and combat this problem. This study hypothesized that dead cell debris post-radiation therapy creates an advantageous microenvironment rich in metabolic materials promoting the growth of remaining live cancer cells. In this study, live cancer cells are co-cultured with dead cancer cells eradicated by UV radiation to mimic a post-therapy environment. Isotopic labeling metabolomics is used to investigate the metabolic behavior of cancer cells grown in a post-radiation-therapy environment. It is found that post-UV-eradicated dead cancer cells serve as nutritional sources of "off-the-shelf" and precursor metabolites for surviving cancer cells. The surviving cancer cells then take up these metabolites, integrate and upregulate multiple vital metabolic processes, thereby significantly increasing growth in vitro and probably in vivo beyond their intrinsic fast-growing characteristics. Importantly, this active metabolite uptake behavior is only observed in oncogenic but not in non-oncogenic cells, presenting opportunities for therapeutic approaches to interrupt the active uptake process of oncogenic cells without affecting normal cells. The process by which living cancer cells re-use vital metabolites released by dead cancer cells post-therapy is coined in this study as "metabolic recycling" of oncogenic cells.PMID:36417583 | DOI:10.1002/adbi.202200233

Chem Biodivers. 2022 Nov 23. doi: 10.1002/cbdv.202200667. Online ahead of print.ABSTRACT<p class="CB-Dedication" style="margin: 6pt 0cm; text-align: justify; line-height: 16px; font-size: 8pt; font-family: &quot;Myriad Pro&quot;, sans-serif; caret-color: rgb(0, 0, 0); color: rgb(0, 0, 0);"><span lang="EN-US">The leaves of&nbsp;<italic>Piper auritum</italic>&nbsp;Kunth (&ldquo;Hoja Santa&rdquo;) have been consumed for centuries by native people of central and southern Mexico as a fresh vegetable or condiment. Herein we present the result of the&nbsp;1H NMR metabolomics profiling of three accessions of&nbsp;<italic>P. auritum</italic>&nbsp;harvested in three different provinces of Mexico (Puebla, Tlaxcala, and Oaxaca). The volatile content associated with the flavoring properties of the plant was also determined by GC-MS. The non-targeted metabolome of these samples revealed that&nbsp;<italic>P. auritum</italic>&nbsp;is a source of&nbsp;</span><span lang="EN-US" style="line-height: 16px;">free essential amino acids such as isoleucine, leucine, threonine, valine, histidine, phenylalanine, and tryptophan as well as organic acids, free monosaccharides, and valuable nutraceuticals such as trigonelline, myo-inositol, betaine, and choline. Principal component analysis and orthogonal partial least squares discriminated analysis of the metabolites found in&nbsp;<italic>P. auritum</italic>&nbsp;and revealed trigonelline as the main differential compound found in the three studied accessions, suggesting this metabolite as a possible chemical marker. According to these statistical approaches, 60% of the differential metabolites were provided by Oaxaca samples, suggesting that leaves collected there have better (p &lt; 0.05) nutritional properties than the other samples analyzed. Nevertheless, the high abundance of the anti-nutrient safrole (90%) in the volatile fraction, advises of potential toxicity of&nbsp;<italic>P. auritum&nbsp;</italic>consumed in Oaxaca. On the other hand, samples harvested in the northern highlands of Puebla, contained the lowest levels of safrole (30%) and acceptable levels of nutrients and nutraceuticals including choline. From the three groups of studied plants, those harvested in the northern highlands from Puebla, could be considered safer for human consumption than the other analyzed accessions.&nbsp;</span><span lang="EN-US"><o:p></o:p></span></p>.PMID:36417317 | DOI:10.1002/cbdv.202200667

Plant Physiol. 2022 Nov 23:kiac519. doi: 10.1093/plphys/kiac519. Online ahead of print.ABSTRACTNitrogen is critical for plant growth and development. With the increase of nitrogen fertilizer application, nitrogen use efficiency decreases, resulting in wasted resources. In apple (Malus domestica) rootstocks, the potential molecular mechanism for improving nitrogen uptake efficiency to alleviate low nitrogen stress remains unclear. We utilized multi-omics approaches to investigate the mechanism of nitrogen uptake in two apple rootstocks with different responses to nitrogen stress, Malus hupehensis and Malus sieversii. Under low nitrogen stress, Malus sieversii showed higher efficiency in nitrogen uptake. Multi-omics analysis revealed substantial differences in the expression of genes involved in flavonoid and lignin synthesis pathway between the two materials, which were related to the corresponding metabolites. We discovered that basic helix-loop-helix 130 (bHLH130) transcription factor was highly negatively associated with the flavonoid biosynthetic pathway. bHLH130 may directly bind to the chalcone synthase gene (CHS) promoter and inhibit its expression. Overexpressing CHS increased flavonoid accumulation and nitrogen uptake. Inhibiting bHLH130 increased flavonoid biosynthesis while decreasing lignin accumulation, thus improving nitrogen uptake efficiency. These findings revealed the molecular mechanism by which bHLH130 regulates flavonoid and lignin biosynthesis in apple rootstocks under low nitrogen stress.PMID:36417197 | DOI:10.1093/plphys/kiac519

Gut Microbes. 2022 Jan-Dec;14(1):2149019. doi: 10.1080/19490976.2022.2149019.ABSTRACTThe bacteria-derived short-chain fatty acids (SCFAs) butyrate and propionate play important (distinct) roles in health and disease, and understanding the ecology of respective bacteria on a community-wide level is a top priority in microbiome research. Applying sequence data (metagenomics and 16S rRNA gene) to predict SCFAs production in vitro and in vivo, a clear split between butyrate- and propionate-forming bacteria was detected with only very few taxa exhibiting pathways for the production of both SCFAs. After in vitro growth of fecal communities from distinct donors (n = 8) on different substrates (n = 7), abundances of bacteria exhibiting pathways correlated with respective SCFA concentrations, in particular in the case of butyrate. For propionate, correlations were weaker, indicating that its production is less imprinted into the core metabolism compared with butyrate-forming bacteria. Longitudinal measurements in vivo (n = 5 time-points from 20 subjects) also revealed a correlation between abundances of pathway-carrying bacteria and concentrations of the two SCFAs. Additionally, lower bacterial cell concentrations, together with higher stool moisture, promoted overall bacterial activity (measured by flow cytometry and coverage patterns of metagenome-assembled genomes) that led to elevated SCFA concentrations with over-proportional levels of butyrate. Predictions on pathway abundances based on 16S rRNA gene data using our in-house database worked well, yielding similar results as metagenomic-based analyses. Our study indicates that stimulating growth of butyrate- and propionate-producing bacteria directly leads to more production of those compounds, which is governed by two functionally distinct bacterial groups facilitating the development of precision intervention strategies targeting either metabolite.PMID:36416760 | DOI:10.1080/19490976.2022.2149019

mSphere. 2022 Nov 23:e0018422. doi: 10.1128/msphere.00184-22. Online ahead of print.ABSTRACTPlasmid-mediated antimicrobial resistance is one of the major threats to public health worldwide. The mechanisms involved in the plasmid/host coadaptation are still poorly characterized, and their understanding is crucial to comprehend the genesis and evolution of multidrug-resistant bacteria. With this purpose, we designed an experimental evolution using Haemophilus influenzae RdKW20 as the model strain carrying the ColE1-like plasmid pB1000. Five H. influenzae populations adapted previously to the culture conditions were transformed with pB1000 and subsequently evolved to compensate for the plasmid-associated fitness cost. Afterward, we performed an integrative multiomic analysis combining genomics, transcriptomics, and metabolomics to explore the molecular mechanisms involved in the compensatory evolution of the plasmid. Our results demonstrate that minimal modifications in the host are responsible for plasmid adaptation. Among all of them, the most enriched process was amino acid metabolism, especially those pathways related to serine, tryptophan, and arginine, eventually related to the genesis and resolution of plasmid dimers. Additional rearrangements occurred during the plasmid adaptation, such as an overexpression of the ribonucleotide reductases and metabolic modifications within specific membrane phospholipids. All these findings demonstrate that the plasmid compensation occurs through the combination of diverse host-mediated mechanisms, of which some are beyond genomic and transcriptomic modifications. IMPORTANCE The ability of bacteria to horizontally transfer genetic material has turned antimicrobial resistance into one of the major sanitary crises of the 21st century. Plasmid conjugation is considered the main mechanism responsible for the mobilization of resistance genes, and its understanding is crucial to tackle this crisis. It is generally accepted that the acquisition and maintenance of mobile genetic elements entail a fitness cost to its host, which is susceptible to be alleviated through a coadaptation process or compensatory evolution. Notwithstanding, despite recent major efforts, the underlying mechanisms involved in this adaptation remain poorly characterized. Analyzing the plasmid/host coadaptation from a multiomic perspective sheds light on the physiological processes involved in the compensation, providing a new understanding on the genesis and evolution of plasmid-mediated antimicrobial-resistant bacteria.PMID:36416553 | DOI:10.1128/msphere.00184-22

mSystems. 2022 Nov 23:e0071022. doi: 10.1128/msystems.00710-22. Online ahead of print.ABSTRACTThe metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas-the birthplace and the last continental expansion of our species, respectively-we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features such as amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, coanalyses with over 5,000 publicly available human fecal samples and cooccurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient. IMPORTANCE As the world becomes increasingly industrialized, understanding the biological consequences of these lifestyle shifts and what it means for past, present, and future human health is critical. Indeed, industrialization is associated with rises in allergic and autoimmune health conditions and reduced microbial diversity. Exploring these health effects on a chemical level requires consideration of human lifestyle diversity, but understanding the significance of any differences also requires knowledge of what molecular components are shared between human groups. Our study reveals the key chemistry of the human gut as defined by varied industrialization-based differences and ubiquitous shared features. Ultimately, these novel findings extend our knowledge of human molecular biology, especially as it is influenced by lifestyle and behavior, and provide steps toward understanding how human biology has changed over our species' history.PMID:36416540 | DOI:10.1128/msystems.00710-22

Int J Epidemiol. 2022 Nov 23:dyac218. doi: 10.1093/ije/dyac218. Online ahead of print.NO ABSTRACTPMID:36416418 | DOI:10.1093/ije/dyac218

Electrophoresis. 2022 Nov 23. doi: 10.1002/elps.202200257. Online ahead of print.ABSTRACTThe goal of integrative top-down proteomics (i.e., two-dimensional gel electrophoresis (2DE) coupled with liquid chromatography and tandem mass spectrometry (LC/MS/MS)) is a routine analytical approach that fully addresses the breadth and depth of proteomes. To accomplish this, there should be no addition, removal, or modification to any constituent proteoforms. To address two-decade old claims of protein losses during front-end proteome resolution using 2DE, here we tested an alternate rehydration method for immobilized pH gradient strips prior to isoelectric focusing (IEF; i.e., face-up compared to face-down) and quantitatively assessed losses during the front-end of 2DE (rehydration and IEF). Using a well-established high-resolution, quantitative 2DE protocol, there were no detectable proteoform losses using the alternate face-up rehydration method. While there is a <0.25% total loss of proteoforms during standard face-down rehydration, it is insignificant in terms of having any effect on overall proteome resolution (i.e., total spot count and total spot signal). This report is another milestone in integrative top-down proteomics, disproving long-held dogma in the field and confirming that quantitative front-end 2DE/LC/MS/MS is currently the only method to broadly and deeply analyze proteomes by resolving their constituent proteoforms. This article is protected by copyright. All rights reserved.PMID:36416355 | DOI:10.1002/elps.202200257

Brief Bioinform. 2022 Nov 22:bbac485. doi: 10.1093/bib/bbac485. Online ahead of print.ABSTRACTMedicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas.PMID:36416120 | DOI:10.1093/bib/bbac485

FASEB J. 2022 Dec;36(12):e22644. doi: 10.1096/fj.202201473R.ABSTRACTMaternal obesity (MO) during pregnancy is linked to increased and premature risk of age-related metabolic diseases in the offspring. However, the underlying molecular mechanisms still remain not fully understood. Using a well-established nonhuman primate model of MO, we analyzed tissue biopsies and plasma samples obtained from post-pubertal offspring (3-6.5 y) of MO mothers (n = 19) and from control animals born to mothers fed a standard diet (CON, n = 13). All offspring ate a healthy chow diet after weaning. Using untargeted gas chromatography-mass spectrometry metabolomics analysis, we quantified a total of 351 liver, 316 skeletal muscle, and 423 plasma metabolites. We identified 58 metabolites significantly altered in the liver and 46 in the skeletal muscle of MO offspring, with 8 metabolites shared between both tissues. Several metabolites were changed in opposite directions in males and females in both liver and skeletal muscle. Several tissue-specific and 4 shared metabolic pathways were identified from these dysregulated metabolites. Interestingly, none of the tissue-specific metabolic changes were reflected in plasma. Overall, our study describes characteristic metabolic perturbations in the liver and skeletal muscle in MO offspring, indicating that metabolic programming in utero persists postnatally, and revealing potential novel mechanisms that may contribute to age-related metabolic diseases later in life.PMID:36415994 | DOI:10.1096/fj.202201473R

Gates Open Res. 2022 Jul 18;6:77. doi: 10.12688/gatesopenres.13635.1. eCollection 2022.ABSTRACTIntroduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.PMID:36415883 | PMC:PMC9646488 | DOI:10.12688/gatesopenres.13635.1

Endocrinol Diabetes Metab. 2022 Nov 22. doi: 10.1002/edm2.388. Online ahead of print.ABSTRACTOBJECTIVES: Insulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program.METHODS: Fasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA-IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables.RESULTS: Baseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI-metrics. Following lifestyle-intervention, α-keto-β-methylvalerate (α-KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA-IR at 6-month-follow-up. Glutamate/glutamine was positively associated with HOMA-IR at baseline and 6-month-follow-up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6-month-follow-up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight.CONCLUSIONS: BCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle-intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.PMID:36415168 | DOI:10.1002/edm2.388

J Anim Physiol Anim Nutr (Berl). 2022 Nov 22. doi: 10.1111/jpn.13790. Online ahead of print.ABSTRACTThis study explored the mechanism by which grape seed procyanidins (GSPs) alleviate colon inflammatory injury induced by a high-concentrate diet in lambs. Forty-eight 1/2 Dorper (♂) × 1/2 Small thin-tailed (♀) crossed male lambs were randomly assigned into four groups: the control group (CON), fed with a high-concentrate diet (concentrate:forage = 7:3) and three GSPs groups fed a high-concentrate diet + 10 (LGSP), 20 (MGSP) and 40 (HGSP) mg/kg body weight (BW) GSPs per day, respectively. The results showed that the levels of interleukin (IL)-1β and tumour necrosis factor (TNF)-α in plasma of lambs of the MGSP (0.155 and 38.52 pg/ml) and HGSP (0.165 and 39.60 pg/ml) groups were significantly lower than those in the CON (0.248 and 48.74 pg/ml) and LGSP (0.245 and 50.52 pg/ml) group (p < 0.05), and levels of IL-1β in colon tissue in the MGSP (28.49 ng/g) and HGSP (26.67 ng/g) groups were also lower (p < 0.05) than that in CON (40.55 ng/g). Metabonomics analysis of colon tissue showed that differentially expressed metabolites were mainly enriched in the arachidonic acid metabolism, citric acid cycle, glycine, serine and threonine metabolism, and peroxisome proliferator-activated receptor signalling pathway (p < 0.05). In conclusion, GSPs alleviate the colonic epithelium inflammatory response induced by a high-concentrate diet by increasing energy metabolism, amino acid metabolism, antioxidant metabolism and inhibiting arachidonic acid metabolism.PMID:36415155 | DOI:10.1111/jpn.13790

Quant Plant Biol. 2022 Nov 22;3:e26. doi: 10.1017/qpb.2022.19. eCollection 2022.ABSTRACTMobilisation of seed storage reserves is important for seedling establishment in Arabidopsis. In this process, sucrose is synthesised from triacylglycerol via core metabolic processes. Mutants with defects in triacylglycerol-to-sucrose conversion display short etiolated seedlings. We found that whereas sucrose content in the indole-3-butyric acid response 10 (ibr10) mutant was significantly reduced, hypocotyl elongation in the dark was unaffected, questioning the role of IBR10 in this process. To dissect the metabolic complexity behind cell elongation, a quantitative-based phenotypic analysis combined with a multi-platform metabolomics approach was applied. We revealed that triacylglycerol and diacylglycerol breakdown were disrupted in ibr10, resulting in low sugar content and poor photosynthetic ability. Importantly, batch-learning self-organised map clustering revealed that threonine level was correlated with hypocotyl length. Consistently, exogenous threonine supply stimulated hypocotyl elongation, indicating that sucrose levels are not always correlated with etiolated seedling length, suggesting the contribution of amino acids in this process.PMID:37077988 | PMC:PMC10095960 | DOI:10.1017/qpb.2022.19

BMC Med. 2022 Nov 21;20(1):450. doi: 10.1186/s12916-022-02653-1.ABSTRACTBACKGROUND: Glucose metabolism has been reported to be affected by dietary patterns, while the underlying mechanisms involved remain unclear. This study aimed to investigate the potential mediation role of circulating metabolites in relation to dietary patterns for prediabetes and type 2 diabetes.METHODS: Data was derived from The Maastricht Study that comprised of 3441 participants (mean age of 60 years) with 28% type 2 diabetes patients by design. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ), and the glucose metabolism status (GMS) was defined according to WHO guidelines. Both cross-sectional and prospective analyses were performed for the circulating metabolome to investigate their associations and mediations with responses to dietary patterns and GMS.RESULTS: Among 226 eligible metabolite measures obtained from targeted metabolomics, 14 were identified to be associated and mediated with three dietary patterns (i.e. Mediterranean Diet (MED), Dietary Approaches to Stop Hypertension Diet (DASH), and Dutch Healthy Diet (DHD)) and overall GMS. Of these, the mediation effects of 5 metabolite measures were consistent for all three dietary patterns and GMS. Based on a 7-year follow-up, a decreased risk for apolipoprotein A1 (APOA1) and docosahexaenoic acid (DHA) (RR 0.60, 95% CI 0.55, 0.65; RR 0.89, 95% CI 0.83, 0.97, respectively) but an increased risk for ratio of ω-6 to ω-3 fatty acids (RR 1.29, 95% CI 1.05, 1.43) of type 2 diabetes were observed from prediabetes, while APOA1 showed a decreased risk of type 2 diabetes from normal glucose metabolism (NGM; RR 0.82, 95% CI 0.75, 0.89).CONCLUSIONS: In summary, this study suggests that adherence to a healthy dietary pattern (i.e. MED, DASH, or DHD) could affect the GMS through circulating metabolites, which provides novel insights into understanding the biological mechanisms of diet on glucose metabolism and leads to facilitating prevention strategy for type 2 diabetes.PMID:36414942 | DOI:10.1186/s12916-022-02653-1

J Ethnopharmacol. 2022 Nov 19:115943. doi: 10.1016/j.jep.2022.115943. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: As one of the most commonly used herbs, Artemisia capillaris Thunb. (ACT) display favorable effect in the treatment of jaundice. However, mechanism of ACT in the treatment of jaundice remains unclear at present, which limits its development and application.AIM OF THE STUDY: To investigate effect and mechanism of Artemisia capillaris Thunb. (ACT) in the treatment of jaundice using pharmacodynamics, network pharmacology and metabolomics.METHODS: Effect of ACT in treating jaundice was evaluated by biochemical assays and pathological observation using the α-naphthyl isothiocyanate (ANIT)-induced mice. Jaundice-relieving mechanism of ACT was investigated by integration of network pharmacology and metabolomics.RESULTS: After the mice with jaundice were administrated ACT extract for 9 days, compared to that of the model group, serum D-BIL, T-BIL and ALP levels of the mice in the low, medium, high dose of ACT group decreased by 39.81%, 15.30% and 16.92%; 48.06%, 42.54% and 36.91%; 26.90%, 12.34% and 16.90%, respectively. The pathologic study indicated that ACT improved the symptoms of liver injury of the mice with jaundice. The network of herb (i.e., ACT)-components-targets-disease (i.e., jaundice) was established, which consisted of 17 components classified in flavonoids, chromones, organic acids, terpenoids, and 234 targets related to treatment of jaundice. Metabolomics analysis showed that, compared to that in the model group, level of 8 differential metabolites were upregulated and level of 29 differential metabolites were downregulated in the mice liver in the ACT group, respectively. The main metabolic pathways involved in treatment of jaundice by ACT were pantothenate and CoA biosynthesis, glutathione metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis in the liver, respectively. The integrated analysis of network pharmacology and metabolomics showed that 3α,7α,12α a-Trihydroxy-5β-cholanate, glycocholate, taurocholate, pantetheine 4'-phosphate, and d-4'-phosphopantothenate were the potential biomarkers for treatment of jaundice, and AKR1C4, ALDH2 and HSD11B were the potential drug targets in the treatment of jaundice by ACT.CONCLUSION: The study based on metabolomics and network pharmacology indicated that ACT can display favorable jaundice-relieving effect by its multiple components regulating multiple biomarkers, multiple targets and multiple pathways, and may be a rational therapy for the treatment of jaundice.PMID:36414211 | DOI:10.1016/j.jep.2022.115943

Nitric Oxide. 2022 Nov 19:S1089-8603(22)00122-7. doi: 10.1016/j.niox.2022.11.003. Online ahead of print.ABSTRACTLimited O2 availability can decrease essential processes in energy metabolism. However, cancers have developed distinct metabolic adaptations to these conditions. For example, glutaminolysis can maintain energy metabolism and hypoxia signaling. Additionally, it has been observed that nitric oxide (NO) possesses concentration-dependent, biphasic effects in cancer. NO has potent anti-tumor effects through modulating events such as angiogenesis and metastasis at low physiological concentrations and inducing cell death at higher concentrations. In this study, Ewing Sarcoma cells (A-673), MIA PaCa, and SKBR3 cells were treated with DetaNONOate (DetaNO) in a model of hypoxia (1% O2) and reoxygenation (21% O2). All 3 cell types showed NO-dependent inhibition of cellular O2 consumption which was enhanced as O2-tension decreased. L-Gln depletion suppressed the mitochondrial response to decreasing O2 tension in all 3 cell types and resulted in inhibition of Complex I activity. In A-673 cells the O2 tension dependent change in mitochondrial O2 consumption and increase in glycolysis was dependent on the presence of L-Gln. The response to hypoxia and Complex I activity were restored by α-ketoglutarate. NO exposure resulted in the A-673 cells showing greater sensitivity to decreasing O2 tension. Under conditions of L-Gln depletion, NO restored HIF-1α levels and the mitochondrial response to O2 tension possibly through the increase of 2-hydroxyglutarate. NO also resulted in suppression of cellular bioenergetics and further inhibition of Complex I which was not rescued by α-ketoglutarate. Taken together these data suggest that NO modulates the mitochondrial response to O2 differentially in the absence and presence of L-Gln. These data suggest a combination of metabolic strategies targeting glutaminolysis and Complex I in cancer cells.PMID:36414197 | DOI:10.1016/j.niox.2022.11.003

Neurosci Lett. 2022 Nov 19:136972. doi: 10.1016/j.neulet.2022.136972. Online ahead of print.ABSTRACTElevated intake of fat modulates L-glutamate (L-Glu) turnover within the hippocampus (HIP). Our aim has been to investigate the effect of saturated vs unsaturated fat on the content of L-Glu and other amino acids involved in synaptic transmission within the HIP. The study was carried out in male mice fed (2 h or 8 weeks) with standard chow or with diets enriched either with saturated (SOLF) or unsaturated triglycerides (UOLF). An in vitro assay was performed in HIP slices incubated with palmitic (PA), oleic (OA), or lauric acid (LA). Amino acids were quantified by capillary electrophoresis. While both diets increased the amount of L-Glu and L-aspartate and decreased L-glutamine levels, only UOLF affected D-serine and taurine levels. γ-Aminobutyric acid was specifically decreased by SOLF. In vitro assays revealed that PA and OA modified L-Glu, glycine, L-serine and D-serine concentration. Our results suggest that fatty acids contained in SOLF and UOLF have an impact on HIP amino acid turnover that may account, at least partially, for the functional changes evoked by these diets.PMID:36414132 | DOI:10.1016/j.neulet.2022.136972

Food Chem. 2022 Nov 10;405(Pt B):134901. doi: 10.1016/j.foodchem.2022.134901. Online ahead of print.ABSTRACTMare milk(MM)production is lower than that of cow milk (CM), making it a premium product. Unfortunately, sellers adulterate MM with cheap CM to unscrupulously gain more profits. This study aimed to analyze MM adulteration with CM using proteomics and metabolomics. Using univariate and multivariate statistical analysis, the relative abundances of certain proteins of caseins and secretoglobin family 1D member were found to be higher with a higher CM admixture percentage. In addition, several metabolites, such as orotic and 4-aminonicotinic acids, increased in the mare-cow milk mixture with an increased CM percentage. Accordingly, these proteins and metabolites distinguished MM adulterated with CM at levels as low as 1 %.These findings can serve as the basis for clarifying the differences at the proteome and metabolome in milk from minor dairy animals and ensure milk authenticity.PMID:36413843 | DOI:10.1016/j.foodchem.2022.134901