PubMed

Related Articles A multi-omic analysis reveals the role of fumarate in regulating the virulence of enterohemorrhagic Escherichia coli. Cell Death Dis. 2018 03 07;9(3):381 Authors: Kuo CJ, Wang ST, Lin CM, Chiu HC, Huang CR, Lee DY, Chang GD, Chou TC, Chen JW, Chen CS Abstract The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infection in vivo remains unclear. Here we show that aerobic metabolism plays an important role in the regulation of EHEC virulence in Caenorhabditis elegans. Our functional genomic analyses showed that disruption of the genes encoding the succinate dehydrogenase complex (Sdh) of EHEC, including the sdhA gene, attenuated its toxicity toward C. elegans animals. Sdh converts succinate to fumarate and links the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) simultaneously. Succinate accumulation and fumarate depletion in the EHEC sdhA mutant cells were also demonstrated to be concomitant by metabolomic analyses. Moreover, fumarate replenishment to the sdhA mutant significantly increased its virulence toward C. elegans. These results suggest that the TCA cycle, ETC, and alteration in metabolome all account for the attenuated toxicity of the sdhA mutant, and Sdh catabolite fumarate in particular plays a critical role in the regulation of EHEC virulence. In addition, we identified the tryptophanase (TnaA) as a downstream virulence determinant of SdhA using a label-free proteomic method. We demonstrated that expression of tnaA is regulated by fumarate in EHEC. Taken together, our multi-omic analyses demonstrate that sdhA is required for the virulence of EHEC, and aerobic metabolism plays important roles in the pathogenicity of EHEC infection in C. elegans. Moreover, our study highlights the potential targeting of SdhA, if druggable, as alternative preventive or therapeutic strategies by which to combat EHEC infection. PMID: 29515100 [PubMed - indexed for MEDLINE]

Related Articles Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect. Annu Rev Food Sci Technol. 2018 03 25;9:227-249 Authors: Corella D, Coltell O, Macian F, Ordovás JM Abstract Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other related diseases. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a critical review of the limitations of the studies undertaken and propose new analyses and greater bioinformatic integration to better understand the most important molecular mechanisms whereby the MedDiet as a whole, or its main food components, may exercise their protective effects. PMID: 29400994 [PubMed - indexed for MEDLINE]

Related Articles Impact of training state on fasting-induced regulation of adipose tissue metabolism in humans. J Appl Physiol (1985). 2018 03 01;124(3):729-740 Authors: Bertholdt L, Gudiksen A, Stankiewicz T, Villesen I, Tybirk J, van Hall G, Bangsbo J, Plomgaard P, Pilegaard H Abstract Recruitment of fatty acids from adipose tissue is increased during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore the aim of the present study was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained [maximal oxygen uptake (V̇o2max) < 45 ml·min-1·kg-1] and trained subjects (V̇o2max > 55 ml·min-1·kg-1) fasted for 36 h, and abdominal subcutaneous adipose tissue biopsies were obtained 2, 12, 24, and 36 h after a standardized meal. Adipose tissue oxidative phosphorylation complexes, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase (PDH)-E1α protein as well as PDH kinase (PDK) 2, PDK4, and PDH phosphatase 2 mRNA content were higher in trained subjects than in untrained subjects. In addition, trained subjects had higher adipose tissue hormone-sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acid concentration than untrained subjects during fasting. Moreover, adipose tissue PDH phosphorylation increased with fasting only in trained subjects. Taken together, trained subjects seem to possess higher basal adipose tissue oxidative capacity as well as higher capacity for regulation of lipolysis and for providing substrate for glyceroneogenesis in adipose tissue during fasting than untrained subjects. NEW & NOTEWORTHY This study shows for the first time higher protein content of lipolytic enzymes and higher oxidative phosphorylation protein in adipose tissue from trained subjects than from untrained subjects during fasting. Furthermore, trained subjects had higher capacity for adipose tissue glyceroneogenesis than untrained subjects. PMID: 29191981 [PubMed - indexed for MEDLINE]

56 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/10/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles The Effect of Temperature on the Stability of In-Use Insulin Pens. Exp Clin Endocrinol Diabetes. 2019 Oct 21;: Authors: Kongmalai T, Preechasuk L, Junnu S, Manocheewa S, Srisawat C, Sriwijitkamol A Abstract BACKGROUND: Improper storage of insulin could decrease its potency. Manufacturers recommend that in-use insulin pens should be kept at between 25-30°C, but room temperature in tropical countries often exceeds this range. This study investigates the effect of temperature on the stability of basal insulin in cartridges 28 days after opening. METHODS: Four different basal insulins were evaluated. Five opened pens of each insulin type were included for each of three storage conditions and 5 unopened insulin pens of each type were stored in the refrigerator as a control. The opened pens were stored for 28 days in either a refrigerator (2-8 °C), at room temperature, or in an incubator (37 °C). Each day insulin pens were mixed 20 times and 2 units were discarded to mimic daily usage. Insulin quantity was evaluated using an ultra-high-performance liquid chromatography assay. RESULTS: The average room temperature during the study period was 29.7 °C. After 28 days, the percentage amount of insulin stored at refrigerator, room temperature or incubator, compared with control was 99.0, 99.7, 101.1% for long-acting insulin; 97.4, 97.2, 99.0% for NPH-1; 101.4, 101.5, 100.7% for NPH-2; and 98.7, 97.8, 98.5% for NPH-3. There were no statistically significant differences. However, we observed a trend toward different stability between clear insulin analog and turbid NPH insulin. CONCLUSIONS: Temperature as high as 37°C and cyclic temperature,had no effect on the stability of in-use insulin pen. PMID: 31634960 [PubMed - as supplied by publisher]

Related Articles Infective juveniles of entomopathogenic nematodes (Steinernema and Heterorhabditis) secrete ascarosides and respond to interspecific dispersal signals. J Invertebr Pathol. 2019 Oct 18;:107257 Authors: Hartley CJ, Lillis PE, Owens RA, Griffin CT Abstract Ascarosides are a modular series of signalling molecules that are widely conserved in nematodes where they function as pheromones with both behavioural and developmental effects. Here we show that the developmentally arrested infective juvenile (IJ) stage of entomopathogenic nematodes (EPN) secrete ascarosides into the surrounding medium. The exometabolome of Steinernema carpocapsae and Heterorhabditis megidis was examined at 0, 1, 7 and 21 days of storage. The concentration of several ascarosides (ascr#11, ascr#9, ascr#12, ascr#1 and ascr#14 for both species, plus ascr#10 for H. megidis) showed a progressive increase over this period, while the concentration of longer chain ascarosides increased up to day 7, with an apparent decline thereafter. Ascr #9 was the main ascaroside produced by both species. Similar ascarosides were found over a 7-day period for Steinernema longicaudum and S. feltiae. Ascaroside blends have previously been shown to promote nematode dispersal. S. carpocapsae and H. megidis IJs were stored for up to 12 weeks and assayed at intervals. IJs where exometabolome was allowed to accumulate showed higher dispersal rates than those where water was changed frequently, indicating that IJ exometabolome maintained high dispersal. Infectivity was not affected. IJ exometabolome accumulated over 7 days promoted dispersal of freshly harvested IJs, both of their own and other EPN species. Similarly, extracts of nematode-infected cadavers promoted dispersal of con- and heterospecific IJs. Thus, IJs are encouraged to disperse from a source cadaver or from other crowded conditions by public information cues, a finding that may have application in enhancing biocontrol. However, the complexity of the ascaroside blend produced by IJs suggests that it may have ecological functions other than dispersal. PMID: 31634473 [PubMed - as supplied by publisher]

Related Articles Translational Medicine: Exercise Physiology Applied to Metabolic Myopathies. Med Sci Sports Exerc. 2019 Nov;51(11):2183-2192 Authors: Grassi B, Porcelli S, Marzorati M Abstract : The relevance of translational medicine (bringing basic science methods "to the bed of patients") is universally recognized. Too often, however, the tools to be applied translationally are thought to derive only from the "-omics" (genomics, proteomics, transcriptomics, metabolomics, etc.) world. The failures of this "reductionist" approach are widely recognized. In the review, we discuss studies demonstrating that scientifically sound mechanistic insights into diseases, relevant both in terms of basic science and clinically, and very well suited to be utilized within a translational medicine approach, can be obtained from the established field of exercise physiology. Methods originally aimed toward basic physiological mechanisms, and applied for the functional evaluation of athletes and sport performance, can have a valuable translational application in patients with metabolic myopathies; such as myophosphorylase deficiency (McArdle disease) or mitochondrial myopathies, diseases which share the common denominator of an impaired skeletal muscle oxidative metabolism. Several variables can yield pathophysiological insights, can identify and quantify the metabolic impairment and the effects on exercise tolerance (one of the main determinants of the patients' clinical picture and quality of life), and can offer diagnostic clues: the impaired capacity of O2 extraction by skeletal muscle, evaluated by near-infrared spectroscopy; the "exaggerated" cardiovascular response to exercise; the slower speed of adjustment of oxidative metabolism during metabolic transitions; the "slow component" of pulmonary O2 uptake kinetics and the associated reduced efficiency and fatigue; the impaired intramuscular matching between O2 delivery and O2 utilization. The proposed methods are noninvasive, and therefore facilitate repeated or serial evaluations. They provide support for a simple message: physiology and physiological research remain the essential link between genes, molecules, and clinical care. PMID: 31634290 [PubMed - in process]

Related Articles Metabolomics-Based Prospective Studies and Prediction of Type 2 Diabetes Mellitus Risks. Metab Syndr Relat Disord. 2019 Oct 21;: Authors: Satheesh G, Ramachandran S, Jaleel A Abstract The preceding decade has witnessed an intense upsurge in the diabetic population across the world making type 2 diabetes mellitus (T2DM) more of an epidemic than a lifestyle disease. Metabolic disorders are often latent for a while before becoming clinically evident, thus reinforcing the pursuit of early biomarkers of metabolic alterations. A prospective study along with metabolic profiling is the most appropriate way to detect the early pathophysiological changes in metabolic diseases such as T2DM. The aim of this review was to summarize the different potential biomarkers of T2DM identified in prospective studies, which used tools of metabolomics. The review also demonstrates on how metabolomic profiling-based prospective studies can be used to address a concern like population-specific disease mechanism. We performed a literature search on metabolomics-based prospective studies on T2DM using the key words "metabolomics," "Type 2 diabetes," "diabetes mellitus", "metabolite profiling," "prospective study," "metabolism," and "biomarker." Additional articles that were obtained from the reference lists of the articles obtained using the above key words were also examined. Articles on dietary intake, type 1 diabetes mellitus, and gestational diabetes were excluded. The review revealed that many studies showed a direct association of branched-chain amino acids and an inverse association of glycine with T2DM. Majority of the prospective studies conducted were targeted metabolomics-based, with Caucasians as their study cohort. The whole disease risk in populations, including Asians, could therefore not be identified. This review proposes the utility of prospective studies in conjunction with metabolomics platform to unravel the altered metabolic pathways that contribute to the risk of T2DM. PMID: 31634052 [PubMed - as supplied by publisher]

Related Articles The mitochondrial deoxyguanosine kinase is required for cancer cell stemness in lung adenocarcinoma. EMBO Mol Med. 2019 Oct 21;:e10849 Authors: Lin S, Huang C, Sun J, Bollt O, Wang X, Martine E, Kang J, Taylor MD, Fang B, Singh PK, Koomen J, Hao J, Yang S Abstract The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK-mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC-mediated therapy resistance and metastatic recurrence. PMID: 31633874 [PubMed - as supplied by publisher]

Related Articles Development of a gas chromatography-mass spectrometry method for breast cancer diagnosis based on nucleoside metabolomes 1-methyl adenosine, 1-methylguanosine, and 8-hydroxy-2'-deoxyguanosine. Biomed Chromatogr. 2019 Oct 21;:e4713 Authors: Omran MM, Rashed RE, Darwish H, Belal AA, Mohamed FZ Abstract Metabolomes are small molecule metabolites (<1000 Da) produced by cellular processes. Metabolomes are close counterparts to the genome, transcriptome, and proteome. The aim of this study was to develop a method to detect and quantify candidate nucleoside metabolomes 1-methyl adenosine (1-MA), 1-methylguanosine (1-MG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine of patients with breast cancer using gas chromatography-mass spectrometry (GC-MS). The method was applied to urine specimens from patients with breast cancer (n=56) and benign breast tumors (n=22), as well as from healthy females (n=20). The relative standard deviations of precision and repeatability analysis were <10%, and recoveries ranged from 88.5% to 105.6%. Limits of detection were 0.014, 0.012, and 0.018 mg/L for 1-MA, 1-MG, and 8-OHdG, respectively. The lower limits of quantitation were 0.056, 0.048, and 0.072 mg/L, respectively. There were significant differences in concentrations of candidate metabolomes between patients with cancer and the healthy individuals, especially for those in the early stages of the disease (p<0.001). No significant differences were observed between the benign and healthy groups. In conclusion, a reliable GC-MS method for detection and quantification of 1-MA, 1-MG, and 8-OHdG metabolomes in urine has been developed. PMID: 31633807 [PubMed - as supplied by publisher]

Related Articles Dimethylaminomicheliolide (DMAMCL) Suppresses the Proliferation of Glioblastoma Cells via Targeting Pyruvate Kinase 2 (PKM2) and Rewiring Aerobic Glycolysis. Front Oncol. 2019;9:993 Authors: Guo J, Xue Q, Liu K, Ge W, Liu W, Wang J, Zhang M, Li QY, Cai D, Shan C, Zhang C, Liu X, Li J Abstract Glioblastoma (GBM) is the most prevalent malignant tumor in the central nervous system. Aerobic glycolysis, featured with elevated glucose consumption and lactate production, confers selective advantages on GBM by utilizing nutrients to support rapid cell proliferation and tumor growth. Pyruvate kinase 2 (PKM2), the last rate-limiting enzyme of glycolysis, is known to regulate aerobic glycolysis, and considered as a novel cancer therapeutic target. Herein, we aim to describe the cellular functions and mechanisms of a small molecular compound dimethylaminomicheliolide (DMAMCL), which has been used in clinical trials for recurrent GBM in Australia. Our results demonstrate that DMAMCL is effective on the inhibition of GBM cell proliferation and colony formation. MCL, the active metabolic form of DMAMCL, selectively binding to monomeric PKM2 and promoting its tetramerization, was also found to improve the pyruvate kinase activity of PKM2 in GBM cells. In addition, non-targeting metabolomics analysis reveals multiple metabolites involved in glycolysis, including lactate and glucose-6-phosphate, are decreased with DMAMCL treatment. The inhibitory effects of DMAMCL are observed to decrease in GBM cells upon PKM2 depletion, further confirming the importance of PKM2 in DMAMCL sensitivity. In conclusion, the activation of PKM2 by DMAMCL results in the rewiring aerobic glycolysis, which consequently suppresses the proliferation of GBM cells. Hence, DMAMCL represents a potential PKM2-targeted therapeutic agent against GBM. PMID: 31632919 [PubMed]

Related Articles The aqueous extract of Lycopus lucidus Turcz exerts protective effects on podocytes injury of diabetic nephropathy via inhibiting TGF-β1 signal pathway. Am J Transl Res. 2019;11(9):5689-5702 Authors: Xie S, Ge F, Yao Y, Zhang W, Wang S, Zhang M, Zhong R, Fang L, Qu D Abstract Diabetic nephropathy (DN) is known as a major microvascular complication leading cause of end-stage renal disease, it generally followed by the process of podocyte fragmentation and detachment. Transforming growth factor β1 (TGF-β1) signaling pathway plays a pivotal role in the initiation and progression of DN. In present study, we aim to investigate the effect of lycopus extracts on podocytes injury and TGF-β signaling. In present study, lycopus extracts treatment abolished the gain in blood glucose and body weight in a dose dependent manner and possessed protective effect on the renal damage, which was indicated by the decreased concentration of Scr, BUN and urine creatinine of serum. Histopathological examination also demonstrated lycopus extracts exert protective effect on renal damage. Western blotting and immunohistochemical results revealed lycopus extracts treatment upregulated the expression of nephrin and down-regulated the expression levels of TGF-β1 and Smad4. Moreover, lycopus extracts treatment suppressed TGF-β1-induced phosphorylation of Smad2/3, ERK1/2 and p38 both in vivo and vitro. In conclusion, lycopus extracts is a novel agent that ameliorate podocytes injury by inhibiting TGF-β signaling pathway and possess potential therapeutic effect on renal damage of DN rats. PMID: 31632540 [PubMed]

Related Articles Microfluidics and Metabolomics Reveal Symbiotic Bacterial-Fungal Interactions Between Mortierella elongata and Burkholderia Include Metabolite Exchange. Front Microbiol. 2019;10:2163 Authors: Uehling JK, Entler MR, Meredith HR, Millet LJ, Timm CM, Aufrecht JA, Bonito GM, Engle NL, Labbé JL, Doktycz MJ, Retterer ST, Spatafora JW, Stajich JE, Tschaplinski TJ, Vilgalys RJ Abstract We identified two poplar (Populus sp.)-associated microbes, the fungus, Mortierella elongata strain AG77, and the bacterium, Burkholderia strain BT03, that mutually promote each other's growth. Using culture assays in concert with a novel microfluidic device to generate time-lapse videos, we found growth specific media differing in pH and pre-conditioned by microbial growth led to increased fungal and bacterial growth rates. Coupling microfluidics and comparative metabolomics data results indicated that observed microbial growth stimulation involves metabolic exchange during two ordered events. The first is an emission of fungal metabolites, including organic acids used or modified by bacteria. A second signal of unknown nature is produced by bacteria which increases fungal growth rates. We find this symbiosis is initiated in part by metabolic exchange involving fungal organic acids. PMID: 31632357 [PubMed]

Related Articles Synergistic Combination of Polymyxin B and Enrofloxacin Induced Metabolic Perturbations in Extensive Drug-Resistant Pseudomonas aeruginosa. Front Pharmacol. 2019;10:1146 Authors: Lin YW, Han ML, Zhao J, Zhu Y, Rao G, Forrest A, Song J, Kaye KS, Hertzog P, Purcell A, Creek D, Zhou QT, Velkov T, Li J Abstract Polymyxins are used as a last-resort class of antibiotics against multidrug-resistant (MDR) Gram-negative Pseudomonas aeruginosa. As polymyxin monotherapy is associated with potential development of resistance, combination therapy is highly recommended. This study investigated the mechanism underlying the synergistic killing of polymyxin B and enrofloxacin against extensive drug-resistant (XDR) P. aeruginosa. An XDR isolate P. aeruginosa 12196 was treated with clinically relevant concentrations of polymyxin B (2 mg/L) and enrofloxacin (1 mg/L) alone or in combination. Metabolome profiles were investigated from bacterial samples collected at 1-and 4-h posttreatment using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and data were analyzed using univariate and multivariate statistics. Significantly perturbed metabolites (q < 0.05, fold change ≥ 2) were subjected to pathway analysis. The synergistic killing by polymyxin B-enrofloxacin combination was initially driven by polymyxin B as indicated by the perturbation of lipid metabolites at 1 h in particular. The killing was subsequently driven by enrofloxacin via the inhibition of DNA replication, resulting in the accumulation of nucleotides at 4 h. Furthermore, the combination uniquely altered levels of metabolites in energy metabolism and cell envelope biogenesis. Most importantly, the combination significantly minimized polymyxin resistance via the inhibition of lipid A modification pathway, which was most evident at 4 h. This is the first study to elucidate the synergistic mechanism of polymyxin B-enrofloxacin combination against XDR P. aeruginosa. The metabolomics approach taken in this study highlights its power to elucidate the mechanism of synergistic killing by antibiotic combinations at the systems level. PMID: 31632279 [PubMed]

Related Articles Closing the Gap Between Therapeutic Use and Mode of Action in Remedial Herbs. Front Pharmacol. 2019;10:1132 Authors: Olivés J, Mestres J Abstract The ancient tradition of taking parts of a plant or preparing plant extracts for treating certain discomforts and maladies has long been lacking a scientific rationale to support its preparation and still widespread use in several parts of the world. In an attempt to address this challenge, we collected and integrated data connecting metabolites, plants, diseases, and proteins. A mechanistic hypothesis is generated when a metabolite is known to be present in a given plant, that plant is known to be used to treat a certain disease, that disease is known to be linked to the function of a given protein, and that protein is finally known or predicted to interact with the original metabolite. The construction of plant-protein networks from mutually connected metabolites and diseases facilitated the identification of plausible mechanisms of action for plants being used to treat analgesia, hypercholesterolemia, diarrhea, catarrh, and cough. Additional concrete examples using both experimentally known and computationally predicted, and subsequently experimentally confirmed, metabolite-protein interactions to close the connection circle between metabolites, plants, diseases, and proteins offered further proof of concept for the validity and scope of the approach to generate mode of action hypotheses for some of the therapeutic uses of remedial herbs. PMID: 31632273 [PubMed]

Related Articles The Immune-Modulator Pidotimod Affects the Metabolic Profile of Exhaled Breath Condensate in Bronchiectatic Patients: A Metabolomics Pilot Study. Front Pharmacol. 2019;10:1115 Authors: D'Amato M, Paris D, Molino A, Cuomo P, Fulgione A, Sorrentino N, Palomba L, Maniscalco M, Motta A Abstract Introduction: Pidotimod, a synthetic dipeptide molecule with biological and immunological activities, is used to reduce the number of exacerbations or pneumonitis in patients with inflammatory diseases. In the present study, we investigated whether Pidotimod modifies the metabolomic pathways measured in the exhaled breath condensate (EBC) of non-cystic fibrosis bronchiectatic patients (NCFB). Materials and Methods: We analyzed 40 adult patients affected by NCFB. They were randomly selected to receive Pidotimod 800 mg b/d for 21 consecutive days (3 weeks) per month for 6 months (20 patients, V1 group) or no drug (20 patients, V0 group), with a 1:1 criterion and then followed as outpatients. Results: EBC samples were collected from all patients at baseline and after 6 months. They were investigated by combined nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analysis to uncover metabolic differences between EBC from NCFB patients before and after therapy with Pidotimod. Pulmonary function test and pulmonary exacerbations were analyzed at baseline and at the end of Pidotimod therapy. The EBC metabolites were all identified, and through statistical evaluation, we were able to discriminate the two samples' classes, with acetate, acetoin, lactate, and citrate as statistically significant discriminatory metabolites. The model vas validated by using a blind set of 20 NCFB samples, not included in the primary analysis. No differences were observed in PFT after 6 months. At the end of the study, there was a significant decrease of exacerbation rate in V1 group as compared with V0 group, with a substantial reduction of the number of mild or severe exacerbations (p < 0.001). Discussion: Pidotimod modifies the respiratory metabolic phenotype ("metabotype") of NCFB patients and reduces the number of exacerbations. PMID: 31632269 [PubMed]

Related Articles Amino Acid-Based Metabolic Indexes Identify Patients With Chronic Obstructive Pulmonary Disease And Further Discriminates Patients In Advanced BODE Stages. Int J Chron Obstruct Pulmon Dis. 2019;14:2257-2266 Authors: Kuo WK, Liu YC, Chu CM, Hua CC, Huang CY, Liu MH, Wang CH Abstract Background: The BODE index is a multidimensional grading system for predicting the prognoses of patients with chronic obstructive pulmonary disease (COPD). This study investigated whether an amino acids-based metabolic profile developed for heart failure patients (including histidine, ornithine, phenylalanine, and leucine) could identify COPD patients and further discriminates COPD patients in advanced BODE stages. Methods: Ultra-performance liquid chromatography was performed on 119 participants, including 75 COPD patients at different BODE stages and 44 normal controls. Albumin, pre-albumin, transferrin, high sensitivity C-reactive protein, and hand grip strength were also measured. Receiver operating characteristic curves and area under curves were used for estimation. Results: The BODE points in our patients were 3.29 [95% confidence interval (CI) = 2.74-3.85]. Compared to normal controls, COPD patients had lower leucine but higher ornithine levels. A COPD score, developed based on leucine and ornithine, significantly discriminated COPD from normal controls [odds ratio (OR) = 2.71, 95% CI = 1.83-4.04, p <0.001]. A COPD score of ≥ 3.00 had an OR of 15.58 (95% CI = 5.96-40.73, p <0.001). In COPD patients from BODE 1 to BODE 4, the levels of histidine, ornithine and phenylalanine increased significantly. In multivariable analysis, histidine and phenylalanine were independently able to distinguish BODE stages 3 and 4 from BODE 1 and were adopted to develop a metabolic score. Metabolic scores identified patients at BODE 3 and 4 (OR = 2.74, 95% CI =1.41-5.29, p = 0.003) better than hand grip strength, high sensitive C-reactive protein, albumin, pre-albumin, and transferrin value. A metabolic score of ≥9.53 significantly discriminated BODE 3 and 4 from BODE 1 and 2 (OR = 8.56, 95% CI = 2.77-26.39, p <0.001). Conclusion: Amino acid-based COPD score and metabolic score discriminate COPD patients from normal controls, and identify patients in advanced stages of COPD. PMID: 31631995 [PubMed - in process]