PubMed

Biomarkers of An Autoimmune Skin Disease - Psoriasis. Genomics Proteomics Bioinformatics. 2015 Sep 8; Authors: Jiang S, Hinchliffe TE, Wu T Abstract Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis is still unclear. Over the last decade, omics-based technologies have been extensively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis. PMID: 26362816 [PubMed - as supplied by publisher]

Metabolomics in rheumatology. Rheumatology (Oxford). 2015 Sep 11; Authors: Kapoor SR, McGrath CM, Fitzpatrick MA, Young SP PMID: 26361880 [PubMed - as supplied by publisher]

Related Articles (1)H NMR metabolomics to study the effects of diazepam on anisatin induced convulsive seizures. J Pharm Biomed Anal. 2015 Sep 1;117:184-194 Authors: Li P, Wei DD, Wang JS, Yang MH, Kong LY Abstract The anticonvulsive properties of diazepam have been extensively studied, mainly focusing on the γ-amino butyrate (GABA) system. The aim of this investigation was to integrally analyze the metabolic events related to neuroprotection of diazepam on anisatin-induced convulsive seizures by a NMR-based metabolomic approach combined with histopathological examination and behavior examination. Multivariate analysis on metabolic profiles of the piriform cortex and cerebellum of mice revealed that diazepam could relieve mice suffering from the convulsive seizures by recovering destructed neurotransmitter and neuromodulator metabolism, ameliorating oxidative stress, alleviating the disturbance in energy, amino acid and nucleic acid metabolism in anisatin intoxicated mice. This integrated metabolomics study provided a powerful and highly effective approach to elucidate therapeutic effects and assessed the safety of diazepam. This study should be helpful for our understanding of convulsive seizures, and provide a holistic view of the treatment effects of benzodiazepine on convulsive seizures. PMID: 26361344 [PubMed - as supplied by publisher]

Related Articles Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. J Cardiol. 2015 Sep 7; Authors: Endo J, Arita M Abstract Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs. PMID: 26359712 [PubMed - as supplied by publisher]

Related Articles Using the matrix-induced ion suppression method for concentration normalization in cellular metabolomics studies. Anal Chem. 2015 Sep 10; Authors: Chen GY, Liao HW, Tsai IL, Tseng YJ, Kuo CH Abstract Studies of the cell metabolome greatly improve our understanding of cell biology. Currently, most cellular metabolomics studies control only cell numbers or protein content without adjusting the total metabolite concentration, mainly because of the lack of an effective concentration normalization method for cell metabolites. This study proposed a matrix-induced ion suppression method (MIIS) to measure the total amount of cellular metabolites by utilizing flow injection analysis coupled with electrospray ionization mass spectrometry (FIA-ESI-MS). We used series dilutions of HL-60 cell extracts to establish the relationship between cellular metabolite concentration and the degree of ion suppression of the ion suppression indicator, and a good correlation was obtained between 2- to 12-fold dilutions of cell extracts (R2 = 0.999). Two lung cancer cells, CL1-0 and CL1-5, were selected as the model cell lines to evaluate the efficacy of the MIIS method and the importance of metabolite concentration normalization. Through MIIS analysis, CL1-0 cells were found to contain metabolites at a concentration 2.1 times higher than in CL1-5, and the metastatic properties of CL1-5 could only be observed after 2.1-fold dilution of CL1-0 before metabolomic analysis. Our results demonstrated that the MIIS method is an effective approach for metabolite concentration normalization and that controlling metabolite concentrations can improve data integrity in cellular metabolomics studies. PMID: 26359637 [PubMed - as supplied by publisher]

Related Articles [Application and research advances of metabolomics in the field of orthopedics]. Zhonghua Wai Ke Za Zhi. 2015 Jun;53(6):476-80 Authors: Sun Z, Qiu G, Zhao Y Abstract Metabolomics is a subject of systematic, qualitative and quantitative analysis of all metabolites in all organisms, which is applied to finding biomarkers and studying pathogenesis of diseases. Study procedures of metabolomics include data acquisition by spectroscopic/spectrometric techniques, multivariate statistical analysis and projection of the acquired metabolomic information. In recent years, metabolomics have gained popularity in orthopedic field. Metabolomic study of osteoarthritis was firstly conducted and widely developed. Metabolite profiles of different samples, including serum/plasma, urine, synovial fluid and synovial tissue, were studied and dozens of differential metabolites and several disturbed metabolic pathways were found. In addition, metabolomic studies of osteoporosis, ankylosing spondylitis and bone tumors were also conducted, which identified many potential biomarkers and made further understanding of pathogenesis of corresponding disease. However, metabolomic studies in orthopedic field just begin. More orthopedic diseases will be researched thank to the satisfactory results of previous reports. PMID: 26359065 [PubMed - in process]

Related Articles Recent Advances and Applications of Metabolomics to Investigate Neurodegenerative Diseases. Int Rev Neurobiol. 2015;122:95-132 Authors: Ibáñez C, Cifuentes A, Simó C Abstract Metabolomics is gaining an important role in the investigation of neurological pathologies such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis which are characterized by the absence of reliable diagnostic markers. The magnitude of emotional, physical, and financial burden related to these three devastating pathologies can be deduced considering that nearly 20 million people worldwide suffer from these three pathologies. In this chapter, an overview of the recent advances and applications of metabolomics to investigate these major neurodegenerative diseases will be presented. Metabolomics strategies are now being developed to map potential perturbations in biochemical pathways linked to neurodegeneration. Going further, there is more and more evidence supporting the concept that these pathologies can begin years or even decades before the onset of clinical symptoms, and thus, metabolomics is also increasingly being used to discover preclinical biomarkers of these neurological diseases. PMID: 26358892 [PubMed - in process]

Related Articles Parkinson's Disease: In Vivo Brain Metabolomics by MRS. Int Rev Neurobiol. 2015;122:81-94 Authors: Rango M Abstract In vivo brain metabolomics in Parkinson's disease is still in its infancy. This chapter will review brain metabolomics in the human brain as studied noninvasively by magnetic resonance spectroscopy. Although preliminary, the results shed some light on the pathophysiology of Parkinson's disease. PMID: 26358891 [PubMed - in process]

Related Articles Metabolomics of Neurodegenerative Diseases. Int Rev Neurobiol. 2015;122:53-80 Authors: Botas A, Campbell HM, Han X, Maletic-Savatic M Abstract Neurodegenerative diseases are progressive, devastating, and terminal, carrying both personal and societal burden. Currently, their diagnosis depends on their clinical presentation. No quantitative biomarkers exist to enable early verdict and commencement of therapy. The lack of diagnostic biomarkers stems from the unavailability of brain tissue, the complexity and heterogeneity of the brain and neurodegenerative pathology, and the fact that peripheral tissues such as blood, urine, and even cerebrospinal fluid might not reflect early stages of brain pathology. Moreover, accumulated evidence indicates the majority of these diseases are not genetically inherited; rather, the genes bring about the risk to develop them, but the trigger is not known. As metabolites are at the intersection between the genetic background of a cell or a tissue and the environmental effects on the same, metabolomics has emerged as a field with great promise to deliver new, biologically, and clinically relevant biomarkers for neurodegenerative disorders. Here, we review the basic principles of metabolomics and focus on studies performed in most common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, Multiple sclerosis, and Amyotrophic lateral sclerosis. PMID: 26358890 [PubMed - in process]

Related Articles Lipidomics: novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease. Chem Biol Interact. 2015 Sep 7; Authors: Zhao YY, Miao H, Cheng XL, Wei F Abstract The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. PMID: 26358168 [PubMed - as supplied by publisher]

Related Articles Reference Standardization for Mass Spectrometry and High-Resolution Metabolomics Applications to Exposome Research. Toxicol Sci. 2015 Sep 9; Authors: Go YM, Walker DI, Liang Y, Uppal K, Soltow QA, Tran V, Strobel F, Quyyumi AA, Ziegler TR, Pennell KD, Miller GW, Jones DP Abstract The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including exposures from the environment, diet, behavior, and endogenous processes. A major challenge for exposome research lies in the development of robust and affordable analytic procedures to measure the broad range of exposures and associated biologic impacts occurring over a lifetime. Biomonitoring is an established approach to evaluate internal body burden of environmental exposures, but use of biomonitoring for exposome research is often limited by the high costs associated with quantification of individual chemicals. High-resolution metabolomics (HRM) uses ultra-high resolution mass spectrometry with minimal sample preparation to support high-throughput relative quantification of thousands of environmental, dietary and microbial chemicals. HRM also measures metabolites in most endogenous metabolic pathways, thereby providing simultaneous measurement of biologic responses to environmental exposures. The present research examined quantification strategies to enhance the usefulness of HRM data for cumulative exposome research. The results provide a simple reference standardization protocol in which individual chemical concentrations in unknown samples are estimated by comparison to a concurrently analyzed, pooled reference sample with known chemical concentrations. The approach was tested using blinded analyses of amino acids in human samples and was found to be comparable to independent laboratory results based on surrogate standardization or internal standardization. Quantification was reproducible over a 13-month period and extrapolated to thousands of chemicals. The results show that reference standardization protocol provides an effective strategy that will enhance data collection for cumulative exposome research. In principle, the approach can be extended to other types of mass spectrometry and other analytical methods. PMID: 26358001 [PubMed - as supplied by publisher]

Related Articles OnSet: A Visualization Technique for Large-scale Binary Set Data. IEEE Trans Vis Comput Graph. 2014 Dec;20(12):1993-2002 Authors: Sadana R, Major T, Dove A, Stasko J Abstract Visualizing sets to reveal relationships between constituent elements is a complex representational problem. Recent research presents several automated placement and grouping techniques to highlight connections between set elements. However, these techniques do not scale well for sets with cardinality greater than one hundred elements. We present OnSet, an interactive, scalable visualization technique for representing large-scale binary set data. The visualization technique defines a single, combined domain of elements for all sets, and models each set by the elements that it both contains and does not contain. OnSet employs direct manipulation interaction and visual highlighting to support easy identification of commonalities and differences as well as membership patterns across different sets of elements. We present case studies to illustrate how the technique can be successfully applied across different domains such as bio-chemical metabolomics and task and event scheduling. PMID: 26356913 [PubMed - in process]

Related Articles Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Sci Transl Med. 2015 Sep 9;7(304):304re7 Authors: Boden G, Homko C, Barrero CA, Stein TP, Chen X, Cheung P, Fecchio C, Koller S, Merali S Abstract Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance. However, they may be late events that only develop after chronic excessive nutrient intake. The nature of the initial event that produces insulin resistance at the beginning of excess caloric intake and weight gain remains unknown. We show that feeding healthy men with ~6000 kcal/day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 days) of systemic and adipose tissue insulin resistance and oxidative stress but no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in extensive oxidation and carbonylation of numerous proteins, including carbonylation of GLUT4 near the glucose transport channel, which likely resulted in loss of GLUT4 activity. These results suggest that the initial event caused by overnutrition may be oxidative stress, which produces insulin resistance, at least in part, via carbonylation and oxidation-induced inactivation of GLUT4. PMID: 26355033 [PubMed - in process]

Related Articles Biosynthesis and Biotechnology of High-Value p-Menthane Monoterpenes, Including Menthol, Carvone, and Limonene. Adv Biochem Eng Biotechnol. 2015;148:319-53 Authors: Lange BM Abstract Monoterpenes of the p-menthane group are volatile secondary (or specialized) metabolites found across the plant kingdom. They are dominant constituents of commercially important essential oils obtained from members of the genera Mentha (Lamiaceae), Carum (Apiaceae), Citrus (Rutaceae), and Eucalyptus (Myrtaceae). p-Menthane monoterpenes have also attracted interest as chiral specialty chemicals, and the harvest from natural sources is therefore supplemented by chemical synthesis. More recently, microbial and plant-based platforms for the high-level accumulation of specific target monoterpenes have been developed. In this review chapter, I discuss the properties of the genes and enzymes involved in p-menthane biosynthesis and provide a critical assessment of biotechnological production approaches. PMID: 25618831 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of epithelial ovarian cancer cell lines: evaluation of harvesting protocols for profiling using NMR spectroscopy. Bioanalysis. 2015;7(2):157-66 Authors: Engskog M, Björklund M, Haglöf J, Arvidsson T, Shoshan M, Pettersson C Abstract BACKGROUND: Metabolic profiling represents a novel technology for analyzing tumor cells. Epithelial ovarian carcinoma has a low survival rate due to the development of aggressive and chemotherapy-resistant cells. A tailored and reliable protocol is presented for profiling of chemoresistant cells using the cell line SKOV3 and a multiresistant subline SKOV3R. RESULTS: Harvesting protocols with cold methanol or MilliQ freeze/thaw cycles were compared. Increased reproducibility using MilliQ was evidenced. Importantly, both approaches resulted in similar profiles. Compared with parental SKOV3, the SKOV3R cells showed a significantly different profile. CONCLUSION: The MilliQ protocol is preferred owing to higher reproducibility and increased sample preparation options. The resulting metabolic profiles summarize metabolic alterations in chemoresistant cells consistent with a progressed and aggressive phenotype. PMID: 25587833 [PubMed - indexed for MEDLINE]

Related Articles Metabolism, distribution, and excretion of deoxynivalenol with combined techniques of radiotracing, high-performance liquid chromatography ion trap time-of-flight mass spectrometry, and online radiometric detection. J Agric Food Chem. 2014 Jan 8;62(1):288-96 Authors: Wan D, Huang L, Pan Y, Wu Q, Chen D, Tao Y, Wang X, Liu Z, Li J, Wang L, Yuan Z Abstract Dispositions of deoxynivalenol (DON) in rats and chickens were investigated, using a radiotracer method coupled with a novel γ-accurate radioisotope counting (γ-ARC) radio-high-performance liquid chromatography ion trap time-of-flight tandem mass spectrometry (radio-HPLC-IT-TOF-MS/MS) system. 3β-(3)H-DON was chemically synthesized and orally administrated to both sexes of rats and chickens as single or multiple doses. The results showed that DON was widely distributed and quickly eliminated in all tissues. The highest concentration was found in the gastrointestinal tract at 6 h post-administration. Substantially lower levels were detected in the kidney, liver, heart, lung, spleen, and brain. Three new metabolites were identified tentatively as 10-deoxynivalenol-sulfonate, 10-deepoxy-deoxynivalenol (DOM-1)-sulfonate, and deoxynivalenol-3α-sulfate. Deoxynivalenol-3α-sulfate was a major metabolite in chickens, while the major forms in rats were DOM-1 and DON. Additionally, a higher excretion rate in urine was observed in female rats than in male rats. The differences in metabolite profiles and excretion rates, which suggested diverse ways to detoxify, may relate to the different tolerances in different genders or species. PMID: 24341775 [PubMed - indexed for MEDLINE]

"Omics" insights into PAH degradation toward improved green remediation biotechnologies. Environ Sci Technol. 2015 Sep 9; Authors: El Amrani A, Dumas AS, Wick LY, Yergeau E, Berthomé R Abstract This review summarises recent knowledge of polycyclic aromatic hydrocarbons (PAHs) biotransformation by microorganisms and plants. Whereas most research has focused on PAH degradation either by plants or microorganisms separately, this review specifically addresses the interactions of plants with their rhizosphere microbial communities. Indeed, plant roots release exudates that contain various nutritional and signalling molecules that influence bacterial and fungal populations. The complex interactions of these populations play a pivotal role in the biodegradation of high-molecular-weight PAHs and other complex molecules. Emerging integrative approaches, such as (meta-) genomics, (meta-) transcriptomics, (meta-) metabolomics, and (meta-) proteomics studies are discussed, emphasising how "omics" approaches bring new insight to decipher molecular mechanisms of PAH degradation both at the single species and community levels. Such knowledge address new pictures on how organic molecules are co-metabolically degraded in a complex ecosystem and should help in setting up novel decontamination strategies based on the rhizosphere interactions between plants and their microbial associates. PMID: 26352597 [PubMed - as supplied by publisher]

A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence. Nature. 2015 Sep 9; Authors: Rajniak J, Barco B, Clay NK, Sattely ES Abstract Thousands of putative biosynthetic genes in Arabidopsis thaliana have no known function, which suggests that there are numerous molecules contributing to plant fitness that have not yet been discovered. Prime among these uncharacterized genes are cytochromes P450 upregulated in response to pathogens. Here we start with a single pathogen-induced P450 (ref. 5), CYP82C2, and use a combination of untargeted metabolomics and coexpression analysis to uncover the complete biosynthetic pathway to 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), a previously unknown Arabidopsis metabolite. This metabolite harbours cyanogenic functionality that is unprecedented in plants and exceedingly rare in nature; furthermore, the aryl cyanohydrin intermediate in the 4-OH-ICN pathway reveals a latent capacity for cyanogenic glucoside biosynthesis in Arabidopsis. By expressing 4-OH-ICN biosynthetic enzymes in Saccharomyces cerevisiae and Nicotiana benthamiana, we reconstitute the complete pathway in vitro and in vivo and validate the functions of its enzymes. Arabidopsis 4-OH-ICN pathway mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with a role in inducible pathogen defence. Arabidopsis has been the pre-eminent model system for studying the role of small molecules in plant innate immunity; our results uncover a new branch of indole metabolism distinct from the canonical camalexin pathway, and support a role for this pathway in the Arabidopsis defence response. These results establish a more complete framework for understanding how the model plant Arabidopsis uses small molecules in pathogen defence. PMID: 26352477 [PubMed - as supplied by publisher]

Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality. PLoS Genet. 2015 Sep;11(9):e1005487 Authors: Raffler J, Friedrich N, Arnold M, Kacprowski T, Rueedi R, Altmaier E, Bergmann S, Budde K, Gieger C, Homuth G, Pietzner M, Römisch-Margl W, Strauch K, Völzke H, Waldenberger M, Wallaschofski H, Nauck M, Völker U, Kastenmüller G, Suhre K Abstract Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. PMID: 26352407 [PubMed - as supplied by publisher]

Biochemical characterization of embryogenic calli of Vanilla planifolia in response to two years of thidiazuron treatment. Plant Physiol Biochem. 2015 Aug 28;96:337-344 Authors: Kodja H, Noirot M, Khoyratty SS, Limbada H, Verpoorte R, Palama TL Abstract Vanilla planifolia embryogenic calli were cultured for two years on a medium containing thidiazuron (TDZ). Due to the presence of TDZ, these calli were under permanent chemical treatment and the differentiation of adventitious shoots from protocorm-like-bodies (PLBs) was blocked. When embryogenic calli were transferred onto a medium without TDZ, shoot organogenesis and plantlet regeneration occurred. To gain better knowledge about the biochemical and molecular processes involved in the morphoregulatory role of TDZ, hormonal and metabolomic analyses were performed. Our results indicate that in the presence of TDZ, embryogenic calli contained a high amount of abscisic acid (ABA) essentially metabolized into abscisic acid glucosyl ester (ABAGE) and phaseic acid (PA), which was the most abundant. When transferred onto a medium without TDZ, shoot regeneration and development take place in four stages that include: embryogenic calli growth, differentiation of PLBs from meristmatic cells zones (MCZ), shoot organogenesis from PLBs and the elongation of well-formed shoots. From a hormonal perspective, the significant reduction in ABA metabolism and its readjustment in the ABAGE pathway triggered PLBs formation. However, this first morphogenesis was stimulated by a strong reduction in IAA metabolism. The organogenesis of PLBs into shoots is associated with an increase in ABA catabolism and a gradual shift in cellular metabolism towards shoot differentiation. Thus, the initiation of the elongation process in shoots is correlated with an alteration in metabolite composition, including an increase in energy reserves (sucrose/starch) and a rapid decrease in alanine content. Our data highlighted the relationship between endogenous hormone signalling, carbohydrate metabolism and shoot organogenesis in Orchid plants. PMID: 26351150 [PubMed - as supplied by publisher]