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Organic agriculture is considered one of the elements of sustainable food production and consumption, mainly due to its limited impact on the natural environment. At the same time, the quality features of organically produced foods, especially sensory attributes and health promoting values, are important factors determining consumers’ interest, and therefore play a key role in the organic sector’s development. The aim of this study was to investigate the sensory characteristics and concentrations of sugars and selected health-promoting bioactive compounds of organic courgette compared to conventionally grown courgette. In addition, untargeted metabolomic analysis of the courgette fruits was performed. The results of this study did not show a significant effect of the horticultural system (organic vs. conventional) on the concentrations of vitamin C, carotenoids, and chlorophylls in the courgette fruits. However, the fruits from the organic systems were significantly richer in sugars when compared to the conventionally cultivated ones (p = 0.038). Moreover, the organic fruits fertilized with manure contained significantly higher amounts of polyphenols, including gallic acid (p = 0.016), chlorogenic acid (p = 0.012), ferulic acid (p = 0.019), and quercetin-3-O-rutinoside (p = 0.020) compared to the conventional fruits. The untargeted analysis detected features significantly differentiating courgette fruits depending on the cultivar and horticultural system. Some significant differences in sensory values were also identified between fruits representing the two cultivars and coming from the horticultural systems compared in the study. Conventional courgettes were characterized by the most intensive peel color and aquosity, but at the same time were the least hard and firm compared to the fruits from the two organic systems. There was also a trend towards higher overall quality of the organically grown fruits. The presented study shows that the organic and conventional courgette fruits differ in a number of quality features which can influence consumers’ health and purchasing choices.

Organic agriculture is considered one of the elements of sustainable food production and consumption, mainly due to its limited impact on the natural environment. At the same time, the quality features of organically produced foods, especially sensory attributes and health promoting values, are important factors determining consumers’ interest, and therefore play a key role in the organic sector’s development. The aim of this study was to investigate the sensory characteristics and concentrations of sugars and selected health-promoting bioactive compounds of organic courgette compared to conventionally grown courgette. In addition, untargeted metabolomic analysis of the courgette fruits was performed. The results of this study did not show a significant effect of the horticultural system (organic vs. conventional) on the concentrations of vitamin C, carotenoids, and chlorophylls in the courgette fruits. However, the fruits from the organic systems were significantly richer in sugars when compared to the conventionally cultivated ones (p = 0.038). Moreover, the organic fruits fertilized with manure contained significantly higher amounts of polyphenols, including gallic acid (p = 0.016), chlorogenic acid (p = 0.012), ferulic acid (p = 0.019), and quercetin-3-O-rutinoside (p = 0.020) compared to the conventional fruits. The untargeted analysis detected features significantly differentiating courgette fruits depending on the cultivar and horticultural system. Some significant differences in sensory values were also identified between fruits representing the two cultivars and coming from the horticultural systems compared in the study. Conventional courgettes were characterized by the most intensive peel color and aquosity, but at the same time were the least hard and firm compared to the fruits from the two organic systems. There was also a trend towards higher overall quality of the organically grown fruits. The presented study shows that the organic and conventional courgette fruits differ in a number of quality features which can influence consumers’ health and purchasing choices.

Background Although oocyte quality is the dominant factor determining embryo quality, few studies have been conducted to evaluate embryo quality based on the metabolites related to the oocyte. With quantification of the follicular fluid (FF) metabolites, in assisted reproductive technology (ART), this study sought to evaluate the embryo or oocyte quality through an informative approach. Results An evaluation model consisting of 17 features was generated to distinguish the embryo quality on day 3 post-fertilization, and phosphatidylcholines (PCs) were the key contributors to the evaluation. The model was extended to the patients under different ages and hyperstimulations, and the features were further enriched to facilitate the evaluation of the embryo quality. The metabolites were clustered through pathway analysis, leading to a hypothesis that accumulation of arachidonic acid induced by PCs might weaken embryo quality on day 3 post-fertilization. Conclusions A discriminating model with metabolic features elicited from follicular fluid was established, which enabled the evaluation of the embryo or oocyte quality even under certain clinical conditions, and the increase of PCs in follicular fluid implies the attenuation of embryo quality on day 3 post-fertilization.

Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward current. Moreover, ranolazine has other metabolic features which makes it effective in other diseases as well as coronary artery ones. In this paper I make an updated review of all possible therapeutic roles of ranolazine: through cardiology and beyond.

Immunity and metabolism are interdependent and coordinated, which are the core mechanisms for the body to maintain homeostasis. In tumor immunology research, immunometabolism has been a research hotspot and has achieved groundbreaking changes in recent years. However, in the field of maternal-fetal medicine, research on immunometabolism is still lagging. Reports directly investigating the roles of immunometabolism in the endometrial microenvironment and regulation of maternal-fetal immune tolerance are relatively few. This review highlights the leading techniques used to study immunometabolism and their development, the immune cells at the maternal-fetal interface and their metabolic features required for the implementation of their functions, explores the interaction between immunometabolism and pregnancy regulation based on little evidence and clues, and attempts to propose some new research directions and perspectives.

Extracting metabolic features from liquid chromatography-mass spectrometry (LC-MS) data relies on the recognition of extracted ion chromatogram (EIC) peak shapes using peak picking algorithms. Unfortunately, all peak picking algorithms present a significant drawback of generating a problematic number of false positives. In this work, we take advantage of deep learning technology to develop a convolutional neural network (CNN)-based program that can automatically recognize metabolic features with poor EIC shapes, which are of low feature fidelity and more likely to be false. Our CNN model was trained using 25095 EIC plots collected from 22 LC-MS-based metabolomics projects of various sample types, LC and MS conditions. Notably, we manually inspected all the EIC plots to assign good or poor EIC quality for accurate model training. The trained CNN model is embedded into a C#-based program, named EVA (short for evaluation). The EVA Windows Application is a versatile platform that can process metabolic features generated by LC-MS systems of various vendors and processed using various data processing software. Our comprehensive evaluation of EVA indicates that it achieves over 90% classification accuracy. EVA can be readily used in LC-MS-based metabolomics projects and is freely available on the Microsoft Store by searching "EVA Metabolomics".

Metabolic reprogramming is a hallmark of cancer initiation, progression, and relapse. From the initial observation that cancer cells preferentially ferment glucose to lactate, termed the Warburg effect, to emerging evidence indicating that metabolic heterogeneity and mitochondrial metabolism are also important for tumor growth, the complex mechanisms driving cancer metabolism remain vastly unknown. These unique shifts in metabolism must be further investigated in order to identify unique therapeutic targets for individuals afflicted by this aggressive disease. Although novel therapies have been developed to target metabolic vulnerabilities in a variety of cancer models, only limited efficacy has been achieved. In particular, lung cancer metabolism has remained relatively understudied and underutilized for the advancement of therapeutic strategies, however recent evidence suggests that lung cancers have unique metabolic preferences of their own. This review aims to provide an overview of essential metabolic mechanisms and potential therapeutic agents in order to increase evidence of targeted metabolic inhibition for the treatment of lung cancer, where novel therapeutics are desperately needed.

Summary Metabolism during pregnancy is a dynamic and precisely programmed process, the failure of which can bring devastating consequences to the mother and fetus. To define a high-resolution temporal profile of metabolites during healthy pregnancy, we analyzed the untargeted metabolome of 784 weekly blood samples from 30 pregnant women. Broad changes and a highly choreographed profile were revealed: 4,995 metabolic features (of 9,651 total), 460 annotated compounds (of 687 total), and 34 human metabolic pathways (of 48 total) were significantly changed during pregnancy. Using linear models, we built a metabolic clock with five metabolites that time gestational age in high accordance with ultrasound (R = 0.92). Furthermore, two to three metabolites can identify when labor occurs (time to delivery within two, four, and eight weeks, AUROC ≥ 0.85). Our study represents a weekly characterization of the human pregnancy metabolome, providing a high-resolution landscape for understanding pregnancy with potential clinical utilities., Graphical Abstract, Highlights • Weekly metabolome of maternal blood changes dynamically through healthy pregnancy • A metabolic clock of five blood metabolites accurately predicts gestational age • Two to three metabolites identify labor onset within two, four, and eight weeks • Women with metabolic clocks that outpaced ultrasound evaluation tend to deliver earlier, Identification of blood metabolites in pregnant women that can accurately predict gestational age and provide insights into pregnancy variations undetected by ultrasound.

Summary. Generalized periodontitis is one of the most common and complex problems of modern dentistry. According to the WHO, its incidence corrects with age: in the group of individuals from 35 to 44 years, the prevalence of this pathology reaches more than 50 %, in people older than 65–78%, which leads to tooth loss in 40 % of cases. The complexity of the problem lies in the fact that generalized periodontitis is a multifactorial disease, which is characterized by a chronic course with a periodic exacerbation of the inflammatory process in periodontal disease. The progression of destructive phenomena in periodontal tissues depends on many reasons, the role of which from the moment of description and to this day remains the subject of debate and debate. The aim of this study is to assess the pathogenetic significance of disorders of the local components of the immune system, cytokine profile, processes of radical and antioxidant status, and features of bone remodeling in patients with aggressive generalized periodontitis. The work is based on the results of comprehensive clinical and laboratory studies of 123 patients with different course of generalized periodontitis. The study used generally accepted clinical, paraclinical and laboratory research methods, supplemented by dental volumetric tomography. The subjects were divided into 2 groups: I – with an aggravated course (62 people), II – with an aggressive (rapidly progressing) course of the disease (61 people), the control group consisted of 20 healthy volunteers. Studies have shown that exacerbated and rapidly progressing chronic generalized periodontitis is manifested by the same type of clinical symptoms and the same state of gingival and periodontal indices. In individuals with a high rate of destruction of periodontal bone structures, the activity of the inflammatory-destructive process and the rate of loss of periodontal bone tissue are caused by functional disorders of varying strengths: the state of local secretory immunity, the processes of free radical oxidation and the antioxidant defense system, changes in the cytokine profile, and is also found bone remodeling dysfunction due to increased processes of bone resorption and decreased bone formation. The need is substantiated, along with anamnestic data, to take into account the degree of increase in the levels of proinflammatory cytokines IL-1β and TNF-α, as well as features of bone metabolism and osteoparotic processes detected using dental volumetric tomography.

Going forward, industrial biotechnology must consider non-model metabolic engineering platforms if it is to have maximal impact. This will include microorganisms that natively possess strategic physiological and metabolic features but lack either molecular genetic tools or such tools are rudimentary, requiring further development. If non-model platforms are successfully deployed, new avenues for production of fuels and chemicals from renewable feedstocks or waste materials will emerge. Here, the challenges and opportunities for extreme thermophiles as metabolic engineering platforms are discussed.

Millions of children have multiple nutritional deficiencies, threatening their optimal growth, development, and quality of life. Revealing the magnitude and underlying biology of malnutrition from a greatly expanded set of practical biomarkers will be critical for developing appropriately targeted and evaluated interventions. However, our abilities to reveal and quantify the many forms of malnutrition, other than by anthropometry and occasional use of biochemical indicators, remain limited. Plasma proteomics holds great promise as a basis for developing novel biomarkers to facilitate assessment of growth, micronutrient status, inflammation, and other health status of populations while also providing biological insight into causes and adverse consequences of malnutrition. Discovery-driven plasma proteomics has been shown to reveal functional biomarkers of nutritional and health status, identifying clusters of protein biomarkers from which field-friendly, comprehensive, and low-cost methods could be developed for assessing populations. In this brief review, we summarize several key discoveries to date and discuss potential public health applications of proteomics-based biomarkers in reporting the extent and metabolic features of undernutrition in low-resource settings.

Psychological suboptimal health state (PSHS), a subtype of suboptimal health status (SHS), seriously threatens the physical and mental health of human beings. Baihe Dihuang Tang (BDT), a traditional Chinese medicine prescription, has been used to improve PSHS in clinical and achieve significant efficacy for a long time. Exploring of the underlying mechanism of BDT improving the state of PSHS is of significant importance. In the present work, all subjects were screened in strict accordance with inclusion and exclusion criteria. the UHPLC-Q Exactive Orbitrap-MS and Trace GC-PolarisQ Mass were performed to analyze the metabolic features of BDT improving the state of PSHS. Combined with the experimental results of metabolomics and the predicted results of network pharmacology, the metabolic biological network was constructed to find the potential targets of BDT intervention on PSHS. Finally, A total of 22 differential metabolites have been identified in PSHS group. 15 plasma biomarkers were significantly regulated by BDT. The results indicated that the BDT decoction is of a significant therapeutic effect on the improvement of PSHS primarily through regulating pyruvate metabolism and phenylalanine metabolism. Moreover, it is possible for BDT to improve PSHS through the functional targets including GLO1, MAOA and MAOB, which are closely related to monoamine neurotransmitters. Here, these approaches provide a tractable, powerful tool for understanding the underlying mechanism elucidating of BDT for PSHS management.

Background: Hypophosphatemic rickets is a rare disease, related to renal phosphate waste, which cause bone deformities, and lead to walking abnormalities and to the reduction in the quality of life. Clinical recommendations in different countries vary in medications, recommended doses and surgery approach. The main aim was to analyze phosphate metabolism in children with hypophosphatemic rickets and to evaluate results of conservative and surgical therapy. Methods: We analyzed medical histories of 15 children with hypophosphatemic rickets and investigated phosphate metabolism, including the measurement of serum intact fibroblast growth factor 23 and X-ray bone densitometry. Routine biochemical tests were assessed with our laboratory reference data, the level of iFGF-23 in hypophosphatemic children was compared with the same values in 18 healthy children. Results: We investigated 15 girls with hypophosphatemic rickets, aged of from 3 years 9 months to 18 years 7 months. All children were treated with alphacalcidol and inorganic phosphate (in dose from 16.21 to 103.3 mg/kg, during from 1 to 114 months). Eleven (73%) children had surgical correction of bone deformations, starting at the age of from 3 to 12 years. Ten (91%) of them had the relapse of bone deformations. Two of four children undergone to the correction of bone abnormalities on alphacalcidol and phosphate therapy without surgery. The level of iFGF-23 in children with hypophosphatemic rickets was 73.11 pg/ml, and exceed iFGF-23 in control group (22.92 pg/ml), p =0,009. Conclusion: Early surgical treatment of bone deformations is not indicated in hypophosphatemic rickets because of risk of recurrence, observed in 91% of our patients. There could be spontaneous correction of bone deformation during conservative therapy, when it is started early.

Chronic adenine feeding is extensively used to develop animal models of chronic renal failure with metabolic features resembling those observed in humans. However, the mechanism by which adenine induces renal failure is poorly understood. In this study, we examined the early effects of adenine on water metabolism and salt balance in rats placed in metabolic cages and fed control or adenine-containing diets for 7 days. Molecular and functional studies demonstrated that adenine-fed rats exhibited a significant reduction in food intake, polyuria, polydipsia, decreased urine osmolality, and increased salt wasting. These effects are independent of changes in food intake and result from a coordinated downregulation of water channel aquaporin-2 (AQP2) and salt transporter (Na+-K+-Cl−cotransporter 2; NKCC2) in the collecting duct and medullary thick ascending limb, respectively. As a result, adenine-fed rats exhibited massive volume depletion, as indicated by a significant body weight loss, increased blood urea nitrogen, and increased hematocrit and hemoglobin levels, all of which were significantly corrected with NaCl replacement. Adenine-induced urinary concentrating defect was not corrected by exogenous arginine vasopressin (AVP), and it correlated with reduced cAMP production in vivo and in vitro. In conclusion, adenine acts on renal tubules as a signaling molecule and causes nephrogenic diabetes insipidus with salt wasting, at least, by directly interfering with AVP V2 receptor signaling with subsequent downregulation of NKCC2 and AQP2 in the kidney. The combination of renal fluid loss and decreased food intake with subsequent massive volume depletion likely plays an important role in the development of early prerenal failure that progresses to chronic kidney disease in long-term adenine feeding.

The “ideal” graft for forming outflow ways is a big issue in reconstructive heart valve surgery. For today, this question is a field of interest especially in pediatric cardiac surgery, because the existing prosthesis are exposed to aggressive degenerative processes due to metabolic features, and also do not have the growth potential. Therefore, repetitive graft reimplantation gradually increases risk of surgery and greatly reduce the quality of patient’s life. Tissue engineering is a new perspective approach in surgery of congenital and heart valve diseases, which may help overcome limitations of existing and provide the new opportunities for surgical correction. This review highlights current trends in development of tissue-engineered heart valves and grafts, and existing limitations and potential solutions are discussed.

Adipose tissue plays a pivotal role in energy storage, hormone secretion, and temperature control. Mammalian adipose tissue is largely divided into white adipose tissue and brown adipose tissue, although recent studies have discovered the existence of beige adipocytes. Adipose tissues are widespread over the whole body and each location shows distinctive metabolic features. Mice are used as a representative experimental model system in metabolic studies due to their numerous advantages. Importantly, the adipose tissues of experimental animals and humans are not perfectly matched, and each adipose tissue exhibits both similar and specific characteristics. Nevertheless, the diversity and characteristics of mouse adipose tissue have not yet been comprehensively summarized. This review summarizes diverse information about the different types of adipose tissue being studied in mouse models. The types and characteristics of adipocytes were described, and each adipose tissue was classified by type, and features such as its distribution, origin, differences from humans, and metabolic characteristics were described. In particular, the distribution of widely studied adipose tissues was illustrated so that researchers can comprehensively grasp its location. Also, the adipose tissues misused or confusingly used among researchers were described. This review will provide researchers with comprehensive information and cautions needed to study adipose tissues in mouse models.

The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.

Computational tools are commonly used in untargeted metabolomics to automatically extract metabolic features from liquid chromatography-mass spectrometry (LC-MS) raw data. However, due to the incapability of software to accurately determine chromatographic peak heights/areas for features with poor chromatographic peak shape, automated data processing in untargeted metabolomics faces additional quantitative variation (i.e., computational variation) besides the well-recognized analytical and biological variations. In this work, using multiple biological samples, we investigated how experimental factors, including sample concentrations, LC separation columns, and data processing programs, contribute to computational variation. For example, we found that the peak height (PH)-based quantification is more precise when MS-DIAL was used for data processing. We further systematically compared the different patterns of computational variation between PH- and peak area (PA)-based quantitative measurements. Our results suggest that the magnitude of computational variation is highly consistent at a given concentration. Hence, we proposed a quality control (QC) sample-based correction workflow to minimize computational variation by automatically selecting PH or PA-based measurement for each intensity value. This bioinformatic solution was demonstrated in a metabolomic comparison of leukemia patients before and after chemotherapy. Our novel workflow can be effectively applied on 652 out of 915 metabolic features, and over 31% (206 out of 652) of corrected features showed distinctly changed statistical significance. Overall, this work highlights computational variation, a considerable but underinvestigated quantitative variability in omics-scale quantitative analyses. In addition, the proposed bioinformatic solution can minimize computational variation, thus providing a more confident statistical comparison among biological groups in quantitative metabolomics.

Skeletal muscle function is inferred from the spatial arrangement of muscle fiber architecture, which corresponds to myofiber molecular and metabolic features. Myofiber features are often determined using immunofluorescence on a local sampling, typically obtained from a median region. This median region is assumed to represent the entire muscle. However, it remains largely unknown to what extent this local sampling represents the entire muscle. We present a pipeline to study the architecture of muscle fiber features over the entire muscle, including sectioning, staining, imaging to image quantification and data-driven analysis with Myofiber type were identified by the expression of myosin heavy chain (MyHC) isoforms, representing contraction properties. We reconstructed muscle architecture from consecutive cross-sections stained for laminin and MyHC isoforms. Examining the entire muscle using consecutive cross-sections is extremely laborious, we provide consideration to reduce the dataset without loosing spatial information. Data-driven analysis with over 150,000 myofibers showed spatial variations in myofiber geometric features, myofiber type, and the distribution of neuromuscular junctions over the entire muscle. We present a workflow to study histological changes over the entire muscle using high-throughput imaging, image quantification, and data-driven analysis. Our results suggest that asymmetric spatial distribution of these features over the entire muscle could impact muscle function. Therefore, instead of a single sampling from a median region, representative regions covering the entire muscle should be investigated in future studies.

Tumour recurrence is a serious impediment to cancer treatment, but the mechanisms involved are poorly understood. The most frequently used anti-tumour therapies—chemotherapy and radiotherapy—target highly proliferative cancer cells. However non- or slow-proliferative dormant cancer cells can persist after treatment, eventually causing tumour relapse. Whereas the reversible growth arrest mechanism allows quiescent cells to re-enter the cell cycle, senescent cells are largely thought to be irreversibly arrested, and may instead contribute to tumour growth and relapse through paracrine signalling mechanisms. Thus, due to the differences in their growth arrest mechanism, metabolic features, plasticity and adaptation to their respective tumour microenvironment, dormant-senescent and -quiescent cancer cells could have different but complementary roles in fuelling tumour growth. In this review article, we discuss the implication of dormant cancer cells in tumour relapse and the need to understand how quiescent and senescent cells, respectively, may play a part in this process., In this review article, Karla Santos-de-Frutos and Nabil Djouder discuss the implication of dormant cancer cells in tumour relapse and the roles quiescent and senescent cells may play in this process.

Coral reefs globally are increasingly impacted by climate change. High temperature and pCO2 levels disrupt multiple physiological and biochemical pathways in marine organisms, often leading to disease and mortality in sensitive reef species. Host-associated microbes contribute critical functions that underpin host health, and environmentally induced changes in microbial communities represent a potential source for new metabolic features within holobiont systems. However, whether the acquisition of new beneficial microbial functions contributes to environmental acclimatisation of reef species is currently unknown. Using extensively studied model systems, we identify potential direct and indirect microbiome-mediated mechanisms that may contribute to environmental acclimatisation in reef invertebrate species. These mechanisms include increasing energy metabolism in the host, reduction of oxidative stress, regulation of nutrients in host cells, and increased pathogen resistance. We also propose a robust experimental strategy to test how microbial metabolic pathways may facilitate environmental acclimatisation of reef taxa. Understanding the mechanisms of microbiome-mediated acclimatisation and the timescales over which it can occur will be critical for predicting reef ecosystem dynamics under future climate scenarios and applying effective reef conservation strategies.

Recent studies have identified great similarities and interferences between the epithelial layers of the digestive tract, the airways and the cutaneous layer. The relationship between these structures seems to implicate signaling pathways, cellular components and metabolic features, and has led to the definition of a gut-lung-skin barrier. Inflammation seems to involve common features in these tissues; therefore, analyzing the similarities and differences in the modulation of its biomarkers can yield significant data promoting a better understanding of the particularities of specific signaling pathways and cellular effects. Cannabinoids are well known for a wide array of beneficial effects, including anti-inflammatory properties. This paper aims to explore the effects of natural and synthetic cannabinoids, including the components of the endocannabinoid system, in relation to the inflammation of the gut-lung-skin barrier epithelia. Recent advancements in the use of cannabinoids as anti-inflammatory substances in various disorders of the gut, lungs and skin are detailed. Some studies have reported mixed or controversial results, and these have also been addressed in our paper.

We present the annotated draft genome sequences of five fungal strains isolated from kefir grains. These isolates included three ascomycetous ( Candida californica , Kazachstania exigua , and Kazachstania unispora ) and one basidiomycetous ( Rhodotorula mucilaginosa ) species. The results revealed a detailed overview of the metabolic features of kefir fungi that will be potentially useful in biotechnological applications.

Human sexuality is a complex reality, including gender identity and sexual orientation. A widespread approach to study human sexuality is to compare groups with opposite sexual approaches such as cisgenders vs transgenders and heterosexuals vs homosexuals. Neuroimaging studies have found brain differences between these groups of individuals. Nevertheless, they reported conflicting results and limitations such as small samples’ sizes and the considerable overlap between such groups makes it difficult to draw accurate conclusions. This systematic review explored structural, functional and metabolic features of the ‘cisgender brain’ compared with the ‘transgender brain’ before hormonal treatment and the ‘heterosexual brain’ compared to the ‘homosexual brain’ from the analysis of the neuroimaging literature up to 2018. Our main aim is to help identifying biological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. Our results suggest that the majority of neuroanatomical, neurophysiological, and neurometabolic features in transgender individuals resemble those of their natal sex rather than those of their experienced gender and in homosexual individuals these resemble those of their same sex heterosexual population rather than their opposite sex heterosexual population. However, it is always difficult to interpret null findings with non-invasive neuroimaging. Given the gross nature of these measures, it is still possible that there are differences that are too subtle to measure with available tools yet have the impact of contributing to gender identity and sexual orientation. Moreover, conflicting results, also contributed to the impossibility of identifying specific brain features which consistently differ between cis- and transgender nor between hetero- and homosexual groups. The small number of studies, the small sample size of each study, and the heterogeneity of the investigations made impossible to meta-analyse all the data extracted. Further studies are necessary to increase the understanding of the neurological substrate of human sexuality.

Mortierella alpina is an oleaginous filamentous fungus with considerable lipid productivity, and it has been widely used for industrial production of arachidonic acid. The fermentation process of M. alpina is complicated and can be affected by various factors; therefore, a comprehensive knowledge of its metabolic characteristics and key factors governing lipid biosynthesis is required to further improve its industrial performance. In this review, we discuss the metabolic features and extracellular factors that affect lipid biosynthesis in M. alpina. The current progress in fermentation optimisation and metabolic engineering to improve lipid yield are also summarised. Moreover, we review the applications of M. alpina in the food industry and propose fermentation strategies for better utilisation of this genus in the future. In our opinion, the economic performance of M. alpina should be enhanced from multiple levels, including strains with ideal traits, efficient fermentation strategies, controllable fermentation costs, and competitive products of both high value and productivity. By reviewing the peculiarities of M. alpina and current progress to improve its suitability for biotechnological production, we wish to provide more efficient strategies for future development of M. alpina as a high-value lipid cell factory. KEY POINTS: • Understanding M. alpina metabolism is helpful for rational design of its fermentation processes. • Nitrogen source is a key point that affects PUFA's component and fermentation cost in M. alpina. • Dynamic fermentation strategy combined with breeding is needed to increase lipid yield in M. alpina.

Background Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. Methods Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case–control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored. Results Twenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. l-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis. Conclusions Distinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. l-arginine and kynurenine were correlated with the severity of silicosis.

With continuously increased scan rate and sensitivity, high resolution mass spectrometry (HRMS) allows for both reliable targeted analysis (e.g., parallel reaction monitoring, PRM) and a global overview for discovery-based untargeted profiling (e.g., data dependent acquisition, DDA) to be performed. Based on previous study on PRM for large scale targeted metabolomics quantification, we developed an innovative method merged targeted and untargeted approaches in a single run. In our workflow, the scheduled PRM for targeted analysis of amino acids and derivatives combined with the full scan was acquired in every sample injection by hydrophilic interaction liquid chromatography tandem quadrupole-Orbitrap high resolution mass spectrometry (HILIC-Q-Orbitrap HRMS). The identification of metabolic features from full scan was further performed with DDA methodology on grouped quality control (QC) samples and matched with available database. Specifically, 20 amino acids and 40 derivatives were selected for targeted analysis with optimal chromatographic separation and PRM parameters. All isomers within the selected metabolites were totally separated in the robust HILIC condition. 36 of selected metabolites were well-detected and showed a good linearity and reproducibility in NIST SRM 1950 plasma. Moreover, the absolute quantification performance of targeted PRM method was systematically validated using 10 amino acids with the corresponding stable isotope-labeled internal standards (SIL-IS). Finally, the newly developed method was successfully applied to analysis of the plasma samples from patients of pancreatic benign tumor and pancreatic cancer. The significant reduction of circulating amino acids in patients with pancreatic malignancy was confirmed by targeted PRM method and other amino acids modifications as well as polar metabolites were identified with untargeted profiling. Therefore, we have established a workflow that combines specifically and reliably targeted PRM method as well as broad-coverage untargeted profiling, which provides an innovative strategy for basic and clinical metabolomics study.

Hair is a unique biological matrix that adsorbs short-term exposures (e. g., environmental contaminants and personal care products) on its surface and also embeds endogenous metabolites and long-term exposures in its matrix. In this work, we developed an untargeted metabolomics workflow to profile both temporal exposure chemicals and endogenous metabolites in the same hair sample. This analytical workflow begins with the extraction of short-term exposures from hair surfaces through washing. Further development of mechanical homogenization extracts endogenous metabolites and long-term exposures from the cleaned hair. Both solutions of hair wash and hair extract were analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics for global-scale metabolic profiling. After analysis, raw data were processed using bioinformatic programs recently developed specifically for exposome research. Using optimized experimental conditions, we detected a total of 10,005 and 9,584 metabolic features from hair wash and extraction samples, respectively. Among them, 274 and 276 features can be definitively confirmed by MS2 spectral matching against spectral library, and an additional 3,356 and 3,079 features were tentatively confirmed as biotransformation metabolites. To demonstrate the performance of our hair metabolomics, we collected hair samples from three female volunteers and tested their hair metabolic changes before and after a 2-day exposure exercise. Our results show that 645 features from wash and 89 features from extract were significantly changed from the 2-day exposure. Altogether, this work provides a novel analytical approach to study the hair metabolome and exposome at a global scale, which can be implemented in a wide range of biological applications for a deeper understanding of the impact of environmental and genetic factors on human health.

Adipose tissue is composed of adipocytes and cells from the stromal vascular fraction. In this issue of Cell Metabolism, Backdahl et al. (2021) use spatial transcriptomics to provide a first glimpse at the architecture of human adipose tissue. The authors identify distinct adipocyte subpopulations with specific metabolic features.

Coronavirus disease 2019 (COVID-19) represents a significant threat to global well-being and safety. Controlling it and reducing the rate of death as soon as possible is a pressing job for the healthcare sector. The possible therapeutic agents used in COVID-19 are from the past encounters in combating SARS, MERS, and other viruses. Assuming that broad-spectrum antiviral drugs have long been accepted on the market to treat various infectious diseases, their metabolic features, dosage, possible efficacy, and side effects are yet to be studied for the current scenario. Repurposing of clinically approved drugs may be a salient short-term approach for the treatment of novel coronavirus. But the downside is that these therapies are too “broad spectrum” to target COVID-19 directly. Therefore, its side effects cannot be underrated. A number of clinical trials are underway to evaluate the effectiveness of other treatment options.

Despite the many recent breakthroughs in cancer research, oncology has traditionally been seen as a distinct field from other diseases. Recently, more attention has been paid to repurposing established therapeutic strategies and targets of other diseases towards cancer treatment, with some of these attempts generating promising outcomes [1, 2]. Recent studies using advanced metabolomics technologies [3] have shown evidence of close metabolic similarities between cancer and neurological diseases. These studies have unveiled several metabolic characteristics shared by these two categories of diseases, including metabolism of glutamine, gamma-aminobutyric acid (GABA), and N-acetyl-aspartyl-glutamate (NAAG) [4–6]. The striking metabolic overlap between cancer and neurological diseases sheds light on novel therapeutic strategies for cancer treatment. For example, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), one of the glutamate carboxypeptidase II (GCP II) inhibitors that prevent the conversion of NAAG to glutamate, has been shown to suppress cancer growth [6, 7]. These promising results have led to an increased interest in integrating this metabolic overlap between cancer and neurological diseases into the study of cancer metabolism. The advantages of studying this metabolic overlap include not only drug repurposing but also translating existing knowledge from neurological diseases to the field of cancer research. This chapter discusses the specific overlapping metabolic features between cancer and neurological diseases, focusing on glutamine, GABA, and NAAG metabolisms. Understanding the interconnections between cancer and neurological diseases will guide researchers and clinicians to find more effective cancer treatments.

Gut microbial dysbiosis and altered metabonomics have been implicated in the pathogenesis of Crohn’s disease (CD). The aim of our study was to characterize the gut microbiome structure and metabolic activities in pediatric CD patients with different clinical outcomes after infliximab (IFX) therapy. Fecal samples were collected from 20 healthy children and 29 newly diagnosed pediatric CD patients. 16S rRNA/ITS2 gene sequencing and targeted metabolomics analysis were applied to profile the gut bacterial microbiome, mycobiome, and metabolome, respectively. Pediatric CD patients exhibited lower relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Faecalibacterium, Clostridium clusters IV and XIVb, Roseburia, and Ruminococcus, which were correlated with reduced fecal levels of SCFAs. Decreased unconjugated bile acids (BAs) pool size and a lower unconjugated/conjugated BAs ratio were associated with reduced relative abundances of Bifidobacterium and Clostridium clusters IV and XIVb which contain bile salt hydrolases (BSH) genes. IFX treatment enriched the BSH-producing bacteria in CD subjects, which may explain a decreased level of conjugated BAs and an increase in unconjugated BAs as well as the unconjugated/conjugated BAs ratio. Furthermore, a sustained response (SR) of IFX therapy was associated with higher abundances of Methylobacterium, Sphingomonas, Staphylococcus, and Streptococcus, and higher fecal concentrations of amino acids, including L-aspartic acid, linoleic acid, and L-lactic acid at baseline. Our study suggests that the effects of IFX might be partially mediated by enriching bacteria taxa that producing SCFAs and BSH thereby inhibiting inflammation and restoring the BA metabolism. Some fecal bacteria and metabolites may be predictive of outcomes of IFX therapy for pediatric CD patients.

Objective The aim of this study was to investigate the diagnostic accuracy of staging 18 F-FDG-PET/CT in laryngeal cancer, compare these results with conventional imaging (CI) and assess the value of 18 F-FDG-PET/CT features to predict survival. Methods Fifty-four patients with laryngeal squamous cell cancer and baseline 18 F-FDG-PET/CT were retrospectively enrolled. The PET images were analyzed visually and semi-quantitatively by measuring several metabolic parameters. A combination of clinical follow-up/imaging follow-up and/or histopathology was taken as reference standard. Progression free survival (PFS) and disease specific survival (DSS) were computed using Kaplan-Meier curves. Results All primary tumors were clearly identified by CI, and 52/54 by 18 F-FDG-PET/CT with a sensitivity of 96.3%. Cervical nodal metastases were detected in 40/54 patients at 18 F-FDG-PET/CT and in 34/49 patients at CI. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy on a patient-based analysis for nodal disease were 100%, 85.7%, 94.6%, 100% and 95.9% at 18 F-FDG-PET/CT, and 91.4%, 85.7%, 94.1%, 80%, 89.8% at CI. Diagnostic performances of PET/CT and CI were not significantly different on a patient-based, side-by-side and level-by-level analysis. 18 F-FDG-PET/CT recognized distant metastases in 7 patients allowing to an upstaging. At a median follow-up of 27 months, relapse/progression of disease occurred in 31 patients and death occurred in 32. Metabolic tumor volume (MTV T), MTV total and total lesion glycolysis (TLG) showed to be independent prognostic factors for PFS. Conclusions Both CI and PET/CT had good diagnostic performances for the staging of laryngeal cancer; baseline metabolic features (MTV and TLG) showed an important prognostic value in assessing the rate of PFS.

Extremophiles are microorganisms that populate habitats considered inhospitable from an anthropocentric point of view and are able to tolerate harsh conditions such as high temperatures, extreme pHs, high concentrations of salts, toxic organic substances, and/or heavy metals. These microorganisms have been broadly studied in the last 30 years and represent precious sources of biomolecules and bioprocesses for many biotechnological applications; in this context, scientific efforts have been focused on the employment of extremophilic microbes and their metabolic pathways to develop biomonitoring and bioremediation strategies to face environmental pollution, as well as to improve biorefineries for the conversion of biomasses into various chemical compounds. This review gives an overview on the peculiar metabolic features of certain extremophilic microorganisms, with a main focus on thermophiles, which make them attractive for biotechnological applications in the field of environmental remediation; moreover, it sheds light on updated genetic systems (also those based on the CRISPR-Cas tool), which expand the potentialities of these microorganisms to be genetically manipulated for various biotechnological purposes.

In contrast to most Indigenous people in Canada, Inuit appeared until recently to have been protected from type 2 diabetes (T2D) related to obesity. We assessed the associations of metabolites (amino acids, acylcarnitines) with adiposity and biomarkers of T2D in school-aged Inuit children of Nunavik (Canada). Concentrations of metabolite were measured in plasma samples from a cross-sectional analysis of 248 children (mean age = 10.8 years). We assessed associations of plasma metabolites with adiposity measures (BMI, skinfold thicknesses) and T2D markers (insulin, glucose, adiponectin). Plasma concentrations of valine and tyrosine were higher in obese and overweight children compared to those of normal weight children (P

This protocol describes the extraction and analysis of bacterial metabolites to determine the metabolic changes pertaining to their responses to different types of antibiotics. Polar metabolites are extracted using a methanol-based extraction. Sensitive, specific, and semi-quantitative metabolite analysis was performed using a high-performance liquid chromatography coupled to a high-resolution quadrupole-Orbitrap mass spectrometry. Using our example bacteria as a demonstration, 14,528 metabolic features can be detected, and 1448 metabolites were putatively identified via basic database search. Additionally, 93 metabolites can be confidently identified via high-purity standards. Statistical analysis of these metabolites can pinpoint crucial changes in metabolic states of pathogens going through antibiotic treatment, which may assist our understanding of the antibiotic mechanism of actions from a metabolic perspective.

Rapid screening of infected people plays a crucial role in interrupting infection chains. However, the current methods for identification of bacteria are very tedious and labor intense. Fast on-site screening for pathogens based on volatile organic compounds (VOCs) by ion mobility spectrometry (IMS) could help to differentiate between healthy and potentially infected subjects. As a first step towards this, the feasibility of differentiating between seven different bacteria including resistant strains was assessed using IMS coupled to multicapillary columns (MCC-IMS). The headspace above bacterial cultures was directly drawn and analyzed by MCC-IMS after 90 min of incubation. A cluster analysis software and statistical methods were applied to select discriminative VOC clusters. As a result, 63 VOC clusters were identified, enabling the differentiation between all investigated bacterial strains using canonical discriminant analysis. These 63 clusters were reduced to 7 discriminative VOC clusters by constructing a hierarchical classification tree. Using this tree, all bacteria including resistant strains could be classified with an AUC of 1.0 by receiver-operating characteristic analysis. In conclusion, MCC-IMS is able to differentiate the tested bacterial species, even the non-resistant and their corresponding resistant strains, based on VOC patterns after 90 min of cultivation. Although this result is very promising, in vivo studies need to be performed to investigate if this technology is able to also classify clinical samples. With a short analysis time of 5 min, MCC-IMS is quite attractive for a rapid screening for possible infections in various locations from hospitals to airports.Key Points• Differentiation of bacteria by MCC-IMS is shown after 90-min cultivation.• Non-resistant and resistant strains can be distinguished.• Classification of bacteria is possible based on metabolic features.

Recurrent major depressive disorder (rMDD) is a relapsing-remitting disease with high morbidity and a 5-year risk of recurrence of up to 80%. This was a prospective pilot study to examine the potential diagnostic and prognostic value of targeted plasma metabolomics in the care of patients with rMDD in remission. We used an established LC-MS/MS platform to measure 399 metabolites in 68 subjects with rMDD (n = 45 females and 23 males) in antidepressant-free remission and 59 age- and sex-matched controls (n = 40 females and 19 males). Patients were then followed prospectively for 2.5 years. Metabolomics explained up to 43% of the phenotypic variance. The strongest biomarkers were gender specific. 80% of the metabolic predictors of recurrence in both males and females belonged to 6 pathways: (1) phospholipids, (2) sphingomyelins, (3) glycosphingolipids, (4) eicosanoids, (5) microbiome, and (6) purines. These changes traced to altered mitochondrial regulation of cellular redox, signaling, energy, and lipid metabolism. Metabolomics identified a chemical endophenotype that could be used to stratify rrMDD patients at greatest risk for recurrence with an accuracy over 0.90 (95%CI = 0.69–1.0). Power calculations suggest that a validation study of at least 198 females and 198 males (99 cases and 99 controls each) will be needed to confirm these results. Although a small study, these results are the first to show the potential utility of metabolomics in assisting with the important clinical challenge of prospectively identifying the patients at greatest risk of recurrence of a depressive episode and those who are at lower risk.

International audience; Listeria monocytogenes is a deadly foodborne pathogen. It is ubiquitous in nature and can be found in the wilderness, in the farm environment, in the food production environment and in food products. Transmission routes are complex and progress from natural environments to contamination of foods and subsequently host infection. The ability of L. monocytogenes to persist in such a large array of habitats relies on gene expression regulation and metabolic features. When contaminated food is consumed, the fate of L. monocytogenes depends on a complex interplay between the composition of the food matrix, host susceptibility as well as strain phylogeny. Indeed, genetic features underlie fitness differences between isolates during the saprophytic lifestyle and during infection.

Lifestyle, mainly dietary, interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. We combined a hyperandrogenized PCOS mouse model with a systematic macronutrient approach, to elucidate the impact of dietary macronutrients on the development of PCOS. We identify that an optimum dietary macronutrient balance of a low protein, medium carbohydrate and fat diet can ameliorate key PCOS reproductive traits. However, PCOS mice display a hindered ability for their metabolic system to respond to diet variations, and varying macronutrient balance did not have a beneficial effect on the development of metabolic PCOS traits. We reveal that PCOS traits in a hyperandrogenic PCOS mouse model are ameliorated selectively by diet, with reproductive traits displaying greater sensitivity than metabolic traits to dietary macronutrient balance. Hence, providing evidence to support the development of evidence-based dietary interventions as a promising strategy for the treatment of PCOS, especially reproductive traits., Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. Here the authors identify an optimum dietary macronutrient balance that can rectify PCOS reproductive traits in a mouse model of PCOS, while metabolic features were less sensitive to diet changes.

Lung cancer is the leading cause of death from cancer worldwide. Recent studies demonstrated that the tumour microenvironment (TME) is pivotal for tumour progression, providing multiple targeting opportunities for therapeutic strategies. As one of the most abundant stromal cell types in the TME, tumour-associated macrophages (TAMs) exhibit high plasticity. Malignant cells alter their metabolic profiles to adapt to the limited availability of oxygen and nutrients in the TME, resulting in functional alteration of TAMs. The metabolic features of TAMs are strongly associated with their functional plasticity, which further impacts metabolic profiling in the TME and contributes to tumourigenesis and progression. Here, we review the functional determination of the TME by TAM metabolic alterations, including glycolysis as well as fatty acid and amino acid metabolism, which in turn are influenced by environmental changes. Additionally, we discuss metabolic reprogramming of TAMs to a tumouricidal phenotype as a potential antitumoural therapeutic strategy.

The objective: decline of frequency of relapses of hyperplastic processes of endometrium for the women of genesial age with surplus mass of body on the basis of improvement and introduction of algorithm of treatment-and-prophylactis and prognostic measures.Materials and methods. The conducted researches carried stage-by-stage character. So, on I stage the analysis of clinical-anamnestic, hormonal and metabolic features of patients of genesial age with surplus mass of body and hyperplastic processes of endometrium is a 1 group (n=90), patients with surplus mass of body, but without the hyperplastic processes of endometrium – 2 group (n=60).On II stage progressive, randomized, opened, comparative research of efficiency of hormonotherapy of hyperplastic processes of endometrium was conducted in 90 women of genesial age with surplus mass of body (1 group) by the agonist of gonadotropin-releasing hormone (sub-group of 1.1, n=30), progestine (sub-group of 1.2, n=30), by estrogen-gestagenic preparation (sub-group of 1.3, n=30) and means that it is powerful enough. On III stage were found out the factors of risk of uneffectiveness of treatment and recurrent flow of hyperplastic processes of endometrium for the women of genesial age with obesity. Method of incremental discriminant analysis (n=90): patients with recurrent motion of hyperplastic processes of endometrium (3 group of, n=40), patients without the relapse of hyperplastic processes of endometrium (4 group of, n=50).Results. At the comparative estimation of efficiency of treatment of hyperplastic processes of endometrium for women it was set with surplus mass of body, that frequency of relapses in 24 months takes place for 6,7% patients after therapy of а-GRG, at 46,7% patients which got norethisterone, and for 63,3% women, treated the combined oral contraceptives. A level of the forced operative treatment (hysterectomia) is 3,3% for women which got а-GRG and 23,3%, – norethisterone and combined oral contraceptives.Conclusion. For the women of genesial age with the hyperplastic processes of endometrium and surplus mass of body for treatment most effective and safe in relation to operating there is application of а-GRG on metabolic processes and hormonal status. The use of norethisterone and combined oral contraceptives is possibly in default of found out the factors of risk., Цель исследования: снижение частоты рецидивов гиперпластических процессов эндометрия у женщин репродуктивного возраста с избыточной массой тела на основе усовершенствования и внедрения алгоритма лечебно-профилактических и прогностических мероприятий.Материалы и методы. Проведенные исследования носили поэтапный характер. Так, на І этапе был проведен анализ клинико-анамнестических, гормональных и метаболических особенностей пациенток репродуктивного возраста с избыточной массой тела и гиперпластическими процессами эндометрия – 1-я группа (n=90), пациентки с избыточной массой тела, но без гиперпластических процессов эндометрия вошли во 2-ю группу (n=60).На ІІ этапе было проведено прогрессивное рандомизированное открытое сравнительное исследование эффективности гормональной терапии гиперпластических процессов эндометрия у 90 женщин репродуктивного возраста с избыточной массой тела (1-я группа) агонистом гонадотропин-рилизинг-гормона (подгруппа 1.1, n=30), прогестином (подгруппа 1.2, n=30), эстроген-гестагенным препаратом (подгруппа 1.3, n=30).На ІІІ этапе были обнаружены факторы риска неэффективности лечения и рецидивного течения гиперпластических процессов эндометрия у женщин репродуктивного возраста с ожирением. Метод пошагового дискриминантного анализа (n=90): пациентки с рецидивирующим ходом гиперпластических процессов эндометрия (3-я группа, n=40), пациентки без рецидива гиперпластических процессов эндометрия (4-я группа, n=50).Результаты. При сравнительной оценке эффективности лечения гиперпластических процессов эндометрия у женщин с избыточной массой тела было установлено, что частота рецидивов через 24 мес отмечается у 6,7% пациенток после терапии а-GRG, у 46,7% больных, которые получали норэтистерон, и у 63,3% женщин, пролеченных комбинированными оральными контрацептивами. Уровень вынужденного оперативного лечения (гистерэктомия) составляет 3,3% у женщин, которые получали а-GRG и 23,3% – у пациенток, которые принимали норэтистерон и комбинированные оральные контрацептивы.Заключение. У женщин репродуктивного возраста с гиперпластическими процессами эндометрия и избыточной массой тела для лечения наиболее эффективным и безопасным относительно действия на метаболические процессы и гормональный статус является применение а-GRG. Использование норэтистерона и комбинированных оральных контрацептивов возможно при отсутствии обнаруженных факторов риска., Мета дослідження: зниження частоти рецидивів гіперпластичних процесів ендометрія у жінок репродуктивного віку з надмірною масою тіла на основі удосконалення та впровадження алгоритму лікувально-профілактичних та прогностичних заходів.Матеріали та методи. Проведені дослідження носили поетапний характер. Так, на І етапі було проведено аналіз клініко-анамнестичних, гормональних і метаболічних особливостей пацієнток репродуктивного віку з надмірною масою тіла та гіперпластичними процесами ендометрія – 1-а група (n=90), пацієнтки з надмірною масою тіла, але без гіперпластичних процесів ендометрія включено до 2-ї групи (n=60).На ІІ етапі було проведено прогресивне рандомізоване відкрите порівняльне дослідження ефективності гормональної терапії гіпер-пластичних процесів ендометрія у 90 жінок репродуктивного віку з надмірною масою тіла (1-а група) агоністом гонадотропін-рилізинг-гормону (підгрупа 1.1, n=30), прогестином (підгрупа 1.2, n=30), естроген-гестагенним препаратом (підгрупа 1.3, n=30).На ІІІ етапі було виявлено фактори ризику неефективності лікування і рецидивного перебігу гіперпластичних процесів ендометрія у жінок репродуктивного віку з ожирінням. Метод покрокового дискримінантного аналізу (n=90): пацієнтки з рецидивуючим перебігом гіперпластичних процесів ендометрія (3-я група, n=40), пацієнтки без рецидиву гіперпластичних процесів ендометрія (4-а група, n=50).Результати. Під час порівняльного оцінювання ефективності лікування гіперпластичних процесів ендометрія у жінок із надмірною масою тіла було встановлено, що частота рецидивів через 24 міс спостерігається у 6,7% пацієнток після терапії a-GRG, у 46,7% хворих, що отримували норетистерон, у 63,3% жінок, що вживала комбіновані оральні контрацептиви. Рівень вимушеного оперативного лікування (гістеректомія) становить 3,3% у жінок, які отримували a-GRG та 23,3% – у жінок, які вживали норетистерон та комбіновані оральні контрацептиви.Заключення. У жінок репродуктивного віку з гіперпластичними процесами ендометрія та надмірною масою тіла для лікування найбільш ефективним і безпечним щодо дії на метаболічні процеси і гормональний статус є застосування a-GRG. Використання норетистерону і комбінованих оральних контрацептивів можливо за відсутності виявлених чинників ризику.

BackgroundCervical dystonia is the most common of the adult-onset focal dystonias. Most cases are idiopathic. The current view is that cervical dystonia may be caused by some combination of genetic and environmental factors. Genetic contributions have been studied extensively, but there are few studies of other factors.ObjectiveTo conduct an exploratory metabolomics analysis of cervical dystonia to identify potentially abnormal metabolites or altered biological pathways.MethodsPlasma samples from 100 cases with idiopathic cervical dystonia and 100 controls were compared using liquid chromatography coupled with mass spectrometry-based metabolomics.ResultsA total of 7,346 metabolic features remained after quality control, and 289 demonstrated significant differences between cases and controls, depending on statistical criteria chosen. Pathway analysis revealed 9 biological processes to be significantly associated at pConclusionThis is the first large scale metabolomics study for any type of dystonia. The results may provide potential novel insights into the biology of cervical dystonia.