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Microscale-based separations are increasingly being applied in the field of metabolomics for the analysis of small-molecule metabolites. These methods have the potential to provide improved sensitivity, less solvent waste, and reduced sample-size requirements. Ion-pair free microflow-based global metabolomics methods, which we recently reported, were further compared to analytical flow ion-pairing reagent containing methods using a sample set from a urea cycle disorder (UCD) mouse model. Mouse urine and brain homogenate samples representing healthy, diseased, and disease-treated animals were analyzed by both methods. Data processing was performed using univariate and multivariate techniques followed by analyte trend analysis. The microflow methods performed comparably to the analytical flow ion-pairing methods with the ability to separate the three sample groups when analyzed by partial least-squares analysis. The number of detected metabolic features present after each data processing step was similar between the microflow-based methods and the ion-pairing methods in the negative ionization mode. The observed analyte trend and coverage of known UCD biomarkers were the same for both evaluated approaches. The 12.5-fold reduction in sample injection volume required for the microflow-based separations highlights the potential of this method to support studies with sample-size limitations.

Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.

Background: The main components of mineral metabolism can influence non-classical target organs such as adipose tissue, pancreas, vascular wall. The «metabolic» effects of parathyroid hormone (PTH) and other participants of phosphorus-calcium metabolism in the hyperfunction of parathyroid glands remain unclear. The study of disorders of carbohydrate, fat and other types of metabolism in primary hyperparathyroidism (PHPT) will help to develop effective measures for prophylaxis and treatment of the patients in order to improve the quality and life span of the population.Aim: To study the main parameters of metabolism in young patients with an active stage of PHPT before surgical treatment.Materials and methods: A one-stage comparative study of young patients with PHPT and healthy volunteers matched by sex, age and body mass index (BMI) was carried out. The participants underwent a comprehensive biochemical and hormonal examination, a hyperinsulinemic euglycemic clamp and a bioimpedance analysis of the body composition.Results: 21 patients with PHPT and 18 healthy volunteers were included in the study. Patients with PHPT have higher level of serum triglycerides (p=0.003) without statistically differences of the main carbohydrate and purine parameters comparing with the control group. Visceral obesity were revealed in 42.9% of patients, including those with a normal BMI. Insulin resistance in the PHPT group was noted in 52.4% of cases, while the M-index was statistically lower than in the control subgroup (p=0.008), despite of the comparable body composition of the participants. The M-index showed a positive correlation with blood phosphorus level (p=0.010) only in the general group. Statistically positive correlations of PTH, albumin-corrected calcium and osteocalcin with triglyceride levels, calcium with fasting glycaemia, and PTH with uric acid levels were determined.Conclusion: PHPT is associated with insulin resistance in patients that is the main risk factor for the development of serious carbohydrate and fat disorders. The positive correlation of PTH and blood calcium levels with triglycerides, as well as the tendency to hypertriglyceridemia comparing with healthy volunteers, suggest the disease effect on the development of dyslipidemia.

BACKGROUND AND PURPOSE To compare and characterize metabolic features of high- and low-grade glioma tumors using 68 Ga-PSMA-617 and 18 F-FDG positron emission tomography/computed tomography (PET/CT). METHODS Thirty patients who underwent both 68 Ga-PSMA-617 and 18 F-FDG PET/CT over 2 consecutive days and then underwent surgical treatment were retrospectively identified. All tumors were diagnosed histologically. This report includes 16 high-grade glioma (HGG) and 14 low-grade glioma (LGG) tumors. Standard uptake value (SUV) and target to nontarget (T/NT) were quantitatively investigated through the entire tumor region. Statistical analyses were performed using area under the curve (AUC) and comparison of two means. RESULTS SUVmax and SUVmean were the most effective (AUC, 0.96 and 0.94 for PSMA PET; AUC, 0.79 and 0.74 for FDG PET, respectively) for differentiating HGGs from LGGs. These methods distinguished between HGG and LGG effectively (PSMA PET: SUVmax , 5.766 ± 3.945 vs. 0.7364 ± 0.5295, p < 0.0001; SUVmean , 1.666 ± 1.680 and 0.1514 ± 0.1534, p < 0.0001, respectively) (FDG PET: SUVmax , 11.67 ± 3.639 and 9.118 ± 6.612; SUVmean , 5.648 ± 2.114 and 4.435 ± 2.872; p = 0.0083, 0.0262, respectively). The Youden index for SUVmax and SUVmean of 68 Ga-PSMA-617 and 18 F-FDG were 0.82 and 0.79 and 0.54 and 0.61, separately. T/NTmax was helpful for visual inspection of 68 Ga-PSMA-617-PET images (T/NTmax : 1.291 ± 0.9553 in grade II, 5.25 ± 2.435 in grade III, and 13.61 ± 13.84 in grade IV). T/NTmax differed significantly between LGG and HGG and between subtypes of LGG. CONCLUSION PET/CT with 68 Ga-PSMA-617 and 18 F-FDG may help distinguish between HGG and LGG, and 68 Ga-PSMA-617 PET/CT is superior to18 F-FDG in differentiating HGG and LGG.

Acute myeloid leukemia (AML) is a cancer derived from the myeloid lineage of blood cells, characterized by overproduction of leukemic blasts. Although therapeutic improvements have made a significant impact on the outcomes of patients with AML, survival rates remain low due to a high incidence of relapse. Similar to how wildfires can reignite from hidden embers not extinguished from an initial round of firefighting, leukemic stem cells (LSCs) are the embers remaining after completion of traditional chemotherapeutic treatments. LSCs exhibit a unique metabolic profile and contain metabolically distinct subpopulations. In this review, we detail the metabolic features of LSCs and how thetse characteristics promote resistance to traditional chemotherapy. We also discuss new therapeutic approaches that target metabolic vulnerabilities of LSC to selectively eradicate them.

Purpose The aim of our work is to evaluate the correlation of two-dimensional (2D) and three-dimensional (3D) radiomics and metabolic features of hepatocellular carcinoma (HCC) with tumour diameter, staging, and metabolic tumour volume (MTV). Material and methods Thirty-three patients with HCC were studied using 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (18F [FDG] PET/CT). The tumours were segmented from the PET images after CT correction. Metabolic parameters and 35 radiomics features were compared using 2D and 3D modes. The metabolic parameters and tumour morphology were compared using 2 different types of software. Tumour heterogeneity was studied in both metabolic parameters and radiomics features. Finally, the correlation between the metabolic and radiomics features in 3D mode, as well as tumour morphology and staging according to the American Joint Committee on Cancer (AJCC) staging were studied. Results Most of the metabolic parameters and radiomics features are statically stable through the 2D and 3D modes. Most of the 3D mode features show a correlation with metabolic parameters; the total lesion glycolysis (TLG) shows the highest correlation, with a Spearman correlation coefficient (rs) of 0.9776. Also, the grey level run length matrix/run length non-uniformity (GLRLM_RLNU) from radiomics features exhibits a correlation with a Spearman correlation coefficient of 0.9733. Maximum tumour diameter is correlated with TLG and GLRLM_RLNU, with rs equal to 0.7461 and 0.7143, respectively. Regarding AJCC staging, some features show a medium but prognostic correlation. In the case of 2D-mode features, all metabolic and radiomics features show no significant correlation with MTV, AJCC staging, and tumour maximum diameter. Conclusions Most of the normal metabolic parameters and radiomics features are statistically stable through the 3D and 2D modes. 3D radiomics features are significantly correlated with tumour volume, maximum diameter, and staging. Conversely, 2D features have negligible correlation with the same parameters. Therefore, 3D mode features are preferable and can accurately evaluate tumour heterogeneity.

Introduction and Aim: PCOS is a complicated endocrinopathy of women in reproductive age with unknown etiology causing ovulatory dysfunction and metabolic disturbances. The present study investigated the effects of ethanolic seed extract of Caesalpinia bonducella (ESECB) in a mifepristone model of polycystic ovarian syndrome, which has the same clinical and metabolic features as in PCOS women. Materials and Methods: A daily administration of mifepristone (4mg/kg b.w.) to female rats for 8 days induces PCOS by indicating persistent estrous cycle. PCOS induced rats were treated with ESECB 200mg and 400mg/kg b. w. per oral for 28 days and at the end, the weight of the body and reproductive organs were determined. Biochemical parameters were also estimated. Metformin was used as a standard drug. Results: A significant increase (p

The possibility of selectively delivering metal complexes to a defined cohort of cells on the basis of their metabolic features is a highly challenging goal, which may be extremely useful for a series of purposes, including diagnosis and therapy of pathological states, such as cancer. Tumor cells display augmented requests for carbohydrates and, in particular, for glucose in order to sustain their high proliferation rate, which causes an increased glycolytic process (Warburg effect). Since several metal complexes display diagnostic and/or therapeutic properties, their conjugation to carbohydrate portions often induce their preferential accumulation in cancer cells, similarly to what is observed with fluorodeoxyglucose (FDG). In this review we have considered the latest developments of glycoconjugates containing metal complexes in their structures. These compounds are classified as diagnostic or therapeutic agents and are further systematically discussed on the basis of the metal atom they contain. Several diagnostic techniques are possible with these probes, since, depending on the metal species included in their structures, they may be employed in nuclear medicine (PET, SPECT), magnetic resonance imaging, luminescence and phosphorescence. At the same time, the lack of selective cytotoxicity displayed by several metal-based chemotherapeutic agents, may also be solved by the conjugation of these agents to carbohydrate portions. Overall, data so far available reveal the great potential of this chemical class in the early detection and in the cure of severe neoplastic diseases, which still needs to be fully explored in the clinic.

Disturbances during intrauterine life have been implicated in the origin of polycystic ovary syndrome (PCOS) and may modify the endocrine and metabolic function of a child born to a mother with PCOS independently of genetic inheritance and sex. Daughters of women with PCOS show 4 components of the syndrome (ovarian dysfunction, neuroendocrine dysfunction, hyperandrogenism, and hyperinsulinemia) that appear in a sequential pattern during infancy, childhood, and puberty increasing the chance for developing PCOS during adulthood. Sons born to mothers with PCOS show few reproductive but important metabolic disturbances. These metabolic features, both in girls and boys, have early cardiovascular effects that may put these children at risk for later cardiovascular disease. Recent combined animal/human models have been able to identify common markers that will help us elucidate the precise mechanisms involved in the transgenerational transmission of this syndrome and provide possible therapies to prevent it.

ObjectivesTo investigate metabolic features that may predispose to GCA in a nested case–control study.MethodsIndividuals who developed GCA after inclusion in a population-based health survey (the Malmö Preventive Medicine Project; N = 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database.ResultsA total of 76 cases with a confirmed incident diagnosis of GCA (61% female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0–32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (S.d. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (S.d. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (S.d. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides].ConclusionDevelopment of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA.

The effect of metabolic characteristics on the prognosis of patients with metastatic renal cell carcinoma remains controversial. We investigated the associations between metabolic features of each individual and disease prognosis in patients with metastatic renal cell carcinoma. Data of 1,584 patients with metastatic renal cell carcinoma from a multi-institutional database were retrospectively analyzed. The entire cohort was stratified into three subgroups according to how many patients had abnormal metabolic features (hypertension, diabetes mellitus, and low body mass index). The Kaplan-Meier and Cox proportional analyses were performed to investigate the associations between abnormal metabolic features and disease prognosis. mThere were 465 subjects without any metabolic features, 995 with one or two, and 124 with three. When the survival outcomes were compared according to the number of metabolic features, patients with higher numbers of metabolic features had significantly shorter overall and cancer-specific survival than those with fewer metabolic features (all p values

Background Liver involvement in Gaucher disease (GD) is a result of glucosylceramide (GL1) and its deacylated lysolipid, glucosylsphingosine (lyso-GL1) infiltration of macrophages. The long-term liver-related complications of GD could include liver fibrosis and cirrhosis. The aim of the study was to evaluate clinical utility and relevance of TE by FibroScan in GD patients by assessing two parameters: controlled attenuation parameter (CAP) and liver stiffness (LS), in regard of GD-related variables, type of GD, age of patients, enzymatic replacement therapy (ERT), and metabolic features. Methods 59 Polish patients (55 adults, 4 children) with GD (43 patients with type 1 and 16 patients with type 3) aged 7–86 years, underwent TE by FibroScan; elevated CAP was defined as >250 dB/m and elevated LS as >7 kPa. All patients, except five patients with type 1 GD (patients' refusal), were treated by ERT. Results Elevated CAP was present in 23% of GD1 patients and 19% of GD3 patients. Elevated LS was present in 21% of GD1 patients and 13% of GD3 patients. CAP was fairly, positively (ρ = 0.356) correlated with BMI. LS was fairly, positively (ρ = 0.4) correlated with patient's age, as well as the age at start of ERT (ρ = 0.326). CAP was strongly, negatively (ρ = −0.52) correlated with the age at start of ERT. LS and CAP were correlated (strongly, positively) only in GD3. Conclusions TE by FibroScan could be considered as an additional method for evaluating GD patients for non-invasive assessment of CAP and LS. The investigation of serial TE measurements in untreated as well as treated GD patients is needed to better determine whether this technology should be added to recommendations for monitoring GD patients. TE by FibroScan could be performed in GD patients with increased BMI and especially those with metabolic syndrome as they have other important risks for liver disease. After our analysis we think these risks factors are independent of GD but still very important for their overall health.

Rewiring cellular metabolism is a key hallmark of cancer. Multiple evidences show that alterations in various metabolic circuits directly contribute to the tumorigenic process at different levels (e.g. cancer initiation, metastasis, resistance). However, the characterization of the metabolic profile of Neurofibromatosis type 1 (NF1)-related neoplastic cells has been only partially elucidated both in benign neurofibromas and in malignant peripheral nerve sheath tumors (MPNSTs). Here, we illustrate the state of the art on the knowledge of the metabolic features of tumors related to NF1 and discuss their potential implications for the development of novel therapeutic perspectives.

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.

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.

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 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.

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.

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.

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

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.

Background Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. This study aimed to identify potential noninvasive metabolic biomarkers for the diagnosis and monitoring of this condition by pilot and validation analyses of patients with 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. Plasma samples were collected, and metabolomics analyses by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) were conducted. Distinct metabolic features (DMFs) among the groups 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 in the validation study 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 in the plasma of the DEW and silicosis groups, respectively, compared with the control group; these features showed the same trend in the pilot study and the validation study. 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 of plasma samples related to sphingolipid metabolism and arginine and proline metabolism were identified in the DEW and silicosis groups, respectively. L-arginine and kynurenine may have a predictive role in the diagnosis and severity of silicosis.

Ischemic stroke represents a serious medical condition which could cause survivors suffer from long-term and even lifetime disabilities. After a stroke attack, the brain would undergo varying degrees of recovery, in which the central nervous system could be reorganized spontaneously or with the help of appropriate rehabilitation. Magnetic resonance imaging (MRI) is a non-invasive technique which can provide comprehensive information on structural, functional and metabolic features of brain tissue. In the last decade, there has been an increased technical advancement in MR techniques such as voxel-based morphological analysis (VBM), diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI), arterial spin-labeled perfusion imaging (ASL), magnetic sensitivity weighted imaging (SWI), quantitative sensitivity magnetization (QSM) and magnetic resonance spectroscopy (MRS) which have been proven to be a valuable tool to study the brain tissue reorganization. Due to MRI indices of neuroplasticity related to neurological outcome could be translated to the clinic. The ultimate goal of this review is to equip readers with a fundamental understanding of advanced MR techniques and their corresponding clinical application for improving the ability to predict neuroplasticity that are most suitable for stroke management.

Head and neck cancers are the seventh most common type of cancer worldwide, with almost half of the cases affecting the oral cavity. Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. OSCC molecular pathogenesis is complex, resulting from a wide range of events that involve the interplay between genetic mutations and altered levels of transcripts, proteins, and metabolites. Metabolomics is a recently developed sub-area of omics sciences focused on the comprehensive analysis of small molecules involved in several biological pathways by high throughput technologies. This review summarizes and evaluates studies focused on the metabolomics analysis of OSCC and oral premalignant disorders to better interpret the complex process of oral carcinogenesis. Additionally, the metabolic biomarkers signatures identified so far are also included. Moreover, we discuss the limitations of these studies and make suggestions for future investigations. Although many questions about the metabolic features of OSCC have already been answered in metabolomic studies, further validation and optimization are still required to translate these findings into clinical applications.

Background and purpose: Adaptive radiation planning for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment, while traditional response evaluation criteria inefficiently characterize tumors with complex morphological features or intrinsically low metabolism. To better assess treatment response of PA, we quantify and compare regional morphological and metabolic features of the 3D pre- and post-radiation therapy (RT) tumor models. Materials and methods: Thirty-one PA patients with pre and post-RT Positron emission tomography/computed tomography (PET/CT) scans were evaluated. 3D meshes of pre- and post-RT tumors were generated and registered to establish vertex-wise correspondence. To assess tumor response, Mahalanobis distances (Mdist|Fusion) between pre- and post-RT tumor surfaces with anatomic and metabolic fused vectors were calculated for each patient. Mdist|Fusion was evaluated by overall survival (OS) prediction and survival risk classification. As a comparison, the same analyses were conducted on traditional imaging/physiological predictors, and distances measurements based on metabolic and morphological features only. Results: Among all the imaging/physiological parameters, Mdist|Fusion was shown to be the best predictor of OS (HR = 0.52, p = 0.008), while other parameters failed to reach significance. Moreover, Mdist|Fusion outperformed traditional morphologic and metabolic measurements in patient risk stratification, either alone (HR = 11.51, p

The human gastrointestinal (GI) tract contains communities of microbes (bacteria, fungi, viruses) that vary by anatomic location and impact human health. Microbial communities differ in composition based on age, diet, and location in the gastrointestinal tract. Differences in microbial composition have been associated with chronic disease states. In terms of function, microbial metabolites provide key signals that help maintain healthy human physiology. Alterations of the healthy gastrointestinal microbiome have been linked to the development of various disease states including inflammatory bowel disease, diabetes, and colorectal cancer. While the definition of a healthy GI microbiome cannot be precisely identified, features of a healthy gut microbiome include relatively greater biodiversity and relative abundances of specific phyla and genera. Microbes with desirable functional profiles for the human host have been identified, in addition to specific metabolic features of the microbiome. This article reviews the composition and function of the healthy human GI microbiome, including the relative abundances of different bacterial taxa and the specific metabolic pathways and classes of microbial metabolites contributing to human health and disease prevention.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by repeated breathing pauses during sleep, with slee disruption, intermittent hypoxia, and cardiac, metabolic and neuropsychological disturbances. Metabolic syndrome (MS) is an association of cardiovascular risk factors centered on insulin resistance.The study objective is to calculate the prevalence of MS and its components in a large group of OSAHS patients. We evaluated 350 patients addressed to The Military Hospital Iasi between 2016 and 2017 from the clinical, metabolic and polygraphic poins of view. In 235 of the 350 de patients we found OSAHS. Of the 235 patients with OSAHS, 140 (60%) meet the criteria for MS, versus 29% of the group withut OSAHS (OR = 3.608, CI = 2.1787 - 5.975). Patients with OSAHS were older, more obese, more sedentary, sleepier and presented higher cholesterol values both total cholesterol and HDL fraction, higher tryglicerides values, higher blood sugar values and blood pressure values than patients without OSAHS. The prevalence of the MS in OSAHS patients is 60%, similar to what whas reported and higher by 31% than in the non OSAHS group. Certain components and associated conditions are characteristically linked to OSAHS.

There is a critical need to improve our understanding of the pathogenesis of melanoma brain metastases (MBMs). Thus, we performed RNA-sequencing (RNA-seq) on 88 resected MBMs and 42 patient-matched extracranial metastases (ECMs); tumors with sufficient tissue also underwent whole exome sequencing, T cell receptor sequencing, and immunohistochemistry. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison to patient-matched ECMs identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-(13)C]-glucose tracing in vivo. IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPKi-resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs.

Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996–2000, n = 897), group 2 (2001–2005, n = 1,018), group 3 (2006–2010, n = 1,043), and group 4 (2011–2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period., Graphical Abstract

Objective: to study changes in the vascular endothelium state in conjunction with clinical and metabolic features in CHD patients with the concomitant nonalcoholic fatty liver disease. Methods: cross-cohort analytical study involved 86 patients, the primarily selected group consisted of 34 patients, mean age 60 (57.5; 66) with documented coronary artery disease, stable exertional angina of II-III functional class combined with NAFLD; comparison selected group: 32 patients, mean age 60.5 (51.5; 65.6) with coronary artery disease without NAFLD. The control selected group consisted of 20 healthy individuals. Results: In patients with coronary artery disease and NAFLD compared with CHD patients without NAFLD was found significantly higher levels of ADMA by 21 % (p < 0.05), CRP by 1.63 times (p < 0.05), intima-media thickness by 14.28 % (p < 0.05). Using ROC-analysis established that levels of ADMA >0.74 mmol/l is the cutting point and has an optimal ratio of sensitivity (80 %) to the specificity (82.9 %) for the diagnosis of vascular remodeling in CHD patients with concomitant NAFLD. The presence of significant direct correlation relationship of ADMA with CRP, total cholesterol, glucose, body mass index, alkaline phosphatase, ALT and significant negative relation of ADMA with HDL were found. Conclusions: In patients with coronary artery disease, combined with NAFLD structural and functional changes in vascular endothelium (increase in serum levels of ADMA, thickening of intima-media) are observed during activation of systemic inflammation (increased CRP concentration), which is associated with metabolic disorders and liver damage indicators. The value of ADMA in serum prevailing 0.74 mmol/l helps to diagnose structural and functional changes in vascular endothelium in patients with coronary artery disease, comorbid with NAFLD. coronary artery disease; nonalcoholic fatty liver disease; vascular endothelium; carotid intima-media thickness; arginine

To evaluate clinical features and metabolic disorders in men and women with non-alcoholic fatty liver disease (NAFLD).Цель исследования. Оценка особенностей клинического течения и метаболических нарушений у мужчин и женщин с неалкогольной жировой болезнью печени (НАЖБП). Материалы и методы. Обследовали 153 больных НАЖБП, из них 97 мужчин и 56 женщин. В сравнительном плане изучали клинические проявления НАЖБП. У всех пациентов НАЖБП верифицирована впервые. Исследовали функциональное состояние печени, показатели липидного, углеводного и порфиринового обмена, инсулинорезистентность (ИР). Результаты. Расстройства в функциональных показателях печени и цитолиза чаще обнаруживались у женщин. При этом достоверных различий по степени их выраженности не наблюдалось. Дисметаболизм порфиринов, расстройства в липидном обмене, гиперинсулинизм, ИР доминировали у мужчин. Более высокая гипертриглицеридемия в сочетании с ИР позволяет предположить, что сочетание этих нарушений и их бо`льшая выраженность могут способствовать формированию стеатоза печени у мужчин значительно раньше. Заключение. Основные патофизиологические и патогенетические процессы формирования НАЖБП (ИР и дислипидемия) доминируют у мужчин. Это дает основание считать мужской пол достоверным фактором риска формирования НАЖБП.

In the original articles there are data errors in some of the Figure 2 tables. The corrected Figure 2 tables follow.

Focal nodular fat sparing of the liver may show, on PET/CT imaging, prominent tracer uptake over a background of less metabolic features of steatosis. This finding, already reported with F-FDG, may mimic primary or secondary neoplasms of the liver. The authors present an additional case of nodular fat-sparing hepatic parenchyma exhibiting C-choline avidity during PET/CT assessment for biochemical recurrence of prostate cancer.

The present study examined the effectiveness of adding exercises with whole-body vibration (WBV) to aerobic training in terms of metabolic features and quality of life. Patients with non-alcoholic fatty liver disease (NAFLD), confirmed on imaging, underwent an 8-week individualized exercise program randomized between aerobic training with and without WBV. Training was performed at 60-80% heart rate workload for 165 min/week. The WBV amplitude was 2-4 mm and the training frequency was 30 Hz, for 15 min. Assessments were carried out on surrogate scores of steatosis and fibrosis including transient elastography (FibroScan), metabolic features (biochemical analysis) and quality of life (SF-36). Insulin resistance was markedly reduced ( -2.36; 95% CI: -4.96 to -0.24; P: 0.049) in aerobic training with WBV. The decrease in serum aspartate transaminase was significantly greater in aerobic training without WBV ( -14.81; 95% CI: -23.36 to -6.25; P: 0.029). There were no significant differences between groups for the other metabolic features (P< 0.05). All quality of life well-being domains improved in both groups (P< 0.05). Given this reduction in insulin resistance, WBV can usefully be added to aerobic training. However, WBV did not provide further benefits in improving metabolic properties or quality of life. La présente étude a examiné l’efficacité de l’ajout d’exercices avec vibrations globales du corps (WBV)à l’entraînement aérobie en termes de caractéristiques métaboliques et de qualité de la vie. Lespatients présentant une stéatose hépatique non alcoolique (NAFLD), confirmée en imagerie médicale et par les données cliniques, ont subi un programme d’exercice, individualisé de 8 semaines,randomisé entre un entraînement aérobie avec ou sans WBV. L’entraînement a été effectué avecune charge de travail correspondant à une fréquence cardiaque de 60 à 80 % pendant 165 min parsemaine. L”amplitude WBV était de 2 à 4 mm avec une fréquence de 30 Hz, pendant 15 min. Des évaluations ont été effectuées sur les scores de substitution de la stéatose et de la fibrose, y comprisl’élastographie transitoire (FibroScan), les caractéristiques métaboliques (analyse biochimique) et laqualité de vie (SF-36). La résistance à l’insuline a été nettement réduite (IC −2,36 : −4,96 à −0,24 ;p : 0,049) lors de l’entraînement aérobie avec le groupe WBV. La diminution des transaminases aspartiques sériques était significativement plus élevée dans l’entraînement aérobie sans WBV (IC −14,81 :−23,36 à −6,25 ; p : 0,029). Il n’y avait pas de différence entre les groupes dans les autres caractéristiquesmétaboliques (p < 0,05). Tous les domaines du « bien-être » et de la qualité de vie se sont améliorésdans les deux groupes (p < 0,05). Compte tenu de la réduction de la résistance à l’insuline, le WBV estune option additionnelle à l’entraînement aérobique. Cependant, la WBV n’a pas apporté d’avantagessupplémentaires pour améliorer les propriétés métaboliques etla qualité de la vie.

Aim: To investigate whether atrial natriuretic peptide (ANP) level is altered in polycystic ovarian syndrome (PCOS) patients with clomiphene citrate (CC) resistant and whether it correlates with insulin sensitivity markers. Methods: Serum ANP, insulin and glucose levels and the homeostasis model assessment for insulin resistance index (HOMA-IR) were evaluated among a group of PCOS women with CC resistance (n = 40). A control group (n = 30) was selected from healthy women with regular menstrual cycles. Results: Serum ANP level was significantly lower in the study group than in the control group (0.74 ± 1.1 ng/ml vs 3.17 ± 1.9 ng/ml; P

In the last decade, the field of cancer metabolism transformed itself from being a description of the metabolic features of cancer cells to become a key component of cellular transformation. Now, the potential role of this field in cancer biology is ready to be unravelled.

Teratozoospermia is one of conditions that can cause male infertility. The mechanism of teratozoospermia remains unclear. The knowledge of the metabolites in human seminal plasma (HSP) is meaningful for the pathological study of teratozoospermia. Analysis of changed metabolites in HSP can help understand the cellular mechanism, find the novel biomarkers and subsequently design a diagnosis test. In this study, the analysis of samples performed by proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) to identify the various metabolites, with the aim of finding metabolic profiles and biomarkers related to male infertility. Eighteen de-regulated metabolites were identified in fertile men compared to teratozoospermia patients. These changes illustrate the deficiencies in absorption or metabolism of these metabolites in teratozoospermia. Furthermore, metabolic profiling showed that it is not possible to classify teratozoospermia based on teratozoospermia index (TZI). To the best of our knowledge, this is the first metabolic profiling analysis of HSP described the metabolic features of teratozoospermia in a holistic view.

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p .001), 12, and 24 months of treatment (p .01). BMI showed a reduction only at 6 months (p .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p .01) and 18 months (p .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. Its pathogenesis is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of ME/CFS and diagnostic uncertainty. Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS.

Dilated Cardiomyopathy (DCM) and Chronical Degenerative Valvular Disease (CDVD) are very common in dogs nowadays. However, due to modern level in oncology we can meet chemotherapy-induced cardiomyopathies more often. We have lack of information about pathogenic mechanisms underlying Doxorubicin-induced Cardiomyopathy (DoxCM) and features differentiating it from CDVD and DCM. In this study we investigate several metabolic features of doxorubicin-induced cardiomyopathy, DCM-like phenotype cardiomyopathies and CDVD. We observed some stages of myocardium glucose metabolism in order to estimate life potential of end stage myocardium and respectively survival of patient. The study population consisted of 46 dogs of different age, sex and breed. These dogs were subgrouped due to diagnosis: Healthy dogs without heart failure, DCM, CDVD and DoxCM. Fresh myocardial biopsies taken immediately after euthanasia from left ventricular apex, freezed in liquid nitrogen for ELISA and biochemical study. Differences in metabolic profile found between of CDVD and healthy dogs were not significant. At the same time doxorubicin induced cardiomyopathy and DCM-like phenotype myocardial disease had similar changes. It should be mentioned, DCM patients had previously long history of treatment, but DoxCM group-not. Differences between DoxCM, DCM and CDVD were significant and can be explained by changes what suffering myocardium undergoes. Rapid or slow developing energy depletion leads to myocardiocytes death and heart failure. Doxorubicin-induced cardiomyopathy is far more dangerous due to rapidness of development in observed study. Myocardium, due to lack of time, had no adapting ability for acute energy depletion and massive cell death. This preliminary study shows changes induced by doxorubicin (Dox) in dogs. These findings mostly connected with mitochondrial disturbances, insulin resistance and energy depletion. In this study also shown several features connected with development of CDVD and differences from DCM.

Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue.We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset,18 years).Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016.Search terms included lipodystrophy, and age 0 to 18 years. Patients with unambiguous diagnosis of lipodystrophy were included. Lipodystrophy secondary to HIV treatment was excluded.We identified 1141 patients from 351 studies. Generalized fat loss involving face, neck, abdomen, thorax, and upper and lower limbs was explicitly reported in 65% to 93% of patients with congenital generalized lipodystrophy (CGL) and acquired generalized lipodystrophy (AGL). In familial partial lipodystrophy (FPL), fat loss occurred from upper and lower limbs, with sparing of face and neck. In acquired partial lipodystrophy (APL), upper limbs were involved while lower limbs were spared. Other features were prominent musculature, acromegaloid, acanthosis nigricans and hepatosplenomegaly. Diabetes mellitus was diagnosed in 48% (n = 222) of patients with CGL (mean age at onset, 5.3 years). Hypertriglyceridemia was observed in CGL, AGL and FPL. Multiple interventions were used, with most patients receiving ≥ 3 interventions and being ≥ 18 years of age at the initiation of interventions.To our knowledge, this is the largest reported pooled database describing lipodystrophy patients with age at onset18 years. We have suggested core and supportive clinical features and summarized data on available interventions, outcomes and mortality.