reduces the activation of macrophages in adipose tissue . The most prominent effects of IL-22 in this con- text, however, are probable those on hepatocytes that result in the increase of liver functionality. Long-term treatment with rmIL-22 decreased the hepatic expres- sion of enzymes for lipid synthesis like ATP citrate lyase (ACLY) as well as elongation of very long chain fatty acids like 6 (ELOVL6) and reduced hepatic triglyceride and cholesterol levels . Furthermore, it decreased the expression of enzymes for gluconeogenesis like glucose- 6-phosphatase and phosphoenolpyruvate carboxyki- nase (PEPCK) in hepatocytes and suppressed glucose production . Additionally, high IL-22 levels were shown to act on adipocytes and elevate the expression of genes involved in triglyceride lipolysis [e.g. hormone- sensitive lipase (LIPE) and patatin-like phospholipase domain-containing protein 2 (PNPLA2)] and fatty-acid β-oxidation (acyl-CoA oxidase 1, ACOX1) . Accord- ingly, the triglyceride content in white adipose tissue and serum was reduced in adipose mice treated with IL- 22Fc construct . High IL-22 levels seem to increase the insulin sensitivity of the liver, muscle, and adipose tissue. Accordingly, IL-22 appears to increase glucose uptake in brown adipose tissue and heat production [4, 10]. Finally, IL-22 treatment leads to reduction of constitutive serum insulin concentration in obese mice and restores insulin production in response to glu- cose provocation [4, 5, 10]. Whether the last fact is co- determinated by a direct effect of IL-22 on pancreatic beta-cells is currently controversially discussed [5, 10]. While some reports do not observe IL-22R1 expres- sion and IL-22-induced signal transduction in beta-cells , others postulated that IL-22 suppresses oxidative and endoplasmic reticulum stress in these cells and facilitates secretion of high-quality efficacious insulin . Regardless of this controversy, it remains clear, that systemic application of exogenous IL-22 is able to improve metabolic alterations in adipose mice. It is currently impossible to estimate the extent we can use these very interesting discoveries for the development of the innovative treatment of human adiposity and disturbed metabolism. Not only because experiments with hepatocytes or adipocytes from obese subjects regarding IL-22 effects are missing so far. In princi- pal, it appears quite easy to reach elevated IL-22 levels in humans: This can be achieved by application of this cytokine itself or by the activation of IL-22-inducing key signal transduction elements (e.g. aryl hydrocarbon receptor stimulation) by small molecules [as already shown for 6-formylindolo(3, 2-b)carbazole] . Further studies need to clarify whether levels of IL-22 reached in this way will be sufficient and safe. So far, at least the high caloric diet
Tamarindus indica L. (Fabaceae; common name: tam- arind) is a multipurpose tropical tree: the leaves, flowers, fruits and seeds are used to make curries, salads, stews and soups in many countries. The tender leaves of T. indica are traditionally used with lentils in Southern India, replacing the tamarind fruit. The leaves are also used to treat throat infections/coughs, fever, intestinal worm infections, uri- nary problems and liver ailments. Leaves and pulp act as a cholagogue, laxative and anticongestant and exhibit anti- oxidant activity in the liver in addition to their blood sugar- reducing properties . The leaf extracts were also shown to be antifungal and antimicrobial [23, 24]. As there are no reports concerning the utility of tamarind leaves against sodium fluoride-induced toxicity, we evaluated the efficacy of tamarind leaves in mitigating fluoride-induced metabolic alterations in carbohydrate, lipid and antioxidant profiles.
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In addition to metabolic alterations induced by the ZVp over glioblastoma cells, we have also intended to confirm its cytopathic effects over the same cell line and evaluate its potential over several other sorts of tumors. Therefore, we have performed a preliminary anti-proliferative activ- ity test over glioblastomas and eight other different cell lines. This first test confirmed the anti-proliferative effect of the ZVp over GBMs, since it showed 50% of cytostatic effect. Interestingly, the attenuated ZIKV prototype cyto- static effect has also been observed in six other tumors and one immortalized cell lines. Noteworthy, the most affected cell lines were prostate and ovarian tumor cells, where cytostatic effect was most evident. It has been recently observed that ZIKV presents tropism for uro- genital cells [49–51], and our results show that the ZVp presented a similar tropism, even after inactivation by heat. Although prostate and ovarian cells were the most affected, the attenuated ZIKV prototype still presents potential to interfere with other 6 cell lines that have also shown cytostatic effect, mainly glioblastoma, which is the most studied cell line with respect to ZIKV infection.
In Alzheimer’s disease (AD), glucose hypometabolism is con- sidered a typical feature of the disease at clinical stages, indi- cating the loss of neuronal function in specific brain regions . Cerebral glucose hypometabolism, characterized by im- paired glucose uptake and utilization related to brain insulin resistance [2, 3], and progressive mitochondrial dysfunction with aging  have both been recently associated with AD and suggest involvement of energy metabolism alterations in AD pathophysiology. Importantly, these alterations in early AD may occur both at the central nervous system (CNS) and the systemic level and play a role in clinical disease pro- gression [5, 6]. Despite these observations, the extent and sig- nificance of CNS and systemic metabolic alterations in AD remain poorly understood. Therefore, further and in-depth characterization of metabolic alterations to unravel potential new targets for therapeutic intervention is needed. Metabolo- mics is a powerful phenotyping technology, which allows to systematically identify and quantify the active small molecule-metabolite complement of cells, tissues, or biofluids and provide a sensitive and highly specific multiparametric measure of disease phenotype at the molecular level [7–14].
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etiology. Mikulicz’s syndrome was termed conditions involving enlargement of the same glands as a result of systemic diseases like leukemia, lymphosarcoma, tuberculosis and sarcoidosis. It was only in 1953, Morgan and Castleman concluded that Mikulicz disease and SS are identical, sharing the same histopathological features. It was reported that the histopathological changes of lymphocytic infiltration, acinar atrophy and cystic or solid duct alterations were seen in both diffusely enlarged salivary glands of patients with xerostomia as well as in localized salivary gland nodules of patients who were otherwise asymptomatic. This was termed as benign lymphoepithelial lesion. Similar findings noted in symptomatic individuals was regarded as SS.
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Metabolic alterations consist of the conver- sion from aerobic to anaerobic myocardial cell metabolism, thus producing biochemical changes of lactate, and cellular polarity. At a single-cell level a cascade is feasible, however cellular events will not occur synchronously in all cells beyond a stenosis. It is the later stages of the ischaemic cascade concept that are of clinical interest, but these can be subject to confounding effects of concomitant medica- tions and varying degrees of coronary disease. If the ischaemic cascade is not as solid a sequence as is often portrayed, this article discusses how the process of ischaemia could be conceptualised, the implications this has on the development of new tests of ischae- mia and the implications for clinical practice. Some clinicians and scientists may have already rejected the ischaemic cascade for not being true; for them, our paper is attack- ing a ‘ straw man ’ . Unfortunately however, ﬁ gures and slides are commonly shown 21–24
These results, although preliminary in nature (these were obtained with a very small number of samples, 3 mice, 3 slices per mouse), do not evidence consistent differences between the two groups of mice in the first part of the response following the electrical stimulus. However, Fig 2 indicates a consistent difference in the second part of the response (overshoot), i.e., in the amplitude, and therefore also in the duration as well. Therefore, we can confirm that metabolic alterations previously showed in the stressed mice model (3) and evidenced as fasting hyperglycemia, probably due in part to unbalance of hypothalamus-pituitary- adrenal hormones, can be responsible for alterations evidenced in the brain of stressed mice as well, . Moreover, according to the present results, in the light of data in the literature, brain alterations can be put in relationship to mitochondrial function: in fact, Shuttleworth et al (7) showed that different glucose concentration in the bath solution may modulate overshoot in different directions. Other possibilities cannot be excluded. For example previous experiments in the literature indicate that modulation of the overshoot component is influenced by drugs which stimulate, or vice-versa inhibit, post-synaptic neuronal excitation, for example bicuculline or ouabain; also changes in the Na+ concentration of ACSF solution may influence the response (7). Neonatal repeated stressful procedures induce alterations of several receptorial families, e.g., those related to the GABA and the opioid systems (see ref (8). Therefore, much experimental work is necessary before giving correct interpretation of our data, and on the role played by receptorial systems in the “overshoot” phenomenon produced in the somatosensorial cortex in our experiments.
Unlike the hippocampal area that, according to our find- ings, was much more susceptible to the effects of hypoxic than hyperoxic treatment after antecedent cerebral isch- emia, the fronto-parietal and occipital cortices were simi- larly sensitive to both treatments. However, metabolic alterations in both cortical areas were modest, compared with those in the hippocampus. Lac concentrations increased in both cortical areas by both treatments, but the effects of hypoxia were stronger than those of hyperoxia, in both young and aged rats. This difference probably reflects the prevalence of anaerobic metabolism when ischemia is associated with hypoxia, whereas hyperoxia may compen- sate, in part, for the deleterious effects of ischemia. The increase in Lac in cortical areas reflects neuronal damage, since unchanged or slightly modified levels of NAA and Glu rather rule out the occurrence of neuronal death. A sim- ilar trend was followed by GABA, whose levels were reduced in the fronto-parietal cortex. Depletion of Glu and GABA tissue concentrations induced by hypoxia in the fronto-parietal cortex are probably consequent to their release elicited by the ischemic insult [27,28]. In contrast, GABA concentration was significantly increased in the occipital cortex of both young and aged rats after ischemia- hyperoxia.
asiatic acid with its antioxidant and anti-inflammatory activity, improved hemodynamic and metabolic alterations in diet-induced metabolic syndrome . Asiatic acid has also been shown to ameliorate insulin resistance and oxidative stress and reduce inflammatory markers in mice hepatic tissues, resulting in protection from high fat diet-induced hepatic injury . In streptozotocin induced diabetic rats, asiatic acid attenuated hyperlip- idemia and hyperglycemiavia regulating key enzyme in lipid metabolism . Other biological effects of asi- atic acid have been demonstrated. Wang revealed anti- glycative effects of asiatic acid that related to decreasing oxidative stress and inflammation in human keratinocyte cells . Antihypertensive effects of asiatic acid in animal model hypertension has been reported to involve the modulation eNOS/p 47phox protein expression .
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The significant effect of period on AST concentration indicated variations across different months. AST is an enzyme that catalyses the transamination of amino acids, and higher levels in the blood can be indicative of changes in liver function, probably due to physiological alterations or rather adjustments. The changes in AST may not be attributed to changes in THI, but some physiological disorder due to probably blood collection timing, enzymatic and metabolic functions.has shown that quality of protein in diets may be responsible for changes in AST. In addition slight mouldin diets due to aflatoxins when the humidity is high has been shown to alter physiological functions in domestic animals including rabbits.Since, it was indicated that low protein diets could elicit certain physiological stress, due to metabolic demand for amino acids to maintain nitrogen balance for the body system .In contrast, changes in AST had been shown to be considered as a consequent action of cortisol on gluconeogenesis in the liver.Generally changes in serum enzymes activities seems to be correlated to biological functions of metabolically active organs and also levels of plasma proteins.
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nucleus suggests that the metabolic changes of the left lenticular nucleus play a more important role in T2DM. It is probable that the left hemisphere is more vulnerable than the right because of a “dominant hemisphere” effect. All subjects in the study were right-handed, which might explain why metabolite changes were more obvious in the left hemisphere. We speculated that the dom- inant hemisphere is more likely to be in the state of energy short- age because its energy requirements might be higher. Under hy- poxic conditions, this would make this hemisphere more susceptible to nerve tissue damage, metabolic abnormalities, and dysfunction.
It has been well documented that atherosclerotic vascular alterations may start early in life and progress with age. The first signs of hyperlipidemia can be detected in childhood 24 and fatty streaks, which are the earliest pathologic lesions of the atherogenic process, can be observed in the aorta and coronary arteries of individuals by the age of 20. Thus, recent studies have focused on the incidence of vascular risk factors and a higher risk of atherosclerosis development among children with epilepsy; however, this link has not yet been firmly established and remains controversial 25, 26, 27, 28 .
Background: Acute myeloid leukaemia (AML) is a malignancy that is heterogeneous in nature characterized by genetic abnormalities some of which are established in the diagnosis and prognosis of the disease. An additional role for alterations in epigenetic mechanisms has been also highlighted in the pathogenesis of the disease. This may have a role in determining the disease outcome, impact the treatment decision and provide options for targeted therapies especially in patients who lack genetic aberrations. One of the modes of epigenetic dysregulation is mutation in genes encoding isocitrate dehydrogenase 1 and 2 that has been observed in AML with a higher incidence in patients with normal karyotype (NK).
Metabolomics approaches can be targeted or non-targeted. Targeted metabolomics refers to the quantitative measurement of a select group of metabolites (e.g. amino acids, lipids, sugars, and/or fatty acids) in order to investigate specific metabolic pathways or to validate biomarkers identified using non-targeted metabolic profiling . Targeted approaches require a priori knowledge of metabolites of interest and known compounds, are based on metabolite-specific signals, and do not achieve global coverage . In contrast, non-targeted metabolomics approaches involve global profiling of the metabolome. This approach is typically employed in hypothesis-generating studies such as biomarker discovery, where comprehensive metabolite identification is generally not the goal . Thus, non- targeted metabolomics often provides more information than targeted metabolomics, but targeted metabolomics typically is more quantitative.
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Oncogenic Ras promotes metabolic reprogramming of can- cer epithelia by enhancing glucose uptake, glycolytic activity, and a shift to glutamine metabolism in a cell-autonomous manner. Glutamine is considered a conditionally essential amino acid, particularly for cells under stressed conditions, such as cancer. To maintain tumor growth, the carbon and nitrogen from glutamine become essential for active biosynthesis. The additional conver- sion of glutamine to glutamate, available through glutaminase activity (GLS and GLS2), can support the high energy needs of cancer cells, as its subsequent metabolism to α-ketoglutarate is an entry point for the TCA cycle and oxidative phosphorylation. Elevated blood glutamate is reported to be associated with higher grade PCa (20). Nevertheless, the role of glutamine/glutamate in energetics and cellular biomass does not seem to address its association with tumor aggressiveness. It is not clear whether ADT is selective or causative of aggressive recurrent PCa. Our study explores the expanding role of ADT on stromal epigenetic changes and paracrine glutamine signaling contributing to epi- thelial therapeutic resistance.
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In recent years, awareness that trace elements play a very important role, either beneficial or harmful, in human health has increased. Many metabolic disorders in man are accompanied by alterations in the concentration of one or more trace elements in some body fluid, especially blood serum or plasma. Interest in trace-element research in clinical medicine, biology, environmental studies, toxicology, and nutrition has become an exciting frontier, and during the last two decades the number of publications on this subject has progressively increased. Recent developments in instrumentation have lowered the limits for determining many trace elements to the low nanogram or even picogram range, thus enabling determination of parts per billion (ng/g) and, in some cases, even less. The present needs for trace measurements and techniques for micro- and sub microanalysis are already substantial, and recent reports indicate that the requirements and demands for such capabilities will increase considerably. Because most essential trace metals are present in biological specimens in very low concentrations, precise and accurate analysis is most essential if meaningful results are to be obtained. In this context, the various factors that influence the precision and accuracy of trace-metal analysis must be identified and controlled. Contamination and the stability of standards and controls are among the more important of these factors.
Abstract: Metabolic abnormalities are common in cancers, and targeting metabolism is emerg- ing as a novel therapeutic approach to cancer management. Pituitary adenoma (PA) is a type of benign tumor. Impairment of tumor cells’ metabolism in PA seems not to be as apparent as that of other malignant tumor cells; however, aberrant hormone secretion is conspicuous in most PAs. Hormones have direct impacts on systemic metabolism, which in turn, may affect the progres- sion of PA. Nowadays, conventional therapeutic strategies for PA do not include modalities of adjusting whole-body metabolism, which is most likely due to the current consideration of the aberrant whole-body metabolism of PA patients as a passive associated symptom and not involved in PA progression. Because systemic metabolic abnormalities are presented by 22.3%–52.5% PA patients and are closely correlated with disease progression and prognosis, we propose that assessment of metabolic status should be emphasized during the treatment of PA and that control of metabolic abnormalities should be added into the current therapies for PA.
The role of soy in ameliorating meta- bolic syndrome and its associated risk factors is an emerging area of nutrition research. Rodent models have demon- strated that soy diets can reduce adipos- ity and circulating cholesterol levels and improve insulin sensitivity (Davis et al. 2007; Ronis et al. 2009). Human studies have also supported the protective effects of soy against risk factors associated with metabolic syndrome. Postmenopausal women with the syndrome who con- sumed soy nuts showed improvements in glycemic control and blood lipids as well as a marker of inflammation (Azadbakht et al. 2007). In contrast, adults with type 2 diabetes who consumed soy protein had beneficial changes in blood lipid profiles but not glycemic control (Pipe et al. 2009). Hypertensive, postmenopausal women who consumed soy nuts had improve- ments in blood pressure that were associ- ated with markers of endothelial function, suggesting a decrease in vascular inflam- mation (Welty et al. 2007).
significant levels in any other group. Although colonization with Helicobacter can often remain harmless, the LPS and other antigens associated with the genus have shown the potential to induce a low-level systemic and vascular in- flammatory tone in the host which may exacerbate athero- genesis . Moreover, current infections with Helicobacter pylori have been associated with an altered, atherogenic lipid profile . Increased LPS levels in host circulation characterize the low-level chronic inflammation, termed metabolic endotoxaemia, which is associated with high fat- induced metabolic dysfunction . This scenario is thought to occur through increased intestinal permeability, which allows inflammatory bacterial fragments from the in- testinal microbiota, such as LPS, to pass into circulation . Bates et al.  demonstrated that LPS exposure trig- gered an increase in countervailing IAP expression, as the enzyme acts to detoxify the contaminant by dephosphoryla- tion of the highly inflammatory lipid A moiety. All high fat- fed groups in this study, bar OBG, presented with elevated IAP levels when compared to NC-fed mice. This coincides with elevated Proteobacteria-relative abundances and vis- ceral fat mass levels in these groups—effects from which OBG mice appeared to be afforded protection. The present study is possibly the longest run high fat-feeding trial avail- able to report IAP levels in a mouse model, and thus, we propose that animals experiencing the greatest level of chronic endotoxemia may require augmentation of IAP ex- pression to prevent low-level septicemia during high fat consumption.
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connectivity between each seed RoI and all other RoI measured was defined by the variable importance to the projection (VIP) statistic gained from PLSR analysis. A significant functional connection between brain regions was considered to exist if the 95% confidence interval (CI) of the VIP statistic exceeded 0.8, denoting a considerable contribution of the explanatory variable (RoI) to the dependent variable (seed region) in PLSR analysis. The SD and CI of the VIP statistic were estimated by jack-knifing. The significance of WIN 55,212-2 induced alterations in the VIP statistic were determined by t-test with post-hoc Bonferroni correction for multiple comparisons. WIN 55,212-2 induced alterations in functional connectivity on this basis were thus defined as being significant increases or reductions in functional connectivity (where the value of the VIP statistic is significantly altered between the groups but the 95% CI of the VIP statistic exceeds the 0.8 threshold in both experimental groups), or significantly lost or newly gained functional connectivity (WIN 55,212-2-treated animals significantly different from controls and the 95% CI of the VIP statistic exceeds the 0.8 threshold in only one of the experimental groups) .
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