Strategies to improve the early diagnosis of prostate cancer will provide opportunities for earlier intervention. The blood-based prostate-specific antigen (PSA) assay is widely used for prostate ...cancer diagnosis but specificity of the assay is not satisfactory. An algorithm based on serum levels of PSA combined with other serum biomarkers may significantly improve prostate cancer diagnosis. Plasma glycan-binding IgG/IgM studies suggested that glycan patterns differ between normal and tumor cells. We hypothesize that in prostate cancer glycoproteins or glycolipids are secreted from tumor tissues into the blood and induce auto-immunoglobulin (Ig) production. A 24-glycan microarray and a 5-glycan subarray were developed using plasma samples obtained from 35 prostate cancer patients and 54 healthy subjects to identify glycan-binding auto-IgGs. Neu5Acα2-8Neu5Acα2-8Neu5Acα (G81)-binding auto-IgG was higher in prostate cancer samples and, when levels of G81-binding auto-IgG and growth differentiation factor-15 (GDF-15 or NAG-1) were combined with levels of PSA, the prediction rate of prostate cancer increased from 78.2% to 86.2% than with PSA levels alone. The G81 glycan-binding auto-IgG fraction was isolated from plasma samples using G81 glycan-affinity chromatography and identified by N-terminal sequencing of the 50 kDa heavy chain variable region of the IgG. G81 glycan-binding 25 kDa fibroblast growth factor-1 (FGF1) fragment was also identified by N-terminal sequencing. Our results demonstrated that a multiplex diagnostic combining G81 glycan-binding auto-IgG, GDF-15/NAG-1 and PSA (≥ 2.1 ng PSA/ml for cancer) increased the specificity of prostate cancer diagnosis by 8%. The multiplex assessment could improve the early diagnosis of prostate cancer thereby allowing the prompt delivery of prostate cancer treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Physical inactivity and unhealthy food intake are strongly associated with the growing prevalence of type 2 diabetes (T2D). Dyslipidemia, a characteristic of T2D patient, contributes to an increase ...in intra-myocellular lipid accumulation and mitochondria dysfunction, in skeletal muscle cells and further to insulin resistance. The aim of this study was to evaluate the effect of aerobic exercise on dyslipidemia, mitochondrial homeostasis and mitochondrial DNA (mtDNA) transcription in T2D- induced animals. Wistar rats (8 weeks old) were fed a diet containing 60% fat over 9 weeks, at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). At week 3 of the experiment half of the animals started on an aerobic exercise 5-days/week. Blood and soleus muscle were collected at 9th experimental week. Abdominal fat, blood glucose, triglyceride, low-density-lipoprotein and high-density lipoprotein (HDL), and cellular mtDNA copy number, cytochrome b (cytb) mRNA and 8-isoprostane were measured. T2D-induced animals exhibited changes in blood glucose, weight gain, abdominal fat, LDL and muscular 8-isoprostane, mtDNA copy number and cytb mRNA. Aerobic exercise attenuated the increase in weight gain and abdominal fat and the decreased cytb mRNA, and increased HDL. Our results suggest that aerobic exercise might not affect all characteristics related to the development of T2D in the same way. However, since T2D is a multifactorial disease, improvement in parameters such as HDL levels, abdominal fat and weight gain induced by aerobic exercise might delay or inhibit the onset of T2D.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
...several complications, such as cardiovascular events, retinopathy, neuropathy, and nephropathy, are induced in the population with diabetes and are the leading cause of mortality and morbidity ...3–5. In this way, this study found associations between genes related to inflammatory targets such as cytokines, nuclear transcription factors, growth factors, and energy balance. ...the results of this study 10 help to explain the molecular pathways involved in diabetes pathogenesis and provide new strategies for treatment, such as specifically reducing the degree of inflammation in pancreatic islets. Since pharmacological and nonpharmacological interventions for diabetes have been discussed based on inflammatory, oxidative, and proteostasis pathways 11, it is possible to propose that the compound could restore the number of β cells and islet function by connecting in silico, in vitro, animal models, and clinical data pieces of evidence, to possibly becoming effective in patients with failed insulin control, based on anti-inflammatory and insulin resistance properties. ...according to the reports analyzed in the present literature review, there is no consensus regarding the protective effect of supplementation of vitamin D on β cell function in T1DM. ...large-scale epidemiological studies are needed to evaluate the role of vitamin D in the development of T1DM.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Early identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a ...chemotherapeutic agent, have increased cardiac expression of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a bioactive lipid implicated in hypertension and coronary artery disease. However, the utility of 14,15-DHET as plasma biomarkers was not defined. The aim of this study is to investigate if levels of 14,15-DHET are an early blood biomarker to predict the subsequent occurrence of cardiotoxicity in cancer patients after chemotherapy.
H9c2 rat cardiomyocytes were treated with DOX (1 μM) for 2 h and levels of 14,15-DHET in cell media was quantified at 2, 6 or 24 h in media after DOX treatment. Similarly, female Sprague-Dawley rats were treated with DOX for two weeks and levels of 14,15-DHET was assessed in plasma at 48 h and 2 weeks after DOX treatment. Changes in brain natriuretic peptide (BNP) mRNA, an early cardiac hypertrophy process, were determined in the H9c2 cells and rat cardiac tissue. Results were confirmed in human subjects by assessment of levels of 14,15-DHET in plasma of breast cancer patients before and after DOX treatment and left ventricular ejection fraction (LVEF), a clinical marker of cardiotoxicity.
Levels of 14,15-DHET in cell media and rat plasma increased ~ 3-fold and was accompanied with increase in BNP mRNA in H9c2 cells and rat cardiac tissue after DOX treatment. In matched plasma samples from breast cancer patients, levels of 14,15-DHET were increased in patients that developed cardiotoxicity at 3 months before occurrence of LVEF decrease.
Together, these results indicate that levels of 14,15-DHET are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines. Increased levels of 14,15-DHET in plasma may be an important clinical biomarker for early detection of anthracycline-induced cardiotoxicity in cancer patients.
Abstract Changes in eating habits and sedentary lifestyle are main contributors to type 2 diabetes (T2D) development, and studies suggest that epigenetic modifications are involved with the growing ...incidence of this disease. Regular exercise modulates many intracellular pathways improving insulin resistance and glucose uptake in skeletal muscle, both early abnormalities of T2D. Mitochondria dysfunction and decreased expression of glucose transporter (GLUT4) were identified as main factors of insulin resistance. Moreover, it has been suggested that skeletal muscle of T2D subjects have a different pattern of epigenetic marks on the promoter of GLUT4 and PGC1, main regulator of mitochondrial function, compared with nondiabetic individuals. Recent studies have proposed that regular exercise could improve glucose uptake by the attenuation of such epigenetic modification induced at GLUT4, PGC1 and its downstream regulators; however, the exact mechanism is still to be understood. Herein we review the known epigenetic modifications on GLUT4 and mitochondrial proteins that lead to impairment of skeletal muscle glucose uptake and T2D development, and the effect of physical exercise at these modifications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sedentarism accounts for exacerbated fat storage in skeletal muscle that can impair mitochondrial biogenesis and progress to Type 2 Diabetes (T2D). A signaling pathway coordinated by coactivators and ...transcription factors such as myocyte stimulating factor 2 (MEF2), peroxisome proliferator-activated receptor 1-alpha (PGC1α), and mitochondrial transcription factor (TFAM) is essential to preserve mitochondrial function. So, we tested the effect of chronic physical exercise on the expression of MEF2, PGC1α, and TFAM, in gastrocnemius. Were analyzed lipidic profile, fasting glucose, and gene expressions (PGC1 α, TFAM, MEF2) in muscle obtained from Wistar rats divided into four groups: Control (fed with balanced chow and sedentary), Exercised (fed with balanced chow and exercised), T2D (fed with high-fat chow + a low dose of streptozotocin and sedentary) and T2D-exercised (fed with high-fat diet + a low dose of streptozotocin and exercised). Exercised group exhibited increased expression of PGC1α and MEF2 compared to the Control and T2D groups (sedentary or exercised). PGC1α was higher in Exercised by 143 % compared to Control, and by 220 % compared to T2D groups. MEF2 was 39 % higher in Exercised group when compared to the T2D group and 300 % higher than the exercised T2D group. High-Density Lipoprotein was positively associated with PGC1α expression, probably associated with the improvement in mitochondrial function in exercised animals, and fasting glucose was negatively associated with MEF2, probably related to impaired mitochondrial functioning in animals with T2D. We conclude that physical could improve some T2D harming effects by enhancing mitochondrial biogenesis and homeostasis.
•Physical exercise improve some T2D harming effects by enhancing mitochondrial biogenesis and homeostasis.•Physical exercise stimulates the expression of factors correlated to the mitochondrial biogenesis cascade, including PGC1α and MEF2.•High-Density Lipoprotein was positively associated with PGC1α expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obesity has become a worldwide pandemic as well as a major contributing factor to the increasing rate of type 2 diabetes (T2D). However, there is an intriguing variance demonstrated by a subset of ...obesity defined as metabolically healthy obesity (MHO). MHO individuals are less prone to develop obesity-related metabolic complications, such as metabolic syndrome (MetS) and further T2D. The exact reason why an MHO person does not present the cluster of risk factors associated with insulin resistance is unknown due to the challenge to mimic MHO in experimental settings. However, MHO individuals present lower sedentary behaviors in comparison to individuals with MetS, which might indicate that an adaptation to skeletal muscle, such as increased insulin sensitivity and glucose transporter (GLUT4), could play a major role in their healthy characteristics. The hypothesis invoked in this paper is that lower exposure to bisphenol together with increased levels of physical exercise underlie the physiological aspects behind MHO characteristics. Evidence suggests that exposure to “obseogens,” such as bisphenol A (BPA), appears to impair insulin secretion and insulin response in cells containing GLUT4. Epidemiological studies have associated higher levels of BPA, as well as bisphenol S and F, in children with a risk for MetS development. Therefore, the combination between low bisphenol exposure and increased physical exercise may not necessarily affect body weight, but it could modify several metabolic pathways inhibiting insulin resistance, which characterize the heathy status of the MHO. If confirmed, this hypothesis could lead to therapeutic approaches to reverse MetS and inhibit T2D onset.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bisphenol -A and –S (BPA and BPS), chemicals used in food packaging, have been associated with risk of insulin resistance and Type 2 diabetes (T2D) development. The aim of this study was to ...investigate the association between BPA, BPS and oxidative stress with lipid profiles and changes on blood glucose induced via aerobic exercise assessed by an oral glucose tolerance test (OGTT).
Male and female young adults (23.52 ± 2.47 yrs old) participated in 2 separate testing days. On both days, an OGTT was performed, wherein blood glucose was measured before Maltodextrin consumption and following 30-, 60-, and 75-min. On the exercising day, subjects ran for 30-min while they remained seated on the resting day. Urinary BPA, BPS and 8-isoprostane (a marker of oxidative stress) were assessed each day. Lipid profile, body fat percentage and physical fitness was also analyzed.
Blood glucose uptake of both experimental days was negatively associated with body fat (r = −0.52 resting and −0.51 exercising) and to 8-isoprostane on the exercising day (ρ = −0.47). Urinary BPA and BPS were positively associated with 8-isoprostane (ρ = 0.73, for both bisphenols). BPA and 8-isoprostane were negatively correlated with physical fitness (ρ = −0.58 and −0.74, respectively) while 8-isoprostane was negatively associated with increased HDL (ρ = −0.47).
The interrelation between 8-isoprostane and both BPA and BPS suggest that oxidative stress could be the link between the harmful effect of these chemicals on the human body.
•Oxidative stress mediates the adverse effect of bisphenols on human health.•Levels of urinary BPA and BPS are not associated with glucose uptake.•Physical fitness is negatively associated with levels of oxidative stress and bisphenol-A.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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