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关键词： biochemical recurrence   IL-8   IL-23   TNF-alpha  

摘要： Background Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets. Methods Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables. Results Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-alpha (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-alpha correlated with IL-23 (r = .72;P < .001) and IL-8 (r = .59;P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57;P < .001) and MIP-3 alpha (r = .56;P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-alpha levels above the median (P = .042). Conclusions Several innate cytokines were associated with

关键词： BONE QCT   mu CT   BONE QUALITY   CHRONIC KIDNEY DISEASE-MINERAL BONE DISORDER (CKD-MBD)   VASCULAR CALCIFICATION  

摘要： Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder that affects blood measures of bone and mineral homeostasis, vascular calcification, and bone. We hypothesized that the accumulation of advanced glycation end-products (AGEs) in CKD may be responsible for the vascular and bone pathologies via alteration of collagen. We treated a naturally occurring model of CKD-MBD, the Cy/+ rat, with a normal and high dose of the AGE crosslink breaker alagebrium (ALT-711), or with calcium in the drinking water to mimic calcium phosphate binders for 10 weeks. These animals were compared to normal (NL) untreated animals. The results showed that CKD animals, compared to normal animals, had elevated blood urea nitrogen (BUN), PTH, FGF23 and phosphorus. Treatment with ALT-711 had no effect on kidney function or PTH, but 3 mg/kg lowered FGF23 whereas calcium lowered PTH. Vascular calcification of the aorta assessed biochemically was increased in CKD animals compared to NL, and decreased by the normal, but not high dose of ALT-711, with parallel decreases in left ventricular hypertrophy. ALT-711 (3 mg/kg) did not alter aorta AGE content, but reduced aorta expression of receptor for advanced glycation end products (RAGE) and NADPH oxidase 2 (NOX2), suggesting effects related to decreased oxidative stress at the cellular level. The elevated total bone AGE was decreased by 3 mg/kg ALT-711 and both bone AGE and cortical porosity were decreased by calcium treatment, but only calcium improved bone properties. In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD. (c) 2019 American Society for Bone and

关键词： Conference   education   FEBS   Israel   IUBMB   Weizmann  

摘要： The New Horizons in Biochemistry and Molecular Biology Education Conference was organized by the International Union of Biochemistry and Molecular Biology (IUBMB) in collaboration with the Federation of European Biochemical Societies (FEBS), and the Weizmann Institute of Science (Israel) and held in Rehovot, Israel, on September 6-8, 2017. The program covered the entire lifespan of students/scientists from the school level to undergraduate, graduate, and post-doctoral levels and brought together 130 international participants. This article provides an overview of the major issues and topics discussed at the conference and suggestions for the way forward.

关键词： Anoxia   Hypoxia   Oxidative stress   Osmolyte   Sugar metabolism   Gene expression   Trichoderma harzianum  

摘要： We studied the role of Trichoderma harzianum (TH) in improving the physiological, biochemical, hormonal, and molecular parameters of tomato seedlings grown under waterlogging (WL, for 14 and 28 days). Pretreatment with TH significantly improved the growth of tomato by enhancing the chlorophyll synthesis and uptake of essential ions, including nitrogen, phosphorus, and potassium. A reduction in anthocyanin content was also ameliorated significantly by TH pretreatment. TH significantly mitigated the WL-induced decline in height and in fresh and dry biomass accumulation. Accumulation of proline, flavonoids, anthocyanin, sugars, and soluble protein increased with TH pretreatment. At both growth periods (14 and 28 days after treatment [DAT]), the accumulation of secondary metabolites, including total phenols and flavonoids, and the redox components (tocopherols) were increased significantly by TH pretreatment. Increased synthesis of metabolites maintained the antioxidant status of tomato, resulting in amelioration of WL-induced oxidative effects on membranes. WL and TH treatments significantly increased ethylene production and decreased abscisic acid content at both growth periods. The accumulation of reactive oxygen species, like hydrogen peroxide, in TH treated seedlings was correlated with the upregulation of the Fe-SOD gene. WL stress triggered the activity of sucrose synthase (SUS), lactate dehydrogenase (LDH), and pyruvate decarboxylase (PDC), which reached a maximum at 14 DAT, and TH pretreatment resulted in further enhancement above control and WL-stressed levels. Quantitative RTPCR revealed differential expression of genes, where Fe-SOD and ADH were upregulated due to TH treatment and ARE, AGO, ERF, and aquaporin were downregulated relative to control plants. Pretreatment of tomato seedlings with TH improved tolerance to WL by maintaining the antioxidant status, sugar metabolism, and expression of critical genes. These results suggest that TH pretreatment is an

关键词： Fetal physiology   Abnormal Offspring Syndrome   Cloning by nuclear transfer   Cattle  

摘要： The aim of this study was to compare metabolic profiles of maternal and fetal blood and liver gene expression patterns of Day-225 bovine fetuses produced either in vivo (IVD) by superovulation and artificial insemination, or in vitro by in vitro fertilization (IVF) or by Handmade Cloning (NT-HMC). Biochemical evaluations were performed in fetal and maternal plasma and the expression of key genes to fetal development were analyzed by RT-qPCR in fetal liver tissue. In addition to group comparisons, data were also used for correlation analyses with physical traits using simple correlation test and AN(C)OVA. Most fetal parameters related to liver and kidney functions and hemoglobin metabolism, and the osmolalities in fetal plasma and placental fluids were higher in clones than the other two groups. Glucose, fructose, triglycerides and VLDL concentrations in fetal plasma, concentration of fructose and total amount of glucose and fructose in the allantoic fluid were higher in clones. Differences in the relative gene expression in fetal liver were also detected for genes related to fructose and glucose metabolism, sugar transport, and fatty acid and cholesterol metabolism. In conclusion, important differences in the metabolism of cloned concepti were identified and suggest active fructose accumulation and lipid synthesis, which may be associated with metabolic fetal programming and excessive prenatal growth.

关键词： Prostate-specific membrane antigen   Prostate cancer   PSMA-PET-CT   Management impact   Ga-68-THP-PSMA  

摘要： Purpose To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of Ga-68-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). Methods One hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before Ga-68-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of Ga-68-THP-PSMA (mean 159 +/- 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded. Results HR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 mu g/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 mu g/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 mu g/L, 0%;PSA 0.5-1.0 mu g/L, 35%;PSA 1.0-5.0 mu g/L, 69%;PSA 5.0-10.0 mu g/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%). Conclusions Ga-68-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 mu g/L.

关键词： Dogs   dialysis   diffusion   kidney diseases  

摘要： Intermittent hemodialysis (IHD) is a type of kidney replacement therapy commonly prescribed in veterinary medicine for cases of drug removal, fluid, acid-base, and electrolyte disorders, acute kidney injury, and cases of chronic kidney disease (CKD) in uremic crisis. This study aimed to evaluate the effects of intermittent hemodialysis in dogs with IRIS stage 4 CKD in contrast to dogs treated only with standard medical management, without dialysis, to improve their quality of life. Twenty-five dogs previously diagnosed with IRIS stage 4 CKD were selected for the study according to the inclusion criteria. Dogs were randomized to 2 distinct groups: the control group (n = 11), which underwent a conventional clinical treatment for CKD;and the hemodialysis group (n = 14), which underwent intermittent hemodialysis in addition to the clinical treatment. Both groups had a period of 15 days of clinical and laboratory evaluation. Laboratory analysis consisted of chemistry and hematological evaluation before and after both treatments at a minimum interval of 48 hours. Clinical parameters and eventual complications were assessed every 30 minutes during the IHD. When compared with conventional treatment, IHD was highly efficient in removing urea, creatinine, and phosphorus, but presented a hematological risk to the patient, requiring constant monitoring of hematological and biochemical profiles in order to correct alterations. Therefore, IHD is a highly recommended treatment if adequately monitored by trained professionals. (C) 2019 Elsevier Inc. All rights reserved.

关键词： atherosclerosis   dyslipidemia   hypercholesterolemia   lipid panel   atorvastatin   statin   psittacine   bird   avian   Amazon parrot   Amazona ventralis  

摘要： Atorvastatin is a synthetic statin administered in its active form and used for the treatment of dyslipidemias. In the current study, the effects of atorvastatin were evaluated on plasma lipid profiles and the potential for adverse effects after once daily PO dosing of atorvastatin for 30 days in Hispaniolan Amazon parrots (Amazona ventralis). Sixteen adult parrots (10 female, 6 male) with hypercholesterolemia were used for this study. Birds were assigned to 2 groups (treatment and control) of 8 parrots each (3 male, 5 female) after balancing for age, sex, originating institution, and baseline plasma cholesterol values. Compounded atorvastatin oral suspension (10 mg/kg) was administered PO once daily via gavage into the crop. Equivalent volumes of placebo suspension were administered to the control group. Plasma biochemistry and plasma lipid profile analysis (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TGs]) were analyzed on days 0, 14, and 30. Plasma samples and HDL-C fractions were evaluated for cholesterol and TG concentrations via enzymatic assays. Subtraction of HDL-C values from total cholesterol yielded the non-HDL-C concentration for each bird. Birds were routinely assessed for appetite, activity, and urofeces. Plasma atorvastatin concentrations were obtained from 7 of 8 birds in the treatment group from banked samples. Those samples were obtained on days 14 and 30, with drug administration 6 to 8 hours before collection. No significant differences were observed in total cholesterol, HDL-C, non-HDL-C, or TG between treatment and control groups at days 0, 14, and 30. Plasma atorvastatin concentrations were variable on day 14 (0.54-5.41 ng/mL for 6 of 7 samples, with 1 outlier of 307 ng/mL) and on day 30 (0.79-6.74 ng/mL). No adverse effects were noted in any of the birds during the study period. When dosed PO at 10 mg/kg once daily, atorvastatin did not result in significant

关键词： Apple   Abscisic acid   Antioxidant enzymes   Abiotic stress-responsive transcription factors   Drought stress  

摘要： Water scarcity is one of the major factors limiting apple production. Partial root-zone drying (PRD) is a water-saving irrigation technique necessary to improve the efficiency of irrigation techniques to optimize the amount of fruit produced with the volume of water used. The apple trees cv. Red Delicious were exposed to four treatments, including (1) control with 100% of the crop evapotranspiration (ETc) needs;(2) alternate partial root-zone drying with 75% of the ETc needs (APRD75);(3) fixed partial root-zone drying with 75% of the ETc needs (FPRD75);(4) fixed partial root-zone irrigation with 50% of the ETc needs (FPRD50) in a semiarid region of Iran. Results showed that leaf water potential (psi(leaf)), and chlorophyll were significantly decreased in FPRD50 compared to control and other PRD treatments. APRD75 and FPRD75 treatments significantly enhanced ( +)-catechin (+C), epicatechin (EC), chlorogenic acid (CGA), caffeic acid (CA) as well as increased water use efficiency (WUE) (by 30-40% compared to control) without significant reduction of yield. PRD reduced gibberellic acid (GA3) and kinetin, while, increased the abscisic acid (ABA) and salicylic acid (SA) levels. The abiotic stress-responsive transcription factors (TFs) MdoMYB121, MdoMYB155, MdbZIP2, and MdbZIP48 were highly expressed in all PRD treatments. Our results demonstrated that APRD75 and FPRD75 have the potential to stimulate antioxidant defense mechanisms, hormonal signaling pathways, and expression of drought-tolerance TFs to improve WUE while maintaining crop yield. Therefore, APRD75andFPRD75 with water savings as compared to full irrigation might be a suitable strategy for irrigation apple trees under water scarcity.

关键词： Bioreactor technique   Mechanical strain   Contractile phenotype  

摘要： Vascular tissue engineering of the middle layer of natural arteries requires contractile smooth muscle cells (SMC) which can be differentiated from adipose-derived mesenchymal stem cells (ASC) by treatment with transforming growth factor-beta, sphingosylphosphorylcholine and bone morphogenetic protein-4 (TSB). Since mechanical stimulation may support or replace TSB-driven differentiation, we investigated its effect plus TSB-treatment on SMC orientation and contractile protein expression. Tubular fibrin scaffolds with incorporated ASC or pre-differentiated SMC were exposed to pulsatile perfusion for 10 days with or without TSB. Statically incubated scaffolds served as controls. Pulsatile incubation resulted in collagen-I expression and orientation of either cell type circumferentially around the lumen as shown by alpha smooth muscle actin (alpha SMA), calponin and smoothelin staining as early, intermediate and late marker proteins. Semi-quantitative Westernblot analyses revealed strongly increased alpha SMA and calponin expression by either pulsatile (12.48-fold;p < 0.01 and 38.15-fold;p = 0.07) or static incubation plus TSB pre-treatment (8.91-fold;p < 0.05 and 37.69-fold;p < 0.05). In contrast, contractility and smoothelin expression required both mechanical and TSB stimulation since it was 2.57-fold increased (p < 0.05) only by combining pulsatile perfusion and TSB. Moreover, pre-differentiation of ASC prior to pulsatile perfusion was not necessary since it could not further increase the expression level of any marker.