Many cancer treatments are associated with serious side effects, while they often only benefit a subset of the patients. Therefore, there is an urgent clinical need for tools that can aid in selecting the right treatment at diagnosis. Here we introduce simulated treatment learning (STL), which enables prediction of a patient's treatment benefit. STL uses the idea that patients who received different treatments, but have similar genetic tumor profiles, can be used to model their response to the alternative treatment. We apply STL to two multiple myeloma gene expression datasets, containing different treatments (bortezomib and lenalidomide). We find that STL can predict treatment benefit for both; a twofold progression free survival (PFS) benefit is observed for bortezomib for 19.8% and a threefold PFS benefit for lenalidomide for 31.1% of the patients. This demonstrates that STL can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment.

Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL (p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health.

A study was conducted to determine the effects of zearalenone (ZEN) on the mRNA expression of pregnane X receptor (PXR), constitutive and rostane receptor (CAR), and phase I and II enzymes as well as the toxicity in the liver of female weanling piglets. Thirty-two female weanling piglets (Duroc × Landrace × Large white, 12.27 ± 0.30 kg)were divided into four groups (n = 8 piglets/group) that were supplemented with 0 (control), 0.5, 1 or 2 mg/kg ZEN. The trial period lasted for 28 d. The results showed that the ZEN supplementation in the diets (0.5-2 mg/kg) had no effect on growth performance but dose-dependently increased serum aspartate aminotransferase, alanineaminotransferase, alkaline phosphatase, and γ-glutamyltransferase activities (P < 0.05). The ZEN residue in the liver (P < 0.01) was also linearly and dose-dependently increased. Furthermore, the mRNA expression of PXR, CAR, phase I enzymes (i.e., cyp2e1, cyp3a5, cyp2a6, cyp1a1, and cyp1a2), and phase II enzymes (i.e., gsta1, gsta2, ugt1a3) significantly increased linearly in a dose-dependent manner (P < 0.05). However, the spleen relative weight and the glutathione peroxidase activity in the liver (P < 0.05) linearly decreased as the dietary ZEN concentration increased; the mRNA expression of the nuclear receptors PXR and CAR is responsive to ZEN in female piglets, and ZEN increases the mRNA expression of their target genes. This finding shows that the nuclear receptor signaling system plays an important role in the defense against ZEN.

Inhibition of the mechanistic target of rapamycin (mTOR) protein kinase extends life span and ameliorates aging-related pathologies including declining immune function in model organisms. The objective of this phase 2a randomized, placebo-controlled clinical trial was to determine whether low-dose mTOR inhibitor therapy enhanced immune function and decreased infection rates in 264 elderly subjects given the study drugs for 6 weeks. A low-dose combination of a catalytic (BEZ235) plus an allosteric (RAD001) mTOR inhibitor that selectively inhibits target of rapamycin complex 1 (TORC1) downstream of mTOR was safe and was associated with a significant (P = 0.001) decrease in the rate of infections reported by elderly subjects for a year after study drug initiation. In addition, we observed an up-regulation of antiviral gene expression and an improvement in the response to influenza vaccination in this treatment group. Thus, selective TORC1 inhibition has the potential to improve immune function and reduce infections in the elderly.

Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor.

High expression of cluster of differentiation (CD)39 and CD73 has cardio-protective effects. We hypothesised that the expression of CD39 and CD73 would differ between propofol- and volatile anaesthetic-based anaesthesia in patients undergoing open heart surgery (OHS). The objective of this prospective randomized trial was to compare the changes in CD39 and CD73 levels in CD4+ T cells between propofol- and sevoflurane-based anaesthesia during OHS. The study randomly allocated 156 patients undergoing OHS to a propofol or sevoflurane group. Blood was obtained preoperatively and up to 48 hours after weaning from cardiopulmonary bypass (CPB). The expression levels of CD39 and CD73 in circulating CD4+ T cells, serum cytokines and other laboratory parameters were analysed. The primary outcome was the expression of CD39 and CD73 on CD4+ T cells. Demographic data and perioperative haemodynamic changes did not show significant differences between the two groups. The expression of CD39 and CD73 in the sevoflurane group was significantly lower than in the propofol group (P < 0.001). Other laboratory findings including cardiac enzymes and cytokine levels, did not show significant intergroup differences. Propofol attenuated the decrease in CD39 and CD73 in circulating CD4+ T cells compared to sevoflurane-based anaesthesia during OHS.

Recently, resveratrol showed induction of γ-globin mRNA synthesis in human erythroid precursors and reducing oxidative stress in red cells of thalassemia patients in many in vitro studies. We aimed to investigate the efficacy and safety of resveratrol, for the first time, in non-transfusion-dependent beta-thalassemia intermedia (B-TI) in Southern Iran. In this double-blind randomized clinical trial, 54 patients with B-TI were investigated during 6 months between October 2016 and March 2017. Patients were randomly allocated into three groups by simple randomization method. Group 1 (hydroxyurea (HU) and placebo, 18 patients), group 2 (resveratrol/piperine and placebo, 16 patients), and group 3(HU and resveratrol/piperine, 20 patients). Primary end point was considered as change in hemoglobin (Hb) levels and need for blood transfusion. Drug safety was considered as a secondary end point. Mean age of the patients was 28.2 ± 5.6 (18-42) years. Response rate was not significantly different among the three groups (P > 0.05). Higher percentages of adverse events were detected in groups 2 (31.3%) and 3 (25%) compared to group 1 (5.6%). However, the difference was not statistically significant (P > 0.05). All reported adverse events were gastrointestinal symptoms. Resveratrol showed a similar efficacy with HU in the small population of non-transfusion B-TI patients during a 6-month follow-up. Complications, mostly gastrointestinal, were observed more frequently in resveratrol groups compared to the HU group. Although it was not statistically significant, more attention should be given to safety and efficacy of resveratrol as an oral HbF-augmenting agent.

In type 2 diabetes impaired insulin-induced muscle perfusion is thought to contribute to reduced whole-body glucose uptake. In this study, we examined the effects of iloprost, a stable prostacyclin analogue, on insulin-induced muscle capillary recruitment and whole-body glucose uptake.

Nutritional supplementation can have beneficial effects on body composition, strength, and function in older adults. However, whether the response of satellite cells can be altered by nutritional supplementation in older adults remains unknown.

Both obesity and high dietary fat intake activate the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome.

During current research, the effects of deoxynivalenol (DON) exposure on cerebral lipid peroxidation, neurotransmitter secretion and calcium homeostasis in chicks were evaluated. One hundred and twenty Hailan chicks (male, 1-day-old) were randomly divided into four groups. Chicks in low, medium and high dose groups were fed with 0.27, 1.68 and 12.21 mg/kg-1 DON respectively by gavage according to feed intake. Chicks in control group were fed with physiological saline by gavage. The trials were conducted for 36 d. At the end of the trials, twenty chicks per group were sacrificed, and the cerebra were collected for measuring the brain indices. Compared with the control group, the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase were significantly decreased in treatment groups (P < 0.05), the contents of malondialdehyde in high dose group were increased (P < 0.05), the catalase activities and nitric oxide contents in medium and high dose groups were decreased (P < 0.05), and the activities of T-AOC in high dose group were reduced (P < 0.05). Compared with the control group, the concentrations of norepinephrine and 5-hydroxytryptamine in high dose group were obviously increased (P < 0.05), while the concentrations of dopamine were decreased (P < 0.05). Meanwhile, the concentrations of calcium and calmodulin (CaM) in medium and high dose groups were lower than those of the control group (P < 0.05), and the gene relative expression of CaM mRNA in treatment groups were significantly reduced (P < 0.05), in a dose-dependent manner. These results suggested that DON exposure can affect the cerebral lipid peroxidation, neurotransmitters secretion and the balance of calcium homeostasis in chicks.

A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy.

In livestock, feeding a reduced nitrogen (N) diet is favored for economic and ecological reasons. Ruminants cope more easily with a reduced N diet than monogastric species. However, changes in mineral homeostasis such as a reduction in 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) concentrations, calcium (Ca), and IGF1 levels were observed in goats kept on a reduced N diet. The decrease in 1,25-(OH)2D3 occurred even during a simultaneous reduction in dietary N and Ca, whereas a solitary Ca reduction stimulated 1,25-(OH)2D3 synthesis. The aim of the present study was to examine the effects of N- and/or Ca-reduced diets on the expression of 24-hydroxylase (CYP24A1), 1-alpha-hydroxylase (CYP27B1), vitamin D receptor (VDR), retinoid X receptor alpha (RXRα), IGF1 receptor (IGF1R), Klotho, and fibroblast growth factor receptor 1c (FGFR1c) in kidneys of young goats. Four groups were kept on a control diet, an N-reduced diet, a Ca-reduced diet or an N- and a Ca-reduced diet. Renal expression of CYP24A1 was not affected, whereas CYP27B1 expression was significantly diminished in the N-reduced diet fed goats (P < 0.05) and significantly elevated with the Ca reduction (P < 0.001). The VDR expression was not modified, whereas RXRα (P < 0.05) and Klotho expression (P < 0.001) were stimulated during Ca reduction. The IGF1R (P < 0.05) and FGFR1c (P < 0.05) expression were enhanced with the N reduction. From these data, it can be concluded that the downregulation of renal CYP27B1 expression observed with dietary N reduction is probably mediated by a complex interaction between the somatotropic axis and the Klotho/FGF signaling pathway in young goats.

Depression is a common affective disorder or mood disorder, which seriously affects people's physical and mental health and the quality of life. This study compared efficacy of escitalopram and fluoxetine on depression patients, and analyzed the inflammatory factors, serum homocysteine (Hcy) levels and the effects of adverse reactions, so as to provide reference for the clinical. The results showed that the total effective rate of the observation group (90.7%) was higher than that of the control group (80%), but the difference was not statistically significant (p>0.05). The total score of Hamilton Depressive Scale (HAMD) and mood in the observation group was significantly lower than that in the control group after treatment. To sum up, escitalopram and fluoxetine are effective in the treatment of depressive patients, but escitalopram can significantly improve the patient's micro inflammation and depressive symptoms Keywords: Fluoxetine, escitalopram, clinical efficacy, interleukin, mental anxiety, drug reaction.

Activation of gastrointestinal (GI) sweet taste receptors by caloric sweeteners triggers secretion of anorexigenic and inhibition of orexigenic GI hormones to regulate food intake. The effect of noncaloric sweeteners on these mechanisms is controversial. We have recently shown that motilin-induced gastric phase III contractions signal hunger feelings, thereby identifying GI motility, and its regulatory hormone motilin, as novel players in food intake regulation.

Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear.

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 &times; 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.

Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring.

Motilin plasma concentrations are positively correlated with hunger ratings during the fasting state. Moreover, the motilin agonist erythromycin stimulates meal requests.

The decrement in plasma glucose concentration with SGLT2 inhibitors (SGLT2i) is blunted by a rise in endogenous glucose production (EGP). We investigated the ability of incretin treatment to offset the EGP increase. Subjects with type 2 diabetes (n = 36) were randomized to 1) canagliflozin (CANA), 2) liraglutide (LIRA), or 3) CANA plus LIRA (CANA/LIRA). EGP was measured with [3-3H]glucose with or without drugs for 360 min. In the pretreatment studies, EGP was comparable and decreased (2.2 ± 0.1 to 1.7 ± 0.2 mg/kg ⋅ min) during a 300- to 360-min period (P < 0.01). The decrement in EGP was attenuated with CANA (2.1 ± 0.1 to 1.9 ± 0.1 mg/kg ⋅ min) and CANA/LIRA (2.2 ± 0.1 to 2.0 ± 0.1 mg/kg ⋅ min), whereas with LIRA it was the same (2.4 ± 0.2 to 1.8 ± 0.2 mg/kg ⋅ min) (all P < 0.05 vs. baseline). After CANA, the fasting plasma insulin concentration decreased (18 ± 2 to 12 ± 2 μU/mL, P < 0.05), while it remained unchanged in LIRA (18 ± 2 vs. 16 ± 2 μU/mL) and CANA/LIRA (17 ± 1 vs. 15 ± 2 μU/mL). Mean plasma glucagon did not change during the pretreatment studies from 0 to 360 min, while it increased with CANA (69 ± 3 to 78 ± 2 pg/mL, P < 0.05), decreased with LIRA (93 ± 6 to 80 ± 6 pg/mL, P < 0.05), and did not change in CANA/LIRA. LIRA prevented the insulin decline and blocked the glucagon rise observed with CANA but did not inhibit the increase in EGP. Factors other than insulin and glucagon contribute to the stimulation of EGP after CANA-induced glucosuria.