This study was conducted to determine the effects of fish oil administration on gene expression related to insulin, lipid and inflammation in women with polycystic ovary syndrome (PCOS).

Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes (T2D). In vitro and animal studies have shown that resveratrol exerts an antioxidant effect, but clinical trials addressing this effect in patients with T2D are limited. The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a randomized, placebo-controlled, double-blind clinical trial.

We previously demonstrated the anti-inflammatory and antioxidant effects of exenatide. We now hypothesized that exenatide also increases the plasma concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti-inflammatory protein, and modulates the nuclear factor erythroid 2‒related factor‒Kelchlike ECH-associated protein 1‒antioxidant response element (Nrf-2‒Keap-1‒ARE) system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress.

Sodium glucose co-transporter 2 (SGLT2) inhibitors have been associated with increased serum ketone body levels in patients with type 2 diabetes mellitus (T2DM). In the present analysis we evaluated serum ketone body levels and variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. The median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β-hydroxybutyrate. Approximately two-thirds of the variability in each ketone measure was attributed to intra-subject variability. Intra-subject variability was higher for serum ketones than other metabolites. Patients in the lowest response tertile exhibited no increase in ketones. Those in the highest response tertile tended to be male and have higher fasting plasma glucose levels, lower insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum ketones were not fully explained by changes in plasma fatty acids, suggesting downstream effects of SGLT2 inhibition on hepatic metabolism that favour ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were greater and more variable than changes in other metabolic measures in Japanese patients with T2DM.

The fibroblast growth factor 23 (FGF23) response to phosphate load is suppressed in adiponectin gene null mice and substantially amplified in mice overexpressing the same gene and vitamin D receptor (VDR) activation markedly enhances FGF23 gene expression.

Little is known about the effects of desflurane associated or not with nitrous oxide (N2O) on oxidative stress and patient genetic material. The aim of this study was to compare the effects of anesthesia maintained with desflurane associated or not with N2O on DNA damage (as a primary outcome) and oxidative stress (as a secondary outcome) in patients who underwent an elective minimally invasive surgery.

Atmospheric ammonia in animal housing is reported to have adverse effects on livestock performance and animal health. Previous experiments have found that 75 ppm ammonia reduced the production performance and altered body fat distribution quality of broilers. In this study, we examined the body fat distribution, serum metabolites and lipid metabolism gene expression of broiler exposed to ammonia. A total of 400 chickens were randomly allocated to four groups with four replicates and received ammonia treatments at 0, 25, 50 and 75 ppm, respectively, for 3 weeks. The average daily feed intake and weight gain were decreased when broiler was exposed to ammonia concentration exceeding 50 ppm (p < .05). The increased abdominal fat and reduced thickness of subcutaneous adipose were found in broilers of 75 ppm group (p < .05). When ammonia exceeded 50 ppm, the content of fat in breast muscle of broiler was increased, and when ammonia was higher than 25 ppm, the fat in liver was increased (p < .05). It showed that the fat content in liver was a sensitive index for broilers exposed to ammonia. Furthermore, ammonia exposure had no significant effect on total cholesterol and triglyceride in serum, but significantly increased the relative mRNA expression of acetyl-CoA carboxylase (p = .046) and malic enzyme in liver (p = .038), which indicated that ammonia exposure may increase the de novo fat synthesis in liver. In addition, ammonia increased the high-density lipoprotein cholesterol (p = .02) and activity of hepatic lipase in serum (p < .001), which indicated that ammonia exposure may improve the transportation of cholesterol to liver. To conclude, our results indicated that ammonia exposure might increase the de novo fat synthesis in liver and increased the transportation of cholesterol to liver. In addition, the concentration of ammonia in poultry house should be limited lower than 25 ppm based on the variation of hepatic fat content.

Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.

Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies.

The brain death of a potential organ donor induces a systemic inflammatory response, resulting in inferior organ quality and function. Our study aimed to evaluate the effects of methylprednisolone (MPN) therapy on pattern recognition receptor (PRR) signaling in potential brain-dead (BD) kidney donors.

Migraine is an episodic headache, which is an endothelial disorder with neurological inflammation. Intercellular Adhesion Molecule-1 (ICAM-1), as an endothelial factor, leads to the adhesion of leukocytes to the walls of the cerebral blood vessels, which is an important step in the inflammation process. Curcumin and omega-3 fatty acids, by affecting transcription factors, can regulate the gene expression and serum levels of ICAM-1. Thus, this study aimed to evaluate the synergistic effects of ω-3 fatty acids and nano-curcumin on ICAM-1 gene expression and serum levels in migraine patients.

Endometriosis is an estrogen-dependent disease. The impaired estrogen and progesterone signaling over-activates the Wnt/β-catenin pathway in endometriosis patients, which can explain the increased invasion potency of endometrial cells derived from the endometrium of women with endometriosis. The regulatory effects of vitamin D on Wnt/β-catenin pathway were demonstrated by previous studies. According to gene prioritization method, among Wnt target genes, CD44 was in high ranking in relation to endometriosis. The aim of this study is to investigate the expression of CD44 in the endometrium of women with endometriosis and to study the effects of vitamin D on its expression. This prospective study was performed, during a 12 months period from December 2015 to November 2016, on healthy women as the control group (n = 14) and endometriosis patients (n = 34). The endometriosis patients randomly divided into two groups: One group treated according to the routine protocol and the other group, alongside the routine protocol, took 50,000 IU vitamin D weekly for 12-14 weeks. Blood, endometrial fluid, and endometrial tissue samples were obtained from the control group and endometriosis groups before and after the intervention. We used in silico gene prioritization to study the relevance of CD44. The expression of CD44 was evaluated using the techniques of Western blot, real-time polymerase chain reaction, and ELISA. The eutopic endometrium of women with endometriosis in mid-secretory phase expressed significantly higher levels of CD44s, CD44V, and CD44v6. The concentration of soluble CD44 in the serum and endometrial fluid of endometriosis patients was higher than of healthy women. The expression level of CD44s, CD44V, and CD44v6 in the eutopic endometrium as well as the concentration of soluble CD44 in the endometrial fluid was decreased after modification of the circulating levels of 25(OH)D. It seems that the increased expression and extensive shedding of CD44 in eutopic endometrium play a role in the pathogenesis of endometriosis. Vitamin D can control and modify this process at least in part. We suggest more in vivo investigations on the therapeutic potency of vitamin D in endometriosis.

Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism. Multiparous Holstein cows between 3 and 9 d in milk were screened 3 times per week and enrolled in the study when whole-blood β-hydroxybutyrate concentrations measured ≥1.2 mmol/L. Cows were randomly allocated to 1 of 4 groups: (1) 500 mL of a 50% d-glucose solution intravenously once a day for 3 d (n = 8), (2) 300 mL of propylene glycol orally once a day for 3 d (n = 8), (3) 500 mL of a 50% d-glucose solution intravenously and 300 mL of propylene glycol orally once a day for 3 d (n = 8), or (4) an untreated control group (n = 8). Liver biopsies were taken on the day of enrollment as well as on the day following completion of treatments. Liver triglyceride and glycogen content were determined by colorimetric and fluorometric methods, respectively. Gene and protein expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase 1, glucose-6-phosphatase, 3-hydroxy-3-methylglutaryl-CoA synthase 2, acetyl-CoA carboxylase, and carnitine palmitoyltransferase 1A were compared between groups and time points using quantitative reverse transcriptase PCR and Western blotting techniques, respectively. In addition, the ratio of light chain 3B II:I was determined by Western blotting. Plasma samples from both time points for each enrolled cow were submitted for chemistry analysis. Data were analyzed using a repeated-measures ANOVA taking into account the paired nature of the data, and differences between all groups and time points were controlled for multiple comparisons using the Tukey procedure. No difference was found in triglyceride or glycogen concentration between treatment groups. The gene expression of pyruvate carboxylase decreased in the group receiving both treatments, whereas protein expression of this enzyme increased in all groups over time. The autophagy marker light chain 3B II:I decreased in the group receiving both glucose and propylene glycol. No other changes in gene or protein expression of key hepatic enzymes were associated with treatments. We conclude that intravenous glucose and oral propylene glycol, commonly used treatments for ketosis in postpartum dairy cows, administered alone or in combination for a duration of 3 d did not have important beneficial or detrimental effects on selected indicators of liver composition and function in cows with hyperketonemia.

Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg pluronic nanoparticles). Serum miR-155 level was measured by real-time quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH), aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra) were measured. Weighted mean difference (WMD), relative risk (RR), complications, surgery infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores were used to evaluate therapeutic efficacy. After 1-month therapy, infection rates and side effects were lower in OG than those in PG (RR =0.64, 95% confidence interval [CI] [0.48, 0.84], P=0.001). The fusion rates were higher in OG than in PG (WMD =21.96, 95% CI [-0.24, 37.62], P=0.021). The JOA scores were higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], P=0.007), and no significant difference was found for the visual analog scale and Oswestry Disability Index. Serum levels of miR-155, ALT, AST, and IL-1β were lower while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased the levels of ALT, AST, and IL-1β and reduced the levels of SOD, GSH, and IL-1ra. In contrast, miR-155 inhibitor had reverse results. Therefore, ONAS has better improvement in complications and therapeutic effects on DLD by regulating serum miR-155.

The purpose was to assess the developmental competence of the in vitro or in vivo matured human oocytes as well as the apoptotic genes expression of cumulus cells (CCs) regarding nuclear maturity status of associated oocytes retrieved from stimulated ICSI cycles. A total of 590 oocytes and the associated CCs were retrieved and divided into groups of test and control according to the nuclear maturity status in order to the developmental evaluation as well as expression patterns of apoptosis-related genes using real time PCR. The fertilization and embryo formation rates were 60.3% and 87.5% vs.69.1% and 92.8% in test and control groups, respectively. Good quality embryos on day 3 were 62.2% in test and 69.1% in control groups. There were significant differences in the rates of normal fertilized as well as unfertilized oocytes between the groups. Also, mRNA levels of some apoptotic genes were significantly higher in the CCs obtained from immature oocytes among patients with premature ovarian factors (POF) rather than other infertility etiologies (p < 0.001). The data demonstrated the developmental competence of in vitro matured oocytes -even to good quality cleavage embryos- is not completely consistent with molecular integrity and well-mannered gene expression patterns resulting to ICSI success. It seems that using immature oocytes could be helpful for patients at risk of ovarian hyperstimulation syndrome (OHSS) as the same as patients with diminished ovarian reserve.

In the current study, we aimed to identify nanocurcumin effects on microRNAs (miRNAs) in the peripheral blood of patients with relapsing-remitting multiple sclerosis (RRMS). We intended to investigate the expression pattern of these miRNAs in experimental settings in vivo. The expression levels of the selected 27 miRNAs known to be involved in the regulation of immune responses were analyzed in 50 RRMS patients and 35 healthy controls. The miRNA expression profiles were investigated by quantitative PCR (qPCR) at baseline and after 6 months of nanocurcumin therapy. Our data revealed that the expression of a number of microRNAs including miR-16, miR-17-92, miR-27, miR-29b, miR-126, miR-128, miR-132, miR-155, miR-326, miR-550, miR-15a, miR-19b, miR-106b, miR-320a, miR-363, miR-31, miR-150, and miR-340 is regulated by nanocurcumin. The results of the current work indicate that nanocurcumin is able to restore the expression pattern of dysregulated miRNAs in MS patients. We discovered that some miRNAs are deregulated in untreated patients compared with healthy controls and nanocurcumin-treated patients. This is a new finding that might represent the potential contribution of these miRNAs to MS pathogenesis. Taken together, these data provide novel insights into miRNA-dependent regulation of the function of B and T cells in MS disease and enrich our understanding of the effects mediated by a therapeutic approach that targets B and T cells.

To evaluate expression of progesterone receptor (PGR) AB in follicle stimulating hormone (FSH)-treated or non-treated sheep administered with arginine (Arg) or saline (Sal) fed a control (C), excess (O) or restricted (U) diet, uterine tissues were collected at the early, mid and/or late luteal phases. In exp. 1, ewes from each diet were randomly assigned to one of two treatments, Arg or Sal administration three times daily from day 0 of the first estrous cycle until uterine tissue collection. In exp. 2, ewes were injected twice daily with FSH on days 13-15 of the first estrous cycle. Uterine tissues were immunostained to detect PGR followed by image analysis. PGR were detected in luminal epithelium (LE), endometrial glands (EG), endometrial stroma (ES), myometrium (Myo), and endometrial and myometrial blood vessels. The percentage of PR-positive cells and/or intensity of staining were affected by phase of the estrous cycle, plane of nutrition, and/or FSH but not by Arg. In exp. 1, percentage of PGR-positive cells in LE and EG but not in ES and Myo was greater at the early and mid than late luteal phase, was not affected by plane of nutrition, and was similar in LE and EG. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in LE, EG and Myo, and was the greatest in LE, less in EG, and least in ES and Myo. In exp. 2, percentage of PGR-positive cells in LE, EG, ES and Myo was affected by phase of the estrous cycle, but not by plane of nutrition; was greater at the early than mid luteal phase; and was greatest in LE and EG, less in luminal (superficial) ES and Myo and least in deep ES. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in all compartments but ES, and was the greatest in LE and luminal EG, less in deep EG, and least in ES and Myo. Comparison of data for FSH (superovulated) and Sal-treated (non-superovulated) ewes demonstrated that FSH affected PR expression in all evaluated uterine compartments depending on plane of nutrition and phase of the estrous cycle. Thus, PGR are differentially distributed in uterine compartments, and PGR expression is affected by nutritional plane and FSH, but not Arg depending on phase of the estrous cycle. Such changes in dynamics of PGR expression indicate that diet plays a regulatory role and that FSH-treatment may alter uterine functions.

Inflammation of the uterus and oviduct is associated with reduced reproductive performance in humans and domestic animals. Toll-like receptors are expressed in various immune and non-immune cells and play a crucial role in innate immunity. Toll-like receptor - 4 (TLR4) can detect lipopolysaccharide (LPS) from Gram-negative bacteria leading to the secretion of pro-inflammatory cytokines, chemokines, antimicrobial peptides and other inflammatory mediators. To investigate the effects of a local inflammation on the expression levels of TLR4 and pro-inflammatory cytokines, 12 female rabbits received an intracervical infusion with either saline solution endotoxin-free (carrier, 2 mL; n = 6) or LPS (500 μg diluted in 2 mL of saline solution; n = 6). Blood samples were performed at 0, 30, 60 and 90 min and 2,4,6 and 24 h after treatment to evaluate interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) plasma concentrations. Animals were sacrificed 24 h post-treatment. The uterus and oviducts were immediately collected. The gene expression and protein levels of TLR4 and pro-inflammatory cytokines were detected by quantitative real-time PCR (qRT-PCR) and immuno-histochemical assay, respectively. Our study showed that the intracervical administration of LPS induced local inflammation given that the animals showed no clinical signs, the histological samples revealed signs of inflammation and plasma levels of pro-inflammatory cytokines were unchanged compared to the control. LPS produced an increase in the TLR4 mRNA expression levels in the uterus with respect to the control (P < 0.05). In LPS-treated rabbits the gene expression of IL-1β was higher in the uterus and oviducts and TNF-α only in the oviduct (P < 0.05) as compared to the control. The immuno-histochemical assay showed that TLR4, IL-1β and TNF-α were expressed in the reproductive tissues of the rabbit. Moreover, after the LPS stimulation the stromal cells of the uterus exhibited a higher staining for TLR4 (P < 0.05) and the epithelial cells of the oviduct for TNF-α and IL-1β (P < 0.05) with respect to the control. These results suggest that (1) TRL4, IL-1β and TNF-α are expressed in uterus and oviducts of the doe, and (2) LPS up-regulates the gene and protein expression of TLR4 and pro-inflammatory cytokines in uterus and oviducts. Therefore, the rabbit could be a useful animal model for studying the local mechanisms involved in reproductive dysfunctions caused by subclinical infections.

Blood transfusion therapy is lifesaving for individuals with β-thalassemia major (β-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with β-TM.