Association between rs738409 and rs2896019 single-nucleotide polymorphisms of phospholipase domain-containing protein 3 and susceptibility to nonalcoholic fatty liver disease in Greek children and adolescents.

Background: Several studies have detected a strong association linking rs738409 and rs2896019 polymorphisms in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene with hepatic steatosis and steatohepatitis. In the present study we aimed to determine the association of those PNPLA3 variants with nonalcoholic fatty liver disease (NAFLD) susceptibility in obese and nonobese Greek children and adolescents.

Methods: The study recruited 91 children and adolescents of Greek descent with NAFLD or biopsy-proven nonalcoholic steatohepatitis, and 91 healthy subjects of normal weight (control group) with sex distribution similar to the patient group.

Influence of conception and delivery mode on stress response marker and imprinted gene expression related to embryo development: A cohort study.

Background: Recent scientific data support that the mode of conception and delivery may influence epigenetic regulation and therefore embryo development. Octamer-binding transcription factor 4-B1 , a novel variant of OCT4 with yet unknown biological function, is suggested to have a potential role in mediating cellular stress response. Furthermore, , and are genes known as imprinted and are regulated via means of epigenetic regulation.

In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health.

Background: Genomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus.

Resveratrol supports and alpha-naphthoflavone disrupts growth of human ovarian follicles in an in vitro tissue culture model.

Infertility is a global health problem with an estimated incidence of 15%. Exposure to chemicals is a potential causal factor, and there is a lack of studies examining the effects on female germ cells. Here, we have studied the impact of different aryl hydrocarbon receptor (AHR) modulators on human ovarian follicles using a human ovarian tissue culture model.

Potentiation by caffeine of cytogenetic damage induced by steroidal derivatives in human lymphocytes in vitro.

We studied the effects of three newly synthesized steroidal derivatives of nitrogen mustards, alone or in combination with caffeine, on sister chromatid exchange (SCE) frequencies and on human lymphocyte proliferation kinetics. The agents have as alkylator functionalities either P-N,N-bis(2-chloroethyl)aminophenyl-buturate (CHL) or P-N,N-bis(2-chloroethyl)aminophenyl-acetate (PHE), esterified with a modified steroidal nucleus. An enhancement of SCE frequency was seen with compounds which contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17-position of the D-ring.

Differential expression of IL-17, 22 and 23 in the progression of colorectal cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with GM-CSF and IFN-γ.

Recent studies have suggested that aberrant K-ras signaling is responsible for triggering immunological responses and inflammation-driven tumorigenesis. Interleukins IL-17, IL-22, and IL-23 have been reported in various types of malignancies, but the exact mechanistic role of these molecules remains to be elucidated. Given the role of K-ras and the involvement of interleukins in colorectal tumorigenesis, research efforts are reported for the first time, showing that differentially expressed interleukin IL-17, IL-22, and IL-23 levels are associated with K-ras in a stage-specific fashion along colorectal cancer progression.

Cytogenetic and antineoplastic effects by newly synthesised steroidal alkylators in lymphocytic leukaemia P388 cells in vivo.

New compounds with potential antitumour activity were synthesised by combining nitrogen mustard with the steroidal skeleton, in an effort to improve specificity and at the same time reduce systemic toxicity. The steroidal part is aimed to serve as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties. The purpose of the present investigation was to evaluate these compounds for anti-neoplastic activity.

Synergistic cytogenetic and antineoplastic effects by the combined action of esteric steroidal derivatives of nitrogen mustards.

We studied the effect of five newly synthesized steroidal derivatives of nitrogen mustards. These derivatives have as alkylators either P-N, N-bis(2-chloroethyl)aminophenyl-butyrate (CHL) or P-N, N-bis(2-chloroethyl)aminophenyl-acetate (PHE) groups esterified with different modified steroidal nuclei. We examined them alone or in combination, on sister chromatid exchange rates and on human lymphocyte proliferation kinetics.

Cytogenetic activity of newly synthesized 1,5-benzodiazepines in normal human lymphocyte cultures.

Introduction: Many different types of benzodiazepine medications exist to treat a wide array of psychological and physical diseases based on dosage and implications. Benzodiazepines are generally considered as safe and effective drugs in short term; however, cognitive impairments and paradoxical effects occasionally occur. Our recent studies have shown that some 1,4-benzodiazepines exhibit cytogenetic activity (alprazolam, diazepam, and lorazepam) in normal human lymphocyte cultures.

The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.

The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients (five males, three females). Patients were treated for 12 weeks with either metformin (850 mg x 3) or matching placebo using a double-blind crossover study design; patients were studied at presentation and at the end of each treatment period. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) before and during a 4-hour hyperinsulinemic euglycemic clamp (100 mU.

Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man.

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained.

The effect of sulphonylurea therapy on skeletal muscle glycogen synthase activity and insulin secretion in newly presenting type 2 (non-insulin-dependent) diabetic patients.

Ten newly presenting, Type 2 (non-insulin-dependent), Caucasian diabetic patients were studied before and after 8 weeks treatment with the sulphonylurea gliclazide, and in parallel 13 similar patients were studied before and after 8 weeks treatment with diet alone. Eight non-diabetic subjects were also studied. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) prior to and during a 4-h hyperinsulinaemic euglycaemic clamp (100 mU kg-1 h-1).

Impaired activation of skeletal muscle glycogen synthase in non-insulin-dependent diabetes mellitus is unrelated to the degree of obesity.

Twenty-five newly presenting, untreated, white, non-insulin-dependent diabetic (NIDDM) subjects were studied within 72 hours of diagnosis. They were allocated to three groups according to their body mass index [BMI] (lean BMI less than 25.0, n = 9; overweight BMI 25.

Effects of intensive dietary treatment on insulin-stimulated skeletal muscle glycogen synthase activation and insulin secretion in newly presenting type 2 diabetic patients.

Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240-min insulin infusion (100 mU kg-1 h-1).

In vitro study of human skeletal muscle strips: effect of nonesterified fatty acid supply on glucose storage.

To examine the effect of increased nonesterified fatty acid concentration on glucose storage in human muscle, an in vitro method for study of glycogen synthesis in this tissue has been established. Muscle strips obtained from rectus abdominus during elective abdominal surgery were clamped at resting length, and adenosine triphosphate/total adenosine nucleotide ratios remained constant for 3 hours ex vivo. Leakage of enzyme markers of muscle damage was minimal, and electron microscopy showed preserved myofibril ultrastructure.

Insulin-like and insulin-inhibitory effects of monoclonal antibodies for different epitopes on the human insulin receptor.

Monoclonal antibodies previously shown to react with five distinct epitopes on the human insulin receptor were tested for their metabolic effects on isolated human adipocytes. Two antibodies which reacted with receptor alpha-subunit and completely inhibited 125I-insulin binding mimicked the actions of insulin to stimulate lipogenesis from [14C]glucose and to inhibit catecholamine-induced lipolysis. On a molar basis, these antibodies were comparable in potency with insulin itself.