Gamma-glutamyl transferase variability can predict the development of end-stage of renal disease: a nationwide population-based study.

The aim of this study is to investigate whether GGT variability is able to predict the risk of end-stage renal disease (ESRD). The study subjects were Koreans who conducted health exams supported by the Korean National Health Insurance Corporation during 2009-2012 (baseline). After excluding individuals aged < 40 years, heavy alcoholics, or those with histories of chronic liver disease or ESRD, we followed 6,058,995 individuals.

Author Correction: Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade.

Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha-2-HS-glycoprotein.

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes.

Transcriptional activation of p21(WAF¹/CIP¹) is mediated by increased DNA binding activity and increased interaction between p53 and Sp1 via phosphorylation during replicative senescence of human embryonic fibroblasts.

Although p21(WAF1/CIP1) is known to be elevated during replicative senescence of human embryonic fibroblasts (HEFs), the mechanism for p21 up-regulation has not been elucidated clearly. In order to explore the mechanism, we analyzed expression of p21 mRNA and protein and luciferase activity of full-length p21 promoter. The result demonstrated that p21 up-regulation was accomplished largely at transcription level.

Antidiabetic and Beta cell-protection activities of purple corn anthocyanins.

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice.

ATM mediates interdependent activation of p53 and ERK through formation of a ternary complex with p-p53 and p-ERK in response to DNA damage.

DNA damage in eukaryotic cells induces signaling pathways mediated by the ATM, p53 and ERK proteins, but the interactions between these pathways are not completely known. To address this issue, we performed a time course analysis in human embryonic fibroblast cells treated with DNA-damaging agents. DNA damage induced the phosphorylation of p53 at Ser 15 (p-p53) and the phosphorylation of ERK (p-ERK).

Effect of combined treatment with progesterone and tamoxifen on the growth and apoptosis of human ovarian cancer cells.

Progesterone has a potential protective effect against ovarian carcinoma induced by estrogen. Progesterone is also known to cause apoptosis while tamoxifen induces growth arrest. Therefore, we attempted to determine whether combined treatment with progesterone and tamoxifen has a synergistic effect on anti-cancer activity.

Higher DNA repair activity is related with longer replicative life span in mammalian embryonic fibroblast cells.

Since the detailed comparison of DNA repair activities among mammalian embryonic fibroblast cells with different replicative life spans has not been investigated, we tested DNA repair activities in embryonic fibroblast cells derived from mammals including human, dog, rat, and mouse. The cell viability after treatment of four DNA damage agents appeared to be decreased in the order of human embryonic fibroblasts (HEFs) > dog embryonic fibroblasts (DEFs) > rat embryonic fibroblasts (REFs) > mouse embryonic fibroblasts (MEFs) although statistical significance was lacking. The amounts of strand breaks and AP (apurinic/apyrimidinic) sites also appear to be decreased in the order of HEFs > DEFs > REFs ≥ MEFs after treatment of DNA damage agents.

Calorie restriction (CR) reduces age-dependent decline of non-homologous end joining (NHEJ) activity in rat tissues.

Even though CR has shown to enhance base excision repair (BER) and nucleotide excision repair (NER) capacities, it has not been reported whether CR can enhance non-homologous end joining (NHEJ) activity. To examine the effect of CR on NHEJ activity, ad libitum (AL)- and calorie restricted (CR)-dieted rats were used. Age-dependent decline of NHEJ activity was apparent in the lung, liver, and kidney and appeared to be slightly decreased in spleen.

ERK mediates anti-apoptotic effect through phosphorylation and cytoplasmic localization of p21Waf1/Cip1/Sdi in response to DNA damage in normal human embryonic fibroblast (HEF) cells.

Since anti-apoptotic effect of ERK has not been elucidated clearly in DNA-damage-induced cell death, the role of ERK was examined in normal HEF cells treated with mild DNA damage using etoposide or camptothecin. ERK was activated by DNA damage in HEF cells. PD98059 increased apoptosis and reduced DNA-damage-induced p21Waf1/Cip1/Sdi level.

Nitric oxide is an essential mediator for neuronal differentiation of rat primary cortical neuron cells.

Nitric oxide (NO) regulates proliferation, differentiation and survival of neurons. Although NO is reported to involve in NGF-induced differentiation of PC12 cells, the role of NO has not been characterized in primary neuron cells. Therefore, we investigated the role of NO in neuronal differentiation of primary cortical neuron cells.

Nicotinamide reduces dopamine in postnatal hypothalamus and causes dopamine-deficient phenotype.

Dopamine is an important neurotransmitter in the human central nervous system and also plays a key role in the development of postnatal brains. We previously reported that nicotinamide, a SIRT1 inhibitor, regulates tyrosine hydroxylase (TH) expression in vitro. To investigate the effect of nicotinamide-mediated TH regulation in vivo, nicotinamide was chronically injected into neonatal mice.

SIRT1 regulates tyrosine hydroxylase expression and differentiation of neuroblastoma cells via FOXO3a.

To examine the function of SIRT1 in neuronal differentiation, we employed all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. Nicotinamide inhibited neurite outgrowth and tyrosine hydroxylase (TH) expression. Inhibition of PARP or histone deacetylase did not inhibit TH expression, showing the effect to be SIRT1 specific.

Preparation and properties of collagen/modified hyaluronic acid hydrogel for biomedical application.

Hydrogels composed of collagen and hyaluronic acid are types of crosslinked water-swellable polymers and possess vast potential for applications in the medical industry. Collagen (Co) is the major structural protein of connective tissues such as skin, tendon and cartilage. Hyaluronic acid (HA) is a non-immunogenic, non-adhesive glycosaminoglycan that has a high water absorption property and plays significant roles in several cellular processes.

The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress.

The inducible 70 kDa heat shock proteins (Hsp70) in mice are encoded by two almost identical genes, hsp70.1 and hsp70.3.

COX-2 regulates p53 activity and inhibits DNA damage-induced apoptosis.

We have previously shown that p53 induces cyclooxygenase-2 (COX-2) expression and COX-2 inhibits p53- or genotoxic stress-induced apoptosis. However, the COX-2 effects have been demonstrated indirectly by the use of a selective inhibitor, NS-398, and the molecular mechanisms by which COX-2 inhibits apoptosis have not been identified. In the present study, we demonstrated that COX-2 inhibits genotoxic stress-induced apoptosis by using an adenoviral COX-2 overexpression system.