The final goal of regenerative periodontal therapy is to restore the structure and function of the periodontium destroyed or lost due to periodontitis. However, the role of periosteum in periodontal regeneration was relatively neglected while bone repair in the skeleton occurs as a result of a significant contribution from the periosteum. The aim of this study is to understand the histological characteristics of periosteum and compare the native periosteum with the repaired periosteum after elevating flap or after surgical intervention with flap elevation.

Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA). Metformin, a well-known anti-diabetic drug, inhibits hepatic gluconeogenesis in the liver. Many studies have shown that metformin not only prevented, but also reversed, steatosis and inflammation in a nonalcoholic steatohepatitis (NASH) animal model. However, the role of metformin in HSC activation and succinate-GPR91 signaling has not been clarified.

Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis.

Liver fibrosis is a progressive pathological process that accompanies wound healing; however, therapeutics for reversing hepatic fibrosis are unavailable. Activation of hepatic stellate cells (HSCs) play a critical role in liver fibrosis. Recent reports showed that succinate and its receptor, G-protein coupled receptor 91 (GPR91), act as signaling molecules during the activation of HSCs. However, the role of succinate in proliferation, apoptosis, and migration of HSCs has not been studied. In this study, we determined whether succinate regulates proliferation, apoptosis, and migration of HSCs and induces liver fibrosis in a mouse model. Succinate treatment not only induced activation of HSCs, but also increased the proliferation and migration of LX-2 HSCs and inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis, 100 mg/kg succinate or control PBS was administered by intraperitoneal injection to mice once a day for four weeks. There were significant molecular changes such as increased α-SMA and collagen type 1 production and increased production of inflammatory cytokines such as IL-6 and TNF-α, but not TGF-β, in the succinate-treated group compared to the control group. However, no morphological changes were observed in Masson's trichrome staining. In conclusion, the present study demonstrated that succinate induces activation, proliferation, and migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of succinate accumulation may be an effective method for reversing liver fibrosis by controlling HSC survival and growth.

During pregnancy, many women gain excessive weight, which is related to adverse maternal and neonatal outcomes. In this study, we evaluated whether rate of gestational weight gain (RGWG) in early, mid, and late pregnancy is strongly associated with adverse pregnancy outcomes. A retrospective chart review of 2,789 pregnant Korean women was performed. Weights were recorded at the first clinic visit, during the screening test for fetal anomaly, and during the 50g oral glucose challenge test and delivery, to represent early, mid, and late pregnancy, respectively. A multivariate logistic regression analysis was performed to examine the relationship between RGWG and adverse pregnancy outcomes. At early pregnancy, the RGWG was significantly associated with high risk of developing gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), large for gestational age (LGA) infants, macrosomia, and primary cesarean section (P-CS). The RGWG of mid pregnancy was not significantly associated with any adverse pregnancy outcomes. The RGWG at late pregnancy was significantly associated with a lower risk of developing GDM, preterm birth and P-CS, but with a higher risk of developing LGA infants and macrosomia. When the subjects were divided into three groups (Underweight, Normal, and Obese), based on pre-pregnancy body mass index (BMI), the relationship between early RGWG and adverse pregnancy outcomes was significantly different across the three BMI groups. At early pregnancy, RGWG was not significantly associated to adverse pregnancy outcomes for subjects in the Underweight group. In the Normal group, however, early RGWG was significantly associated with GDM, PIH, LGA infants, macrosomia, P-CS, and small for gestational weight (SGA) infants, whereas early RGWG was significantly associated with only a high risk of PIH in the Obese group. The results of our study suggest that early RGWG is significantly associated with various adverse pregnancy outcomes and that proper preemptive management of early weight gain, particularly in pregnant women with a normal or obese pre-pregnancy BMI, is necessary to reduce the risk of developing adverse pregnancy outcomes.

Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

In mammals, pain is regulated by the combination of an ascending stimulating and descending inhibitory pain pathway. It remains an intriguing question whether such pain pathways are of ancient origin and conserved in invertebrates. Here we report a new Drosophila pain model and use it to elucidate the pain pathways present in flies. The model employs transgenic flies expressing the human capsaicin receptor TRPV1 in sensory nociceptor neurons, which innervate the whole fly body, including the mouth. Upon capsaicin sipping, the flies abruptly displayed pain-related behaviors such as running away, scurrying around, rubbing vigorously, and pulling at their mouth parts, suggesting that capsaicin stimulated nociceptors in the mouth via activating TRPV1. When reared on capsaicin-containing food, the animals died of starvation, demonstrating the degree of pain experienced. This death rate was reduced by treatment both with NSAIDs and gabapentin, analgesics that inhibit the sensitized ascending pain pathway, and with antidepressants, GABAergic agonists, and morphine, analgesics that strengthen the descending inhibitory pathway. Our results suggest Drosophila to possess intricate pain sensitization and modulation mechanisms similar to mammals, and we propose that this simple, non-invasive feeding assay has utility for high-throughput evaluation and screening of analgesic compounds.

Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.

Rapid prenatal diagnosis of common chromosome aneuploidies have been successful through quantitative fluorescent PCR (QF-PCR) assays and small tandem repeat (STR) markers. The purpose of our study was to investigate the clinical feasibility for rapid prenatal detection of Down syndrome using the quantitative fluorescent PCR in uncultured amniocytes. DNA was extracted from uncultured amniotic fluid of normal karyotype (n=200) and of Down syndrome (n=21). It was amplified using QF-PCR with four STR markers located on chromosome 21. Among normal samples, the ranges of diallelic peaks for at least one STR marker were 1.0-1.3 for D21S11, 1.0-1.4 for D21S1411 and 1.0-1.5 for D21S1270. Down syndrome samples showed trisomic triallelic patterns or trisomic diallelic patterns. The sensitivity, specificity, and efficiency of the assay for detecting Down syndrome were 95.4%, 100%, and 99.5%, respectively. Rapid prenatal diagnosis of Down syndrome using QF-PCR is a reliable technique that aids clinical management of pregnancy.

Fibroblast growth factor 21 (FGF21) is an important metabolic regulator expressed predominantly in the liver. In this study, we evaluated the role of LY2405319, an analogue of FGF21, in hepatic stellate cell (HSC) activation and in a methionine and choline-deficient (MCD)-diet induced mouse model of liver fibrosis. During liver injury, HSCs trans-differentiate into activated myofibroblasts which produce alpha-smooth muscle actin (α-SMA) and become a major cell type in hepatic fibrogenesis. Succinate and succinate receptor (GPR91) signaling has emerged as a regulator to promote α-SMA production in MCD diet- induced mice. Treatment with palmitate or MCD medium on LX-2 cells (HSCs) increased succinate concentration in the conditioned medium and cell lysate of LX-2 cells and increased production of GPR91 and α-SMA. However, LY2405319 administration ameliorates palmitate or MCD media-induced succinate production and decreases over-expression of GPR91 and α-SMA in LX2-cells. In an in vivo study, the MCD diet treatment caused increased steatohepatitis and liver fibrosis compared with the control diet in mice. Administration of LY2405319 improved steatohepatitis ameliorated GPR91 and α -SMA production in the liver, decreased succinate concentration in both liver and serum of MCD diet -induced mice. These results suggest that FGF21 reduces production of α-SMA by inhibiting the succinate-GPR91 pathway. We conclude that FGF21 acts as an inhibitor of the succinate-GPR91 pathway to control liver fibrosis. This suggests that FGF21 has therapeutic potential for treating liver fibrogenesis.

We have previously demonstrated that repeated treatment with methamphetamine (MA) results in a recognition memory impairment via upregulation of protein kinase C (PKC) δ and downregulation of the glutathione peroxidase-1 (GPx-1)-dependent antioxidant system. We also demonstrated that far-infrared ray (FIR) attenuates acute restraint stress via induction of the GPx-1 gene. Herein, we investigated whether exposure to FIR modulates MA-induced recognition memory impairment in male mice, and whether cognitive potentials mediated by FIR require modulation of the PKCδ gene, extracellular signal-regulated kinase (ERK) 1/2, and glutathione-dependent system. Repeated treatment with MA significantly increased PKCδ expression and its phosphorylation out of PKC isoenzymes (i.e., PKCα, PKCβI, PKCβII, PKCζ, and PKCδ expression) in the prefrontal cortex of mice. Exposure to FIR significantly attenuated MA-induced increase in phospho-PKCδ and decrease in phospho-ERK 1/2. In addition, FIR further facilitated the nuclear factor E2-related factor 2 (Nrf2)-dependent glutathione synthetic system. Moreover, L-buthionine-(S, R)-sulfoximine, an inhibitor of glutathione synthesis, counteracted the FIR-mediated phospho-ERK 1/2 induction and memory-enhancing activity against MA insult. More important, positive effects of FIR are comparable to those of genetic depletion of PKCδ or the antipsychotic clozapine. Our results indicate that FIR protects against MA-induced memory impairment via activations of the Nrf2-dependent glutathione synthetic system, and ERK 1/2 signaling by inhibition of the PKCδ gene.

The aim of this study was to evaluate the association between maternal serum estriol levels, which are routinely measured in the first trimester of pregnancy, and adverse pregnancy outcomes including gestational diabetes. We performed a retrospective chart analysis of women who delivered between July 1, 2007, and December 31, 2009, at Kangnam CHA Medical Center in Seoul, Korea. Only patients with available estriol measurements during their pregnancies and complete follow-up data were included in the study. The effect of estriol on the incidence of adverse pregnancy outcomes was examined using multinomial logistic regression analysis with age and pre-pregnancy body mass index (BMI) as covariates. The total number of subjects was 1,553, the mean age was 32.9 ± 3.7 years, and the mean pre-pregnancy BMI was 21.2 ± 3.0 kg/m2. Unconjugated estriol > 95th percentile of the screened population or unconjugated estriol ≥ 2.0 MoM (Multiple of the Median) was significantly associated with an increased risk for developing gestational diabetes mellitus (GDM), after adjusting for age and pre-pregnancy maternal weight. High levels of unconjugated estriol in the maternal serum during the early second trimester of pregnancy are a useful predictor of GDM development.

Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro.

Carbohydrate microarrays have become robust and powerful tools for the rapid analysis of glycan-associated binding events. However, this microarray technology has rarely been applied in studies of glycan-mediated cellular responses. Herein we describe a carbohydrate microarray-based approach for the rapid screening of biologically active glycans that stimulate the production of reactive oxygen species (ROS) through binding to the cell-surface lectin. We employed a microarray assay and a fluorescent ROS probe to identify the functional glycans which enhance ROS production. Cells binding to glycans on the microarrays produced ROS, whose levels were decreased in the presence of a ROS scavenger or a NADPH oxidase inhibitor. The present study leads us to suggest that glycan microarrays are applicable to the simultaneous screening of various glycans whose binding to the cell-surface lectin elicits cellular response.