Computational Approach to Identify Enzymes That Are Potential Therapeutic Candidates for Psoriasis

Psoriasis is well known as a chronic inflammatory dermatosis. The disease affects persons of all ages and is a burden worldwide. Psoriasis is associated with various diseases such as arthritis. The disease is characterized by well-demarcated lesions on the skin of the elbows and knees. Various genetic and environmental factors are related to the pathogenesis of psoriasis. In order to identify enzymes that are potential therapeutic targets for psoriasis, we utilized a computational approach, combining microarray analysis and protein interaction prediction. We found 6,437 genes (3,264 upregulated and 3,173 downregulated) that have significant differences in expression between regions with and without lesions in psoriasis patients. We identified potential candidates through protein-protein interaction predictions made using various protein interaction resources. By analyzing the hub protein of the networks with metrics such as degree and centrality, we detected 32 potential therapeutic candidates. After filtering these candidates through the ENZYME nomenclature database, we selected 5 enzymes: DNA helicase (RUVBL2), proteasome endopeptidase complex (PSMA2), nonspecific protein-tyrosine kinase (ZAP70), I-kappa-B kinase (IKBKE), and receptor protein-tyrosine kinase (EGFR). We adopted a computational approach to detect potential therapeutic targets; this approach may become an effective strategy for the discovery of new drug targets for psoriasis

Anti-apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro

Apoptosis and oxidative stress are essential for the pathogenesis of acute liver failure and fulminant hepatic failure. Human placental hydrolysate (hPH) has been reported to possess antioxidant and anti-inflammatory properties. In the present study, the protective effects of hPH against D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced hepatocyte apoptosis were investigated in vivo. In addition, the molecular mechanisms underlying the anti-apoptotic activities of hPH against D-GalN-induced cell death in vitro were examined. Male Sprague-D awley rats were injected with D-GaIN/LPS with or without the administration of hPH. Rats were sacrificed 24 h after D-GaIN/LPS intraperitoneal injection, and the blood and liver samples were collected for future inflammation and hepatotoxicity analyses. Changes in cell viability, apoptosis protein expression, mitochondrial mass, mitochondrial membrane potential, reactive oxygen species generation, and the levels of proteins and mRNA associated with a protective mechanism were determined in HepG2 cells pretreated with hPH for 2 h prior to D-GalN exposure. The findings suggested that hPH treatment effectively protected against D-GalN/LPS-induced hepatocyte apoptosis by reducing the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, interleukin-6, and tumor necrosis factor-α, and increasing the level of proliferating cell nuclear antigen. It was also found that hPH inhibited the apoptotic cell death induced by D-GalN. hPH activated the expression of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase, which were further upregulated by the Kelch-like ECH2-associated protein 1-p62-nuclear factor-erythroid 2-related factor 2 pathway, a component of oxidative stress defense mechanisms. Furthermore, hPH markedly reduced cytosolic and mitochondrial reactive oxygen species and rescued mitochondrial loss and dysfunction through the reduction of damage-regulated autophagy modulator, p53, and C/EBP homologous protein. Collectively, hPH exhibited a protective role in hepatocyte apoptosis by inhibiting oxidative stress and maintaining cell homeostasis. The underlying mechanisms may be associated with the inhibition of endoplasmic reticulum stress and minimization of the autophagy progress

Individualized diabetes nutrition education improves compliance with diet prescription

This study was designed to evaluate the effect of individualized diabetes nutrition education. The nutrition education program was open to all type 2 diabetes patients visiting the clinic center and finally 67 patients agreed to join the program. To compare with 67 education group subjects, 34 subjects were selected by medical record review. The education program consisted of one class session for 1-2 hours long in a small group of 4~5 patients. A meal planning using the food exchange system was provided according to the diet prescription and food habits of each subject. Measurements of clinical outcomes and dietary intakes were performed at baseline and 3 months after the education session. After 3 months, subjects in education group showed improvement in dietary behavior and food exchange knowledge. In education group, intakes of protein, calcium, phosphorus, vitamin B2, and folate per 1,000 kcal/day were significantly increased and cholesterol intake was significantly decreased. They also showed significant reductions in body weight, body mass index (BMI), and fasting blood concentrations of glucose (FBS), HbA1c, total cholesterol, and triglyceride. However, no such improvements were observed in control group. To evaluate telephone consultation effect, after the nutrition education session, 34 subjects of the 67 education group received telephone follow-up consultation once a month for 3 months. The others (33 subjects) had no further contact after the nutrition education session. Subjects in the telephone follow-up group showed a decrease in BMI, FBS, and HbA1c. Moreover, the subjects who did not receive telephone follow-up also showed significant decreases in BMI and FBS. These results indicated that our individually planned education program for one session was effective in rectifying dietary behavior problems and improving food exchange knowledge, and quality of diet, leading to an improvement in the clinical outcomes. In conclusion, our individualized nutrition education was effective in adherence to diet recommendation and in improving glycemic control and lipid concentrations, while follow-up by telephone helped to encourage the adherence to diet prescription

Interplay of Hydrogen Sulfide and Nitric Oxide on the Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

We studied whether nitric oxide (NO) and hydrogen sulfide (H2S) have an interaction on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of NO and H2S on pacemaker activities were investigated by using the whole-cell patch-clamp technique and intracellular Ca2+ analysis at 30℃ in cultured mouse ICC. Exogenously applied (±)-S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or sodium hydrogen sulfide (NaHS), a donor of H2S, showed no influence on pacemaker activity (potentials and currents) in ICC at low concentrations (10 µM SNAP and 100 µM NaHS), but SNAP or NaHS completely inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction at high concentrations (SNAP 100 µM and NaHS 1 mM). Co-treatment with 10 µM SNAP plus 100 µM NaHS also inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction. ODQ, a guanylate cyclase inhibitor, or glibenclamide, an ATP-sensitive K+ channel inhibitor, blocked the SNAP+NaHS-induced inhibition of pacemaker currents in ICC. Also, we found that SNAP+NaHS inhibited the spontaneous intracellular Ca2+ ([Ca2+]i) oscillations in cultured ICC. In conclusion, this study describes the enhanced inhibitory effects of NO plus H2S on ICC in the mouse small intestine. NO+H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca2+. These results may be evidence of a physiological interaction of NO and H2S in ICC for modulating gastrointestinal motility

The KIDSCREEN-52 Quality of Life Measure for Children and Adolescents (KIDSCREEN-52-HRQOL): Reliability and Validity of the Korean Version

The KIDSCREEN-52 quality-of-life (KIDSCREEN-52-HRQOL) is a relevant, worldwide tool used for assessing the health-related quality of life in children and adolescents. The purpose of this study was to define measurement properties of the Korean version of the KIDSCREEN-52 HRQOL. The original questionnaire was translated following international translation guidelines. Analysis regarding psychometric properties showed that the Cronbach-alpha ranged from 0.77 to 0.95. The correlation coefficient between the PedQL and KIDSCREEN-52 dimensions were high for the assessments of similar constructs. Therefore, the Korean version of the KIDSCREEN-52 was found to be suitable for use in Korean adolescents

Clinical characteristics of obese boys and girls in a high school: focused on abdominal fat indices, fatty liver and carotid intima-media thickness

PurposeOur study aimed to evaluated sex differences in clinical features of obese high school students.MethodsOne hundred three obese high school students (body mass index [BMI]≥85th percentile) and 51 control students (BMI<85th percentile) were enrolled in this study. Anthropometric measurements were performed. Fasting serum glucose, insulin, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and high-sensitive C-reactive protein were measured. Abdominal fat thickness, degree of fatty liver, and carotid intima-media thickness were measured by ultrasound.ResultsIn control and obese groups, waist circumference was significantly longer in boys but body fat mass was significantly higher in girls. In the control group, total cholesterol and LDL-C were higher in girls. In the obese group, however, aspartate aminotransferase, alanine aminotransferase and triglyceride were higher and HDL-C was lower in boys. Preperitoneal fat thickness was significantly higher in obese girls. In obese group, the degree of fatty liver was significantly higher in boys. Carotid intima-media thickness was not significantly different between boys and girls.ConclusionObese adolescents had distinguishable sex differences in body measurements, metabolic abnormalities, abdominal fat thickness and fatty liver. We can infer that these characteristics may extend into adult obesity