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

Oral microbiome correlates with selected clinical biomarkers in individuals with no significant systemic disease

The oral microbiome is an important component of the microbiome in the human body. Although the association of the oral microbiome with various diseases, including periodontitis and cancer, has been reported, information on how the oral microbiome is related to health-related indicators in healthy populations is still insufficient. In this study, we examined the associations of the oral microbiome with 15 metabolic and 19 complete blood count (CBC)-based markers in 692 healthy Korean individuals. The richness of the oral microbiome was associated with four CBC markers and one metabolic marker. Compositional variation in the oral microbiome was significantly explained by four markers: fasting glucose, fasting insulin, white blood cell count, and total leukocyte count. Furthermore, we found that these biomarkers were associated with the relative abundances of numerous microbial genera, such as Treponema, TG5, and Tannerella. By identifying the relationship between the oral microbiome and clinical biomarkers in a healthy population, our study presents a direction for future studies on oral microbiome-based diagnosis and interventions

Transcription Factor Sp1 Is Involved in Expressional Regulation of Coxsackie and Adenovirus Receptor in Cancer Cells

Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (−503/−498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression

Chfr is linked to tumour metastasis through the downregulation of HDAC1

Chfr is a ubiquitin ligase that functions in the mitotic checkpoint by delaying entry into metaphase in response to mitotic stress. It has been suggested that Chfr is a tumour suppressor as Chfr is frequently silenced in human cancers. To better understand how Chfr activity relates to cell-cycle progression and tumorigenesis, we sought to identify Chfr-interacting proteins using affinity purification combined with mass spectrometry. Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Ectopic expression of Chfr in cancer cells that normally do not express it results in downregulation of HDAC1, leading to upregulation of the Cdk inhibitor p21^(CIP1/WAF1) and the metastasis suppressors KAI1 and E-cadherin. Coincident with these changes, cells arrest in the G1 phase of the cell cycle and become less invasive. Collectively, our data suggest that Chfr functions as a tumour suppressor by regulating HDAC1

Characteristics of children with trauma compared to those with disease in the emergency department: a Korean single regional emergency medical center study

Purpose Trauma is the leading cause of death and disability in children. We aimed to compare the clinical characteristics of children with trauma and disease. Methods We reviewed the medical records of children (< 19 years) who visited the emergency department of Pusan National University Hospital from 2016 through 2018. Data on the age, age group, sex, details of trauma or disease, severe trauma or disease (Korean Triage Acuity Scale 1-2), hospitalization rate (overall and intensive care unit [ICU]), hospital length of stay, in-hospital mortality, and the Injury Severity Score were compared between the children with trauma and those with disease. Results In a total of 10,205 children, 3,028 (29.7%) had trauma. The children with trauma were older than those with disease (median age, 78.5 months [interquartile range, 35.0-165.0] vs. 49.0 [16.0-120.0]; P < 0.001). Boys were more common in the former group than the latter (63.7% vs. 56.3%; P < 0.001). The most common injury mechanism was traffic accident (16.0%), followed by fall and foreign body. The overall hospitalization rate was higher in the children with disease (17.1% vs. 35.9%; P < 0.001). However, the children with trauma underwent more frequent ICU hospitalization, and showed higher in-hospital mortality rate and longer hospital length of stay than those with disease (all P < 0.001). The children with severe trauma showed higher median age, percentage of boys, in-hospital mortality, and ICU hospitalization rate, and longer hospital length of stay than those with severe disease (all P < 0.001). Conclusion Children with trauma tend to be older, and their condition may be more critical in severity than those with disease. This difference is more prominent in those with severe trauma or disease

Clinical features of children with carbon monoxide intoxication: a single center study

Purpose To investigate the effect of lifestyle changes on patterns of carbon monoxide (CO) exposure and the association between neurologic symptoms and outcomes in Korean children with CO intoxication. Methods We reviewed the medical records of patients (< 18 years) with CO intoxication who visited the emergency department of Pusan National University Hospital between February 2012 and January 2020. We collected clinical findings, including age and sex, transfer from other hospitals, source, time and duration of exposure, manifestations with neurologic symptoms (syncope, seizure, and altered mental status), intensive care unit hospitalization, hospital length of stay, implementation of hyperbaric oxygen therapy, and findings of neuroimaging. These variables were compared between children with and without neurologic symptoms. In addition, levels of carboxyhemoglobin and lactate were compared between patients with and without specific manifestations. Results The enrolled 47 patients’ median age was 10 years (interquartile range, 4.5-14.0). The most common source of exposure was fire (46.8%), followed by camping (23.4%). The most common times of exposure were night (44.7%) and winter (44.7%). The patients with neurologic symptoms (14 [29.8%]) showed longer duration of exposure and hospital length of stay (P < 0.001 and P = 0.007, respectively). Of the 14 patients, 2 were hospitalized to the intensive care unit without an in-hospital mortality. A significant association was found between dyspnea and lactate level (P = 0.049), also between syncope or presyncope and carboxy hemoglobin level (P = 0.017). Conclusion CO intoxication in Korean children is most often caused by fire and camping, and at night and in winter. There is a correlation between neurologic symptoms and duration of exposure to CO

Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day

The effect of hip abductor fatigue on static balance and gait parameters

Objective: Hip abductors play a role in providing stability and movement to the lower limbs. The purpose of this study was to examine the effects of hip abductor fatigue on static balance and gait in the general population. Design: One group pre-test post-test design. Methods: Thirteen university students in their twenties volunteered for the study and had underwent a functional assessment. To induce fatigue, the subjects were instructed to raise their dominant lower extremity up against a load of 50% of 1 repetition maximum while producing hip abduction in a side-lying position. Subjects were instructed to maintain an abduction speed of 30 repetitions per minute to induce fatigue. Muscle fatigue was considered to be established when subjects were unable to perform hip abduction three consecutive times along with the metronome. A post-test of balance and gait was performed immediately in order to prevent fatigue recovery. The center of pressure (COP) distance area was measured using the Zebris FDM-S Multifunction Force measuring plate. Gait performance was analyzed using the GAITRite. Results: The COP distance was increased after fatigue was induced. There was a significant increase in the standard deviation of the medio-lateral and antero-posteror distance (p&lt;0.05). Although there was no significant difference in gait parameters, there was a significant decrease in single support time after fatigue was induced (p&lt;0.05). Conclusions: There was an increase in static balance instability and a significant decrease in single support time during gait due to hip abductor muscle fatigue

The Effects of Acupuncture Stimulation for Brain Activation and Alcohol Abstinence Self-Efficacy: Functional MRI Study

We attempted to investigate whether acupuncture stimulation at HT7 can have an effect on brain activation patterns and alcohol abstinence self-efficacy. Thirty-four right-handed healthy subjects were recruited for this study. They were randomly assigned into two groups: the HT7 (Shenmen) group and the LI5 (Yangxi) group. Acupuncture stimulation was performed using a block paradigm during fMRI scanning. Additionally, the Korean version of Alcohol Abstinence Self-Efficacy Scale (AASES) was used to determine the effect of acupuncture stimulation on self-efficacy to abstain from alcohol use. According to the result of fMRI group analysis, the activation induced by HT7 stimulation was found on the bilateral postcentral gyrus, inferior parietal lobule, inferior frontal gyrus, claustrum, insula, and anterior lobe of the cerebellum, as well as on the left posterior lobe of the cerebellum (p<0.001, uncorrected). According to the AASES analysis, the interaction effect for gender and treatment was marginally significant (F(1,30)=4.152, p=0.050). For female group, the simple main effect of treatment was significant (F(1,11)=8.040, p=0.016), indicating that the mean change score was higher in the HT7 stimulation than in the LI5 stimulation. Therefore, our study has provided evidence to support that HT7 stimulation has a positive therapeutic effect on the alcohol-related diseases

KIOM-79, an Inhibitor of AGEs–Protein Cross-linking, Prevents Progression of Nephropathy in Zucker Diabetic Fatty Rats

Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications, including diabetic nephropathy. KIOM-79, an 80% ethanolic extract obtained from parched Puerariae Radix, gingered Magnolia Cortex, Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the development of renal disease in Zucker diabetic fatty rats, an animal model of type 2 diabetes. In vitro inhibitory effect of KIOM-79 on AGEs cross-linking was examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50 mg/kg/day) was given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood glucose, glycated hemoglobin, urinary albumin and creatinine excretions were monitored. Kidney histopathology, collagen accumulation, fibrinogen and transforming growth factor-beta 1 (TGF-β1) expression were also examined. KIOM-79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular degeneration, collagen deposition and podocyte apoptosis. In the renal cortex, TGF-β1, fibronectin mRNA and protein were significantly reduced by KIOM-79 treatment. KIOM-79 reduces AGEs accumulation in vivo, AGE–protein cross-linking and protein oxidation. KIOM-79 could be beneficial in preventing the progression of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs deposition in the glomeruli