Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence.

Interleukin-10 Knockout Mice Do Not Reliably Exhibit Macroscopic Inflammation: A Natural History Endoscopic Surveillance Study.

BACKGROUND: Interleukin (IL)-10 knockout (KO) mice, a model for inflammatory bowel disease (IBD), develop chronic enterocolitis due to an aberrant immune response to enteric antigens. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models. AIMS: To assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies. METHODS: BALB/cJ IL-10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0-3 points each). An endoscopic score ≥ 1 point was considered as the presence of colitis/flare. RESULTS: IL-10 KO mice (N = 40, 9 female) were assessed. Mean age at first endoscopy was 62.5 ± 2.5 days; average number of procedures per mouse was 6.0 ± 1.3. A total of 238 endoscopies were conducted every 24.8 ± 8.3 days, corresponding to 124.1 ± 45.2 days of surveillance per mouse. Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5 ± 1.3 (range: 1-6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2-3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies. CONCLUSIONS: In this large-scale endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.

The Epidermal Environment's Influence on the Dermal Environment in Response to External Stress.

INTRODUCTION: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. METHODS: We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. RESULTS: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. CONCLUSION: Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.

Persicae Semen Promotes Bone Union in Rat Fractures by Stimulating Osteoblastogenesis through BMP-2 and Wnt Signaling.

Fractures cause extreme pain to patients and impair movement, thereby significantly reducing their quality of life. However, in fracture patients, movement of the fracture site is restricted through application of a cast, and they are reliant on conservative treatment through calcium intake. Persicae semen (PS) is the dried mature seeds of Prunus persica (L.) Batsch, and in this study the effects of PS on osteoblast differentiation and bone union promotion were investigated. The osteoblast-differentiation-promoting effect of PS was investigated through alizarin red S and Von Kossa staining, and the regulatory role of PS on BMP-2 (Bmp2) and Wnt (Wnt10b) signaling, representing a key mechanism, was demonstrated at the protein and mRNA levels. In addition, the bone-union-promoting effect of PS was investigated in rats with fractured femurs. The results of the cell experiments showed that PS promotes mineralization and upregulates RUNX2 through BMP-2 and Wnt signaling. PS induced the expression of various osteoblast genes, including Alpl, Bglap, and Ibsp. The results of animal experiments show that the PS group had improved bone union and upregulated expression of osteogenic genes. Overall, the results of this study suggest that PS can promote fracture recovery by upregulating osteoblast differentiation and bone formation, and thus can be considered a new therapeutic alternative for fracture patients.

Effect of Diminutive Adenoma with High-Grade Dysplasia on Surveillance Colonoscopy Interval.

BACKGROUND: Colonoscopy surveillance guidelines set the surveillance schedule based on polyp characteristics. Polyps with high-grade dysplasia (HGD) require 3 years of follow-up regardless of size. However, it is unclear whether patients with diminutive polyps (≤5 mm) with HGD have a higher risk. We evaluated the effect of diminutive adenoma with HGD on adenoma occurrence. METHODS: From January 2015 to December 2017, patients who underwent index and surveillance colonoscopy were retrospectively screened. The patients were grouped into no adenoma group, low-risk (patients with ≤2 low-grade dysplasia [LGD]), diminutive HGD, and high-risk (HGD >5 mm, ≥3 adenomas) groups according to the index colonoscopy results. Each group was analyzed using logistic analysis. RESULTS: The mean follow-up period was 22.47 months. Altogether, 610 (50.45%) patients had LGD and 152 (12.5%) had HGD. Among them, 61 (5.0%) patients had a diminutive polyp with HGD. Analysis of the risks of developing advanced adenoma in the surveillance colonoscopy showed that compared to the no adenoma group, the diminutive HGD group did not show a significant risk (odds ratio [OR] = 1.503 [0.449-5.027], p = 0.509), while the high-risk group showed a significant risk (OR = 2.044 [1.015-4.114], p = 0.045). CONCLUSIONS: Diminutive adenoma with HGD increased the risk of adenoma on surveillance colonoscopy, and in the case of advanced adenoma, the risk was increased, but it was not statistically significant.

Anti-obesity effects of medicinal plants from Asian countries and related molecular mechanisms: a review.

Medicinal plants have been used as an alternative medicine for obesity prevention, and Asian countries, which are major habitats of various medicinal plant species, have traditionally used these medicines for centuries. Obesity is a global health problem caused by excessive fat accumulation linked to abnormal lipid metabolism, such as adipogenesis, lipogenesis, and lipolysis. Accordingly, the effects of medicinal plants on obesity-related mechanisms and biomarkers have been evaluated in various experimental studies. For example, adipogenesis and lipogenesis are regulated by several transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and fatty acid synthase. Moreover, activation of the adenosine monophosphate-activated protein kinase pathway is accompanied by promotion of lipolysis. However, few reports have consolidated studies of the effects of various Asian medicinal plants on obesity and related mechanisms. Therefore, in this review, we examined the associations of medicinal plants originating from Asian countries with obesity and discussed the related mechanisms and biomarkers from in vitro and in vivo studies.

3,4-dihydroxytoluene, a metabolite of rutin, suppresses the progression of nonalcoholic fatty liver disease in mice by inhibiting p300 histone acetyltransferase activity.

3,3',4',5,7-Pentahydroxyflavone-3-rhamnoglucoside (rutin) is a flavonoid with a wide range of pharmacological activities. Dietary rutin is hardly absorbed because the microflora in the large intestine metabolize rutin into a variety of compounds including quercetin and phenol derivatives such as 3,4-dihydroxyphenolacetic acid (DHPAA), 3,4-dihydroxytoluene (DHT), 3,4-hydroxyphenylacetic acid (HPAA) and homovanillic acid (HVA). We examined the potential of rutin and its metabolites as novel histone acetyltransferase (HAT) inhibitors. DHPAA, HPAA and DHT at the concentration of 25 µM significantly inhibited in vitro HAT activity with DHT having the strongest inhibitory activity. Furthermore, DHT was shown to be a highly efficient inhibitor of p300 HAT activity, which corresponded with its high degree of inhibition on intracellular lipid accumulation in HepG2 cells. Docking simulation revealed that DHT was bound to the p300 catalytic pocket, bromodomain. Drug affinity responsive target stability (DARTS) analysis further supported the possibility of direct binding between DHT and p300. In HepG2 cells, DHT concentration-dependently abrogated p300-histone binding and induced hypoacetylation of histone subunits H3K9, H3K36, H4K8 and H4K16, eventually leading to the downregulation of lipogenesis-related genes and attenuating lipid accumulation. In ob/ob mice, administration of DHT (10, 20 mg/kg, iv, every other day for 6 weeks) dose-dependently improved the NAFLD pathogenic features including body weight, liver mass, fat mass, lipid accumulation in the liver, and biochemical blood parameters, accompanied by the decreased mRNA expression of lipogenic genes in the liver. Our results demonstrate that DHT, a novel p300 histone acetyltransferase inhibitor, may be a potential preventive or therapeutic agent for NAFLD.

Development and Validation of a Risk Scoring Model for Early Prediction of Severe Colon Ischemia.

BACKGROUND: Colon ischemia (CI) is injury to the intestines secondary to insufficient blood flow. Its clinical severity can range from mild to life-threatening. AIMS: To investigate predictive risk factors for CI and propose a scoring model for severe outcomes. METHODS: We retrospectively analyzed the medical records of patients admitted to Chungnam National University Hospital from January 2010 to December 2018. CI was defined as severe when patients required surgery immediately or after initial conservative management, death occurred after hospitalization, or symptoms persisted after 2 weeks. By controlling for possible confounders from the logistic regression analysis, we obtained a new risk scoring model for the early prediction of severe CI. Furthermore, using the area under the receiver operating characteristics curve (AUROC), we assessed the accuracy of the model. RESULTS: A total of 274 patients endoscopically diagnosed with CI were included, of whom 181 had severe CI. In the multivariate analysis, tachycardia, elevated C-reactive protein, Favier endoscopic classification stage ≥ 2, and history of hypertension were independently and significantly associated with severe CI. The AUROC of the model was 0.749. CONCLUSIONS: This risk scoring model based on the presence of tachycardia, elevated C-reactive protein level, unfavorable endoscopic findings by Favier's classification, and the history of hypertension could be used to predict severe CI outcomes at an early stage.

Comparison of conventional and modified endoscopic mucosal resection methods for the treatment of rectal neuroendocrine tumors.

BACKGROUND/AIM: Small rectal neuroendocrine tumors (NETs) confined to the submucosa are endoscopically resectable. Because most rectal NETs are submucosal tumors, conventional endoscopic mucosal resection (cEMR) may not result in a complete resection. This study investigated whether modified EMRs, namely endoscopic submucosal resection with ligation (ESMR-L), EMR with precutting (EMR-P), and strip biopsy are superior to cEMR for achieving histologically complete resection (HCR) of rectal NETs. METHODS: Medical records of 215 patients who were treated with endoscopic resections for rectal NETs between January 2011 and July 2019 were retrospectively enrolled. Of the patients, 110, 33, 29, and 43 underwent cEMR, ESMR-L, EMR-P, and strip biopsy, respectively. For each method, HCR and en bloc resection rates, procedure times, and complication rates were measured. RESULTS: HCR was achieved with cEMR, EMR-P, ESMR-L, and strip biopsies for 74.5%, 90.9%, 93.1%, and 90.7% of cases, respectively. The HCR rate for cEMR was inferior to those of the modified EMRs (p = 0.045 for cEMR vs. EMR-P; p = 0.031 for cEMR vs. ESMR-L; p = 0.027 for cEMR vs. strip biopsy). Among the three modified EMRs, there was no significant difference in achieving HCR (p = 1.000). En bloc resection (p = 0.096) and complication rates (p = 0.071) were not significantly different among the four EMR methods, although EMR-P required the longest procedure time (p = 0.000). CONCLUSIONS: All three modified EMRs are superior to cEMR and are equally effective for achieving HCR of rectal NETs.

Discovery of Orphan Olfactory Receptor 6M1 as a New Anticancer Target in MCF-7 Cells by a Combination of Surface Plasmon Resonance-Based and Cell-Based Systems.

Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.

MicroRNAs and Calcium Signaling in Heart Disease.

In hearts, calcium (Ca2+) signaling is a crucial regulatory mechanism of muscle contraction and electrical signals that determine heart rhythm and control cell growth. Ca2+ signals must be tightly controlled for a healthy heart, and the impairment of Ca2+ handling proteins is a key hallmark of heart disease. The discovery of microRNA (miRNAs) as a new class of gene regulators has greatly expanded our understanding of the controlling module of cardiac Ca2+ cycling. Furthermore, many studies have explored the involvement of miRNAs in heart diseases. In this review, we aim to summarize cardiac Ca2+ signaling and Ca2+-related miRNAs in pathological conditions, including cardiac hypertrophy, heart failure, myocardial infarction, and atrial fibrillation. We also discuss the therapeutic potential of Ca2+-related miRNAs as a new target for the treatment of heart diseases.

Piceatannol reduces resistance to statins in hypercholesterolemia by reducing PCSK9 expression through p300 acetyltransferase inhibition.

The purpose of this study was to investigate the role of piceatannol (PT) in statin (rosuvastatin and simvastatin) resistance and tolerance and its association with PCSK9 expression via its p300 inhibitory (p300i) activity. An in vitro study was performed using HepG2 cells that were exposed to statins (rosuvastatin or simvastatin) with or without PT in delipidated serum (DLPS) medium. In the statin exposed conditions, PCSK9 expression was reduced following PT treatment when compared to HepG2 cells w/o PT treatment. Furthermore, no significant difference was observed in the expression of the transcription factors SREBP2 and HNF1α, which regulate PCSK9 expression. This resulted in low density lipoprotein receptor (LDLR) stabilization and reduced cellular cholesterol levels. This indicates that PT epigenetically controls statin-induced PCSK9 expression. Interestingly, PT attenuated p300 histone acetyltransferase (HAT) activity. Moreover, simulation of PT-p300 binding suggested that PT inhibits p300 as PT could be docked in the p300 HAT domain. Furthermore, inhibition of p300 HAT activity using C-646, a selective p300 inhibitor, or through an siRNA system effectively reduced PCSK9 induction upon statin exposure in HepG2 cells. The chromatin immunoprecipitation (ChIP) assays revealed that PT blocked the recruitment of p300 to the PCSK9 promoter region. In summary, PT attenuated statin-induced PCSK9 expression by inhibiting p300 HAT activity. Finally, co-administration of simvastatin and PT for 10 weeks further reduced plasma low-density lipoprotein-cholesterol (LDL-C) levels and stabilized the hepatic LDLR protein level compared with those resulting from single treatment of simvastatin in a high-fat diet-induced hypercholesterolemia mouse model. Our findings indicate that PT is a new nutraceutical candidate to reduce the statin resistance and tolerance that occurs in patients with hypercholesterolemia.

Analysis of factors associated with local recurrence after endoscopic resection of gastric epithelial dysplasia: a retrospective study.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used techniques for the treatment of gastric epithelial dysplasia. Previous studies have compared the clinical outcome of endoscopic resection for early gastric cancer, but few studies have focused on gastric dysplasia alone. This study aimed to evaluate the long-term prognosis following endoscopic procedures for gastric epithelial dysplasia, investigate differences in local recurrence rates according to the treatment modality, and identify risk factors associated with local recurrence. METHODS: In this retrospective study, local recurrence rates and risk factors associated with local recurrence were compared between 599 patients who underwent EMR and 306 who underwent ESD for gastric epithelial dysplasia from January 2011 to December 2015. RESULTS: The en bloc resection rate (32.2% vs. 100%, p < 0.001) and complete resection rate (94.8% vs. 99.0%, p = 0.003) were significantly lower in the EMR group than in the ESD group. The local recurrence rate was significantly lower in the ESD group (1.3%) than in the EMR group (4.2%; p = 0.026). There was a significantly increased risk of local recurrence, regardless of lesion location or histologic grade, in patients with lesions > 2 cm (p = 0.002) or red in color (p = 0.03). The ESD group had a significantly lower local recurrence rate, with a higher complete resection rate, than that in the EMR group (p < 0.05). In the case of recurrence after endoscopic resection, most of the recurred lesions were removed through additional endoscopic procedures; there was no difference between the two groups (p = 0.153). CONCLUSIONS: The complete resection rate was significantly higher, and the local recurrence rate was significantly lower, in patients with gastric epithelial dysplasia treated with ESD. Therefore, ESD should be considered the preferred treatment in patients with lesions > 2 cm or showing redness due to an increased risk of local recurrence and EMR may be possible for low-grade dysplasia that is less than 2 cm without surface changes such as redness, depression and nodularity.

Non-steroidal anti-inflammatory drug-induced enteropathy as a major risk factor for small bowel bleeding: a retrospective study.

BACKGROUND: Small bowel (SB) bleeding accounts for 5% of all gastrointestinal (GI) bleeding cases and 80% of obscure GI bleeding cases. Although angioectasia is the common etiology of SB bleeding, nonsteroidal anti-inflammatory drug (NSAID)-induced SB lesions are also reported as a major cause in studies from Eastern countries. Herein, we assessed the frequency of occurrence of NSAID-induced SB lesions in Korean patients with obscure GI bleeding. METHODS: We retrospectively analyzed medical records of all consecutive patients aged ≥18 years who underwent capsule endoscopy from March 2018 to February 2019 at Ulsan University Hospital and Kosin University Gospel Hospital. RESULTS: Of the 83 subjects (all Korean; mean age ± standard deviation: 59 ± 18 years; age range: 18-84 years; men: n = 52; women: n = 31), 55 (66.2%) had stool with clear blood and 28 (33.8%) had normal stool with iron deficiency anemia. The detection rate of SB bleeding and lesions using capsule endoscopy was 72.3% (60 of 83 patients). A significantly higher frequency (40 of 51) of ulcerative/erosive lesions than other causes was observed in patients with inactive bleeding but visible SB lesions. As a result, NSAID-induced enteropathy accounted for 30.1% of 83 patients with obscure GI bleeding (25 of the all 60 SB bleeding cases). CONCLUSIONS: Contrary to what is reported for patients in Western countries, this study in Korean patients showed an improved diagnostic yield of capsule endoscopy for obscure GI bleeding and that NSAID-induced enteropathy was the most common etiology of SB bleeding. Aggressive small intestine examination is required for patients with unexplained GI bleeding.

Validation of a new risk score system for non-variceal upper gastrointestinal bleeding.

BACKGROUND: Recently, a new international bleeding score was developed to predict 30-day hospital mortality in patients with upper gastrointestinal bleeding (UGIB). However, the efficacy of this newly developed scoring system has not been extensively investigated. We aimed to validate a new scoring system for predicting 30-day mortality in patients with non-variceal UGIB and determine whether a higher score is associated with re-bleeding, length of hospital stay, and endoscopic failure. METHODS: A retrospective study was performed on 905 patients with acute non-variceal UGIB who were examined in our hospital between January 2013 and December 2017. Baseline characteristics, endoscopic findings, re-bleeding, admission, and mortality were reviewed. The 30-day mortality rate of the new international bleeding risk score was calculated using the receiver operating characteristic curves and compared to the pre-endoscopy Rockall score, AIMS65, Glasgow Blatchford score, and Progetto Nazionale Emorragia Digestiva score. To verify the variable for the 30-day mortality of the new scoring system, we performed multivariate logistic regression using our data and further analyzed the score items. RESULTS: The new international bleeding scoring system showed higher receiver operating characteristic (ROC) curve values in predicting mortality (area under ROC curve 0.958; [95% confidence interval (CI)]), compared with such as AIMS65 (AUROC, 0.832; 95%CI, 0.806-0.856; P < 0.001), PNED (AUROC, 0.865; 95%CI, 0.841-0.886; P < 0.001), Pre-RS (AUROC, 0.802; 95%CI, 0.774-0.827; P < 0.001), and GBS (AUROC, 0.765; 95%CI, 0.736-0.793; P < 0.001). Multivariate analysis was performed using our data and showed that the 30-day mortality rate was related to multiple comorbidities, blood urea nitrogen, creatinine, albumin, syncope at first visit, and endoscopic failure within 24 h during the first admission. In addition, in the high-score group, relatively long hospital stay, re-bleeding, and endoscopic failure were observed. CONCLUSION: This is a preliminary report of a new bleeding score which may predict 30-day mortality better than the other scoring systems. High-risk patients could be screened using this new scoring system to predict 30-day mortality. The use of this scoring system seemed to improve the outcomes of non-variceal UGIB patients in this study, through proper management and intervention.

Subepithelial Spread of Early Gastric Signet Ring Cell Carcinoma: How Far They Can Reach?

INTRODUCTION: Although signet ring cell carcinoma (SRC) is a poorly differentiated cancer subtype, recent studies suggest that endoscopic resection can be applied in small, mucosal early gastric SRC. However, other studies report frequent positive lines at the lateral resection margin after endoscopic treatment. Subepithelial spread beneath normal mucosa can exist in SRC, and such lesions may be the cause of positive margins after endoscopic resection. Thus, we conducted a retrospective study in order to evaluate the significance of subepithelial spread in early gastric SRC. METHOD: Medical records of early gastric SRC patients who underwent surgery or endoscopic resection from January 2011 to December 2016 at a single tertiary hospital (Daejeon, South Korea) were reviewed to examine subepithelial spread and clinical datum. Two expert pathologists reviewed all pathologic specimens, and only patients showing a pure SRC component were included. RESULTS: Eighty-six patients were initially enrolled, and subepithelial spread existed in 62 patients (72.1%). The mean distance of subepithelial spread was 1,132.1 µm, and the maximal distance was 6,000 µm. Only discoloration was significantly associated with the presence of a subepithelial spread (p < 0.05, χ2 test, and logistic regression test). Distance of subepithelial spread did not correlate with total lesion size. CONCLUSION: Subepithelial spread of early gastric SRC occurs frequently and can reach up to 6 mm. Lesion discoloration may be associated with the presence of subepithelial spread. Our results suggest that careful decision of the margin is needed when performing endoscopic resection of early gastric SRC.

Quality of Preoperative Colonoscopy Affects Missed Postoperative Adenoma Detection in Colorectal Cancer Patients.

BACKGROUND: Despite thorough preoperative screening, 19-30% of synchronous polyps or adenomas are detected after colon cancer surgery. Remnant synchronous lesions require additional colonoscopy procedures or surgery. AIM: To investigate factors of preoperative colonoscopy potentially affecting the detection of missed lesions in patients subjected to colorectal cancer surgery. METHODS: Of 1147 colorectal cancer patients subjected to curative open or laparoscopic colectomy and colonoscopy at the Chungnam National University Hospital from January 2012 to December 2016, 518 patients underwent pre- and postoperative colonoscopy. The index colonoscopy was defined as the last preoperative endoscopy performed. We analyzed pre- and postoperative medical charts for colonoscopy and pathological data. The effects of patient, procedure, and tumor factors on the postoperative adenoma detection rate, advanced adenoma detection rate, and adenoma miss rate (AMR) were analyzed. RESULTS: The overall AMR was 25.7% (95% confidence interval, 22.2-29.8%). Comparing optimal and non-optimal bowel preparation groups, the latter had greater postoperative polyp missed rate (PMR), AMR (p < 0.01), and AAMR (p = 0.272). The optimal preparation group allowed identification of more synchronous adenomas than in the fair (OR 5.72) and poor (OR 11.39) preparation groups. On univariate analysis, patient age and left-sided colectomy (p < 0.01) influenced AMR. Multivariate analysis showed that age, preoperative bowel preparation, and left colon resection influenced postoperative AMR. CONCLUSION: A better quality of index colonoscopy had a positive effect on lowering the detection rate of postoperative adenoma. Older age and suboptimal bowel preparation at the index colonoscopy and left-sided colectomy had negative effects on lowering the postoperative AMR.

Anti-inflammatory effect of Vaccinium oldhamii stems through inhibition of NF-κB and MAPK/ATF2 signaling activation in LPS-stimulated RAW264.7 cells.

BACKGROUND: Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. METHODS: Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. RESULTS: Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. CONCLUSIONS: These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

Consumption of black food decreases the risk of abdominal obesity in Korean women.

BACKGROUND AND OBJECTIVES: The association between black-colored foods (black foods) such as black beans, known for their high antioxidant capacity, and the prevention of metabolic diseases has been explored, but not in a large population. Therefore, this study examined relationships between the consumption of black foods and metabolic syndrome in Korean adults. METHODS AND STUDY DESIGN: Data from 9,499 40-65-year old subjects (3,675 men and 5,824 women) from the 2010-2015 Korea National Health and Nutrition Examination Survey were used in the analysis. Black food consumption was estimated using 24-h dietary recall data, and analyses were performed according to black food consumer and non-consumer groups. RESULTS: The average total consumption of black foods was higher in women than men. The total black food consumer group in women had a 24% reduced risk of abdominal obesity than the non-consumer group (p=0.007). Furthermore, waist circumference decreased significantly with an increase in total black food consumption in women. High consumption of total black foods and black beans reduced the risk of abdominal obesity by 26% (p for trend=0.012) and 29% (p for trend=0.003) compared with no consumption. No risk factors for metabolic syndrome were associated with black food consumption in men. CONCLUSIONS: In conclusion, black foods, including black beans, may have beneficial effects on metabolic syndrome components, especially abdominal obesity.