Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.

Background: Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. Methods: We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. Results: There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). Conclusions Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.

Objectives: The purpose of this study was to compare the fracture strength and traslucency of 3D printing resin crowns according to different thicknesses. Methods: Resin crowns were designed with CAD software and a 3D scanner, using scanned data of the #61 tooth model. Resin Crowns with different thicknesses were printed using a 3D printer, and subsequently divided into four groups according to thickness (0.3, 0.5, 0.7, and 1.0 mm). Fracture strength was compared among groups with a resin strip crown of 1.0 mm thickness. Compressive force was applied using a universal testing machine at 30° along the lingual surface at 1 mm/min cross head speed. For translucency evaluation, thin square specimens were printed of thicknesses 0.3, 0.5, 0.7, and 1.0 mm, and translucency was measured using a spectrophotometer. Results: As a result of fracture strength measurement, fracture strength increased as thickness increased, and a significant difference was observed solely between thicknesses of 0.3 and 0.5 mm, and the thicknesses of 0.3 and 0.5 mm (P<0.05). Translucency decreased as thickness increased, and similarly, a significant difference was observed only between thicknesses of 0.3 and 0.5 mm and the thicknesses of 0.7 and 1.0 mm (P<0.05). Conclusions A 3D printing resin crown can be used as a clinical option for restoring a primary anterior tooth affected by caries.

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.
Caenorhabditis elegans* ; Caenorhabditis* ; Eating ; Ethanol ; Ginger* ; Heat-Shock Proteins ; Humans ; Lipofuscin ; Longevity* ; Natural Resources ; Reactive Oxygen Species ; Reproduction ; Superoxide Dismutase ; Survival Rate

PURPOSE: The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. MATERIALS AND METHODS: Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables. RESULTS: Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. CONCLUSION: Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.
Aged* ; Breast Neoplasms* ; Breast* ; Follow-Up Studies ; Humans ; Korea* ; Methods ; Population Characteristics ; Prevalence ; Risk Factors ; Survival Rate ; Treatment Outcome

BACKGROUND/AIMS: Currently, the videofluoroscopic swallowing study (VFSS) is the standard tool for evaluating dysphagia. We evaluated whether the addition of endoscopist-directed flexible endoscopic evaluation of swallowing (FEES) to VFSS could improve the detection rates of penetration, aspiration, and pharyngeal residue, compared the diagnostic efficacy between VFSS and endoscopist-directed FEES and assessed the adverse events of the FEES. METHODS: In single tertiary referral center, a retrospective analysis of prospectively collected data was conducted. Fifty consecutive patients suspected of oropharyngeal dysphagia were enrolled in this study between January 2012 and July 2012. RESULTS: The agreement in the detection of penetration and aspiration between VFSS and FEES of viscous food (kappa=0.34; 95% confidence interval [CI], 0.15 to 0.53) and liquid food (kappa=0.22; 95% CI, 0.02 to 0.42) was "fair." The agreement in the detection of pharyngeal residue between the two tests was "substantial" with viscous food (kappa=0.63; 95% CI, 0.41 to 0.94) and "fair" with liquid food (kappa=0.37; 95% CI, 0.10 to 0.63). Adding FEES to VFSS significantly increased the detection rates of penetration, aspiration, and pharyngeal residue. No severe adverse events were noted during FEES, except for two cases of epistaxis, which stopped spontaneously without requiring any packing. CONCLUSIONS: This study demonstrated that the addition of endoscopist-directed FEES to VFSS increased the detection rates of penetration, aspiration, and pharyngeal residue.
Aged ; Deglutition/*physiology ; Deglutition Disorders/*diagnosis/radiography ; Female ; Fluoroscopy/methods ; Humans ; Laryngoscopy/*methods/statistics & numerical data ; Male ; Middle Aged ; *Pharynx/radiography ; Reproducibility of Results ; Retrospective Studies ; Video Recording

This is a report of the first South Korean case of a lung disease caused by Mycobacterium simiae. The patient was a previously healthy 52-year-old female. All serial isolates were identified as M. simiae by multi-locus sequencing analysis, based on hsp65, rpoB, 16S-23S rRNA internal transcribed spacer, and 16S rRNA fragments. A chest radiography revealed deterioration, and the follow-up sputum cultures were persistently positive, despite combination antibiotic treatment, including azithromycin, ethambutol, and rifampin. To the best of our knowledge, this is the first confirmed case of a lung disease caused by M. simiae in South Korea.
Azithromycin ; Bronchiectasis ; Ethambutol ; Female ; Follow-Up Studies ; Humans ; Korea* ; Lung Diseases* ; Lung* ; Middle Aged ; Mycobacterium* ; Nontuberculous Mycobacteria ; Radiography ; Rifampin ; Sputum ; Thorax

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.
Administration, Oral ; Animals ; Body Weight ; Dogs ; Rats ; Rats, Sprague-Dawley ; Rodentia ; Scutellaria ; Scutellaria baicalensis ; Toxicity Tests