Search

An immunoaffinity layer was constructed based on the outer membrane of streptococcal protein G autodisplaying E. coli cells to improve the sensitivity of immunoassays and biosensors by the orientation control of antibodies.

Purpose: This study aimed to conduct a scoping review of studies on interventions for the prevention of safety accidents involving infants. Methods: The scoping review method by Arksey and O'Malley was used to conduct an overview based on information spanning a wide range of fields. Multiple electronic databases, PubMed, CINAHL, RISS, and KISS, were searched for articles written in English or Korean published from 2012 to the present on safety accident prevention interventions. A total of 2,137 papers were found, and 20 papers were ultimately analyzed. Results: Most studies were conducted in the United States (55.0%) and in the medical field (45.0%), and most were experimental studies (35.0%). The results were organized across five categories: 1) preventive precautions, 2) characteristics of children's developmental stages, 3) encouraging voluntary participation, 4) continuity of interventions, and 5) teaching methods. Conclusion: Safety accident prevention interventions should cover the establishment of a safe home environment, include voluntary participation, and provide routine follow-up interventions. Additionally, practical training and teaching methods that incorporate feedback rather than a lectureoriented approach should be adopted.

This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver damage in rats. HepG2 cells were used as the experimental cells and divided into five groups: non-treated control (normal), alcohol-induced control (control), mixture of herbal extracts (FNP-B), FNP-C, and a commercial treatment of liver diseases (Livers®); inhibition of detoxification and alcohol-induced damage was confirmed in vivo. Blood alcohol and acetaldehyde concentration after alcohol consumption were measured in a timely manner; alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione (GSH), glutathione transferase (GST), and lactate dehydrogenase (LDH) levels were measured in the liver. FNP-C exhibited the highest effect. When FNP-C was administered to alcohol-induced animals, blood alcohol and acetaldehyde concentration decreased compared to FNP-B and Livers®. FNP-C reduced ADH levels and improved LDH, GSH, GST, and SOD levels. The FNP-C group was effective in preventing alcohol-induced hangovers and liver damage. Thus, FNP-C improves hangovers and increases antioxidant activity in an alcohol-induced model. Adding amino acids and vitamins to natural ingredients can potentially enhance the effect of improving hangovers.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid β plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aβ deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aβ burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

Supplementary figure legends

Supplementary Table S1: Immunohistochemical staining of Notch1-IC and HIPK2 in serial tissue arrays of 61 breast cancer samples. Supplementary Table S2: Semi-Quantitative analysis of Notch1-IC, phosphorylated Notch1-IC T2512, HIPK2, and Fbw7 expression in breast cancer tissues.

Description of additional methods and procedures used in the study.

Supplementary Figure 1: ADR suppresses Notch1 signaling. Supplementary Figure 2: ADR inhibits the transcriptional activity of Notch1 by inducing HIPK2. Supplementary Figure 3: HIPK2 regulates the Notch1-IC protein stability through proteasomal degradation pathways. Supplementary Figure 4: HIPK2 facilitates Notch1-IC degradation by Fbw7 ubiquitin ligase. Supplementary Figure 5: HIPK2 physically interacts with Notch1-IC. Supplementary Figure 6: HIPK2 phosphorylates Notch1-IC at the T2512 residue. Supplementary Figure 7: HIPK2-mediated downregulation of Notch1-IC suppresses the tumorigenesis of breast cancer. Supplementary Figure 8: Somatic mutations in the CPD motif of Notch1-IC make it resistant to HIPK2. Supplementary Figure 9: Physiological effects of somatic mutations in the CPD motif of Notch1-IC. Supplementary Figure 10: A propose model of Notch1 signaling pathway regulation by HIPK2 in cancer during chemotherapy.

The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728–40. ©2016 AACR.

Background: Alcohol consumption has been considered as a modifiable risk factor for dementia development and alcohol-related brain damage may further impair cognitive abilities in dementia patients. This study aimed to find out the differences in cognitive function according to current alcohol drinking in patients with self-perceived memory decline, including subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early Alzheimer-type dementia (ATD).Methods: From May 2018 to December 2019, retrospective chart review was performed in patients who visited CHA Bundang Medical Center for cognitive decline. A two-way analysis of variance with interaction test were used to analyze the impact of alcohol consumption on cognitive function between groups.Results: A total of 147 patients was classified into three groups of SCD (n=30), MCI (n=53), and ATD (n=64), and each group was divided into two subgroups of alcohol users and alcohol non-users, according to the current status of alcohol consumption. Between SCD, MCI and ATD groups, scores of clock drawing test and Go/No-go test were significantly lower in current alcohol users of ATD groups compared to the SCD and MCI groups (p

Liver cirrhosis is characterized by the extensive deposition of extracellular matrix such as fibril collagen, causing dysfunction and failure of the liver. Hepatic macrophages play pivotal roles in the transition from inflammatory to restorative properties upon hepatic injury. In particular, scar-associated macrophages (SAMacs) control liver fibrosis with the representative expression of matrix metalloproteinase (MMP). However, the heterogenic SAMac population has not been well characterized yet. Here, we profiled heterogeneous liver macrophages using public databases of single-cell transcriptomics and found TIM4

Background Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS., Graphical abstract Image 1

OBJECTIVE We aimed to identify a relation between the level of silica exposure and the associated increase in the risk of radiologic usual interstitial pneumonia (UIP) pattern. METHODS We selected data of 796 individuals with pneumoconiosis who had undergone a chest computed tomography (CT). We estimated the silica exposure by comparing their occupational history with the data silica dust exposure. RESULTS Individuals employed as stonemasons demonstrated a 2.30-fold increase in the risk of developing UIP than coal mine workers (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.04 to 5.07). The high silica exposure group was associated with a 2.23-fold increase in the risk of developing UIP than the low silica exposure group (OR, 2.23; 95% CI, 1.07 to 4.69). CONCLUSIONS This study suggests that silica exposure is associated with an increased risk of developing UIP pattern, highlighting a dose-response relationship.

G protein–coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma.

Enhancing adult neurogenesis in the brain has been suggested as a potential therapeutic for AD. We developed a screening platform ATRIVIEW® for molecules activating neuronal differentiation of adult mouse NSCs. Among FDA-approved drugs, the most potent hit was SNR1611 (trametinib), a selective MEK1/2 inhibitor. We found that trametinib increases the level of P15INK4b and Neurog2, suggesting a mechanism for how MEK1/2 inhibition induces neuronal differentiation. Oral administration of trametinib increased adult neurogenesis in the dentate gyrus and subventricular zone of the AD model mouse 5XFAD. Surprisingly, we also found that trametinib enhanced adult neurogenesis in the brain cortex. Consequently, trametinib rescued AD pathologies such as neuronal loss or cognitive impairment of 5XFAD mice. Finally, trametinib induced neurogenic differentiation of NSCs derived from AD patient iPSCs, which suggests its potential therapeutic application. Altogether, we suggest that restoration of endogenous adult neurogenesis by trametinib may be a promising therapeutic approach to AD.

BACKGROUND/OBJECTIVES A dietary restriction on the intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has been reported to be effective in the treatment of gastrointestinal (GI) tract complications. Enteral nutrition (EN) is widely used for patients who cannot obtain their nutritional requirements orally, but many studies have reported EN complications, especially diarrhea, in up to 50% of patients. SUBJECTS/METHODS We performed a single-center, non-randomized, controlled trial to determine the effects of a low-FODMAP enteral formula on GI complications in patients in intensive care units (ICUs). Patients in the ICU who needed EN (n = 66) were alternately assigned to the low-FODMAP group (n = 33) or the high-FODMAP group (n = 33). RESULTS Anthropometric and biochemical parameters were measured, and stool assessment was performed using King's Stool Chart. We excluded patients who received laxatives, GI motility agents, proton pump inhibitors, antifungal agents, and antibiotics other than β-lactams. There were no differences in GI symptoms during 7 days of intervention, including bowel sound, abdominal distension, and vomiting between the 2 groups. However, diarrhea was more frequent in the high-FODMAP group (7/33 patients) than the low-FODMAP group (1/33 patients) (P = 0.044). CONCLUSIONS Our results suggest that a low-FODMAP enteral formula may be a practical therapeutic approach for patients who exhibit enteral formula complications. Our study warrants further randomized clinical trials and multicenter trials. Trial Registration Clinical Research Information Service Identifier: KCT0005660.

Despite the increase in the number of cases among South Korean sanitation workers, lung cancer as a result of exposure to occupational carcinogen has not been sufficiently investigated. This study aimed to identify exposure levels of sanitation workers to respirable crystalline silica (RCS) for various tasks and factors that affect individual RCS exposure. Exposure to RCS was assessed for 90 sanitation workers from seven companies. The obtained geometric mean value of the RCS was 2.6 µg m–3, which is a similar level to recommendations set by California’s Office of Environmental Health Hazard Assessment's Recommended Exposure Limit. Meanwhile, coal briquette ash (CBA) collectors exhibited the highest RCS concentration (24 µg m–3), followed by road cleaning workers who used a blower, municipal household waste collectors, sweepers, and drivers (p

The purpose of this study was to propose an effective exercise program for improving healthy physical fitness by examining how the combination of vacuum breathing exercise affects lung function and exogenous stress in general men who participate in general weight t raining. Subjects were 28 general men in their 20s to 30s who participated in general weight t raining, divided into 14 G.G (General Group) subjects who only performed general weight training and 14 V.G (Vacuum Group) subjects who performed vacuum breathing exercises for 8 weeks. The research results are as follows. In lung function, there was no significant change in G.G, and there was a significant increase in V.G. In exogenous stress, G.G increased significantly, and V.G decreased significantly. The lung function of the two groups had a significant effect between the time*groups. Exogenous stress also had a significant effect between Time*Groups. Therefore, if only weight training was performed, lung function development was difficult and exogenous stress increased, but vacuum breathing exercise was effective in developing lung function and reducing exogenous stress. It is believed that the efficiency of aerobic metabolism increases with the development of lung function and acts as a factor to reduce exogenous stress applied to the body during exercise.

This study is the concept of home training for modern people who cannot exercise properly in the recent Corona 19 era. Unlike conventional BOSU balls, the handy mini BOSU Pods is easy to carry and can enjoy a variety of fun exercises by connecting nearby objects and maintenance pods regardless of any place indoors or outdoors. The purpose of this study was to see how it affects balance, vascular health, and risk factors for metabolic disease. Exercise consisted of 50 minutes per day 3 times a week for a total of 8 weeks. As a result, through the Bosu Pods exercise, unipedal standing (right) and (left) in the sense of balance increased in the exercise group, showing a significant difference in the measurement period, and there was an interaction effect between the measurement period and the groups. Closed eyes stand (right) and (left) also increased in the exercise group, showing a significant difference in the measurement period and group, and it was found that there was an interaction effect. Vascular health did not show any difference between the timing and the group, but it was found to have an interactive effect. Metabolic disease risk factors decreased in body weight and body fat percentage, showing a significant difference, and it was found that there was an interaction effect only in body fat percentage, and only waist circumference, fasting blood sugar, and TG decreased at the time of measurement, showing a significant difference. There were no statistically significant changes in vascular health, systolic, diastolic blood pressure, and HDL-C. Taken together from the above results, BOSU Pods exercise is thought to be an exercise that can improve balance and improve vascular health and risk factors for metabolic diseases for obese women. Therefore, I think that if these exercises are programmed for a longer period of time, positive effects will appear physically and mentally in the era of Corona 19.

Anti-inflammatory therapies have been shown to be effective in the prevention of various cardiovascular diseases, tumors, and cancer complications. Thymoquinone (TQ), the main active constituent of Nigella sativa, has shown promising therapeutic properties in many in vivo and in vitro models. However, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone. Studies have explored the combination of TQ with biological nanomaterials to improve its bioavailability. The TQ nanoparticle formulation shows better bioavailability than free TQ, and these formulations are ready for clinical trials to determine their potential as therapeutic agents. In this paper, we review current knowledge about the interaction between TQ and the inflammatory response and summarize the research prospects in Korea and abroad. We discuss the different biological activities of TQ and various combination therapies of TQ and nanomaterials in clinical trials.

Inflammation is an immune response that protects against harmful stimuli. However, severe inflammation can cause many diseases, such as diabetes, cancer, and arthritis. In this study, we examined the anti-inflammatory efficacy and mechanism of Potentilla paradoxa Nutt. ethanol extract (Pp-EE) as a new strategy for controlling the inflammatory response. Cellular activities and the molecular target of Pp-EE were identified in RAW264.7 cells and HEK293T cells. The effect of Pp-EE was analyzed using the Griess assay, the luciferase assay, reverse transcription-polymerase chain reaction, and Western blotting. To evaluate the in vivo effects, an HCl/EtOH-induced gastritis mouse model was used. NO production and pro-inflammatory gene (iNOS, COX-2, and TNF-α) mRNA levels were decreased by Pp-EE in a concentration-dependent manner without showing cytotoxicity. The activation of the transcription factor, particularly NF-κB, was effectively suppressed by Pp-EE. It was also found that Pp-EE directly inhibits the activation of Src in lipopolysaccharide (LPS)-treated RAW264.7 cells and in Src-overexpressed HEK293 cells by Western blotting analysis and cellular thermal shift assay. Experiments in the gastritis mouse model indicated that Pp-EE suppresses HCl/EtOH-induced gastric lesions, the expression levels of COX-2, IL-6, and TNF-α, and the phosphorylation of p65, p50, and Src. Taken together, these results suggest that Pp-EE can be applied as an anti-inflammatory remedy with a Src/NF-κB inhibitory property.

본 연구는 실제 현장인 건물외부에 광촉매 코팅제, 광촉매 페인트, 광촉매 숏크리트를 적용함으로써 미세먼지의 원인물질인 NOx의 저감효과를 정량적으로 분석하였다. NOx 저감을 확인하기 위해 실험실 환경에서 ISO 22197-1에 의거하여 예비시험을 실시한 후, 실제 건물을 대상으로 현장실험을 측정 및 분석하였다. 예비시험을 통해 NO 저감량은 광촉매 코팅재 7.29 μmol/150 ㎠, 광촉매 페인트 5.76 μmol/150 ㎠, 숏크리트 11.28 μmol/150 ㎠로 나타났으며 이는 일본광촉매협회에서 정한 평가 기준인 1.5 μmol/150 ㎠ 이상인 것을 참고할 때 광촉매 외장재료 3개의 제품 모두 NO 제거성능이 기준치 이상임을 확인하였다. 실험실 측정과 현장실험의 실험 조건을 최대한 동일하게 설정하기 위해 UV 광량과 해당 광량에 대한 NO 주입량이라는 변수를 분석하였고, 현장 실험을 위한 광촉매 반응기를 자체 제작하였다. 현장의 UV 광량을 측정하고 이를 고려한 NO 주입량을 3 ppm으로 결정하였다. 현장 실험 결과, NO 제거량은 광촉매 코팅을 적용한 A건물은 11.06 μmol/150 ㎠, 광촉매 페인트를 도포한 B건물은 맑은 날에 10.03 μmol/150 ㎠, 흐린 날은 4.87 μmol/150 ㎠로 나타났다. 광촉매 숏크리트를 설치한 C건물에는 맑은 날에 6.78 μmol/150 ㎠, 흐린 날에 2.62 μmol/150 ㎠로 나타났다. 3개의 건물 모두 맑은 날 측정한 NO 제거량이 2배 이상 높게 나타났다. 실험실에서 측정한 예비시험의 NO 제거 성능에 비해 현장에서 측정한 NO 제거 성능이 높았고, A, B건물이 C건물에 비해 NO 제거 성능이 높게 나타났다. 이는 예비시험을 실시한 실험시 조건보다 UV 광량이 다소 높은 것에 기인한 것으로 판단된다. 광촉매 기술을 활용한 외장재를 실제 건물의 적용 시 주변건물과 환경조건을 고려하여 일조에 유리하게 외장재를 적용하여야 NO 저감을 극대화할 수 있다. 본 연구를 통해 실험실 조건에서 실시했던 ISO-22197-1 NO 제거 성능시험방법을 착안하여 실제 자연광 상태의 대기조건 하에서 건물에 적용해봄으로써, 실험실과 자연상태의 NO 제거성능을 비교하고 정량적으로 확인할 수 있었다. 향후 다양한 환경 조건의 실제 건물들에 적용하여 실험 결과의 객관성을 확보할 수 있는 연구를 수행할 계획이다.

In this study, we performed serial monitoring using targeted DNA sequencing to identify genetic alterations in adults with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL). Deep sequencing was performed by targeting the coding regions of 45 genes with recurrent driver mutations and 1129 single nucleotide polymorphism sites. Of the 43 patients that we examined, at least one case of genetic alterations was detected in 38 (88%) of the 43 patients at diagnosis (somatic mutations in 10 patients [23%] and copy number aberrations [CNA] in 36 patients [84%]). The most frequently detected CNA lesions were in

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease (COPD), and continuous CS exposure causes lung inflammation and deterioration. To investigate the protective effects of Artemisia gmelinii against lung inflammation in this study, cigarette smoke extract (CSE)/lipopolysaccharide (LPS)-treated alveolar macrophages (AMs) and mice stimulated with CSE/porcine pancreas elastase (PPE) were used. Artemisia gmelinii ethanol extract (AGE) was effective in decreasing the levels of cytokines, chemokine, inducible nitric oxide synthase, and cyclooxygenase-2 by inhibiting mitogen-activated protein (MAP) kinases/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in AMs. Additionally, oral administration of AGE suppressed inflammatory cells’ infiltration and secretion of inflammatory cytokines, chemokines, matrix metallopeptidase 9, and neutrophil extracellular traps in bronchoalveolar lavage fluid from the COPD model. Moreover, the obstruction of small airways, the destruction of the lung parenchyma, and expression of IL-6, TNF-α, IL-1β, and MIP-2 were suppressed by inhibiting NF-κB activation in the lung tissues of the AGE group. These effects are associated with scopolin, chlorogenic acid, hyperoside, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid, which are the main components of AGE. These data demonstrate the mitigation effect of AGE on lung inflammation via inhibition of MAPK and NF-κB pathways, suggesting that AGE may be instrumental in improving respiratory and lung health.