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Exosomes are extracellular vesicles, 50-150 nm in diameter, released by most cells. Exosomes contain several intracellular components, including DNA, RNA, and proteins, which reflect the parent cell's status and contribute to intercellular communication. Cancers are associated with high morbidity and mortality rates worldwide. Owing to a high survival rate, cancer treatment by immune modulation of the tumor microenvironment has recently received a lot of attention. Exosomes' role in immunological control is also being studied extensively. Exosomes play a role in cancer-immune cell communication. Through intracellular communication, exosomes promote tumor growth, metastasis, angiogenesis, and drug resistance. In addition, innate immune cell-derived exosomes and adaptive immune cell exosomes have an anti-tumorigenic activity. Exosome-related tumor microenvironment drugs are being developed, including inhibitors of exosomal release, tumor-derived exosomes, and immune cell-derived exosome engineering, although there are still some obstacles to overcome. We describe in this review the significance of exosomes in the tumor microenvironment. We also summarize current studies on anticancer immune drug development and the challenges in developing exosome-related drugs.

Knowledge of the impact of the gut microbiota on human health has increased, and modulation of the bacterial community is now considered a therapeutic target for various diseases. Certain novel bacterial species have probiotic properties associated with improvement in obesity and related metabolic disorders. The relative abundance of Butyricimonas spp. is correlated with metabolic parameters; however, the physiological role of Butyricimonas in metabolic improvement is unclear. In this study, live and heat-killed Butyricimonas virosa were administered to mice with high-fat diet (HFD)-induced obesity. Both live and heat-killed B. virosa ameliorated HFD-impaired body weight, serum glucose level, insulin resistance, and liver steatosis. Moreover, activation of the glucagon-like peptide-1 receptor (GLP-1R) and peroxisome proliferator-activated receptor α (PPARα) was observed in the liver, and the expression levels of insulin receptor substrate (IRS)-1, IRS-2, Toll-like receptor 5 (TLR5), and zonula occludens-1 (ZO-1) were upregulated in the ileum. Finally, we demonstrated that the effect of B. virosa treatment on glucose regulation may be linked to the upregulation of GLP-1R in the liver and is not a result of colonization of the gut by B. virosa or B. virosa-produced butyrate. Our results provide a rationale for the development of Butyricimonas spp.-based therapeutics and prophylactics for hyperglycemia.

Supplemental Material for A Review and Meta-Analysis of Interactive Metronome Training: Positive Effects for Motor Functioning by Hyo Keun Lee, Hyun Joon Kim, Sang Bum Kim, and Nyeonju Kang in Perceptual and Motor Skills

Additional file 1. Results of sensitive analysis for variables.

Glycyl-tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20-58nm (mean diameter: 36.9nm) and a buoyant density of 1.13-1.17g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1-containing EVs (GARS1-EVs). Among the identified factors, insulin-like growth factor II receptor, and vimentin also contributed to the anti-cancer activity of GARS1-EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis.

본 연구는 도덕교육에 신경과학이 도입된 배경을 살피고, 신경과학 배후의 철학적 패러다임이 `물리주의`와 `환원주의`임을 밝히는 동시에 `이론적 검역`이 왜 필요한지 논변한다. 또한 신경과학적 사실로부터 규범적 결론을 도출하려는 시도가 지닌 한계 및 문제점을 확인하고, `신경 도덕교육` 이론의 개요와 그 한계를 고찰하며, 신경과학이 도덕교육에 유포시킬 수 있는 `신경 무의미`와 `개념적 오류`에 대해 진단한다. 이러한 논의를 통해 본 연구는 결론적으로 신경과학이 도덕교육의 희망이 되기 위해서는 도덕이 지닌 고유하고 풍부한 의미를 가르치는 도덕교육의 본령을 신경과학에게 내어주어서는 안 된다는 점을 강조하고자 한다.

Additional file 1: Figure S1. Surface localization of Epi-GV fusion protein. (A) Diagram of Epi-GV construct with C-terminal Strep tag (Epi-GV-strep). (B) Epi-GV-strep construct (or MOCK) was transfected to 293F cells with a trace amount of EGFP cDNA as a transfection marker, and its surface expression was analyzed by flow cytometry. Representative dot plots are shown. Figure S2. PMA-induced nuclear localization of epithin/PRSS14 intracellular domain. (A) 427 cells were transfected with two siRNAs against epithin/PRSS14, starved for serum, and stimulated with PMA or not. Cells were then stained with anti-N antibody (green) and DAPI (blue). Representative images are shown. Scale bars, 20 μm. (B) The computational method for determining EICD-positive pixels is illustrated. If the mean fluorescence of a particular pixel and the 8 pixels surrounding it in the nuclear image is greater than the threshold described in Methods section, the pixel was considered as an EICD-positive pixel. (C) Representative anti-N antibody-stained original image and binary image with epithin/PRSS14 positive pixels indicated in white are shown. (D) In the experiment described in A, normalized EICD nuclear localization (the sum of the fluorescence intensity of EICD-positive pixels in each cell divided by the mean fluorescence of nuclear region of the cell) was calculated and represented as bar graph. At least 57 cells from three microscopic fields were used for each condition. The error bar indicates SEM. ****p

Background Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer’s disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation. Methods To determine the effects of CA140 on the neuroinflammatory response, BV2 microglial cells were pretreated with lipopolysaccharide (LPS, 1 μg/mL), followed by treatment with CA140 (10 μM) and analysis by reverse transcription-polymerase chain reaction (RT-PCR). To examine whether CA140 alters the neuroinflammatory response in vivo, wild-type mice were injected with both LPS (10 mg/kg, intraperitoneally (i.p.)) and CA140 (30 mg/kg, i.p.), and immunohistochemistry was performed. In addition, familial AD (5xFAD) mice were injected with CA140 or vehicle daily for 2 weeks and examined for microglial and astrocyte activation. Results Pre- or post-treatment with CA140 differentially regulated proinflammatory responses in LPS-stimulated microglia and astrocytes. Interestingly, CA140 regulated D1R levels to alter LPS-induced proinflammatory responses. CA140 significantly downregulated LPS-induced phosphorylation of ERK and STAT3 in BV2 microglia cells. In addition, CA140-injected wild-type mice exhibited significantly decreased LPS-induced microglial and astrocyte activation. Moreover, CA140-injected 5xFAD mice exhibited significantly reduced microglial and astrocyte activation. Conclusions CA140 may be beneficial for preventing and treating neuroinflammatory-related diseases, including AD. Electronic supplementary material The online version of this article (10.1186/s12974-018-1321-3) contains supplementary material, which is available to authorized users.

Previous work by Kim, et al. (2017) unveiled that lysyl-tRNA synthetase (KRS) is secreted through a mechanism involving syntenin-containing exosomes. They described how KRS, commonly known as part of the translational machinery in the cytoplasm, is secreted into the extracellular space where it induces inflammation. First, KRS secretion is triggered by starvation conditions. The increase in caspase-8 levels during starvation is responsible for proteolysis and generation of the N-terminal truncated form of KRS, and this event is required for KRS dissociation from the multi-synthetase complex (MSC). N-terminal cleavage of KRS eventually leads to a conformational change that allows its interaction with the C-terminal PDZ binding motif of syntenin and subsequent exosome biogenesis. The KRS-syntenin complex translocates to multivesicular bodies (MVBs) that originate from endosomes involved with intraluminal vesicle (ILVs). MVBs are transporters for the secretion of cellular contents into the extracellular space. Syntenin localizes intraluminal vesicles within endosomal membranes. The KRS-syntenin complex transfers on to intraluminal vesicles in MVBs. MVBs are translocated to the plasma membrane for ILV secretion mediated by Rab family proteins. Once KRS exosomes are secreted, their membranes are eventually ruptured by proteases and KRS is released from the exosomes where it can act as an inflammatory cytokine in the extracellular space. Secreted KRS triggers macrophage/neutrophil migration and induces inflammation.

Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.

Neonatal leukemia, which develops in first 4 weeks of life, is a rare group of hematologic neoplasm with various symptoms and prognosis. In rare cases, obstructive jaundice can be shown as initial presentation. Therefore, it is often misdiagnosed as cholestatic liver diseases. We report a case of neonatal leukemia with obstructive jaundice which was misdiagnosed as biliary atresia. This case was diagnosed with bone marrow aspirates at the age of 14th day, and the result was given that about 93% of the cells were lymphoblasts.

본 연구는 항공사 객실승무원의 감정노동, 직무스트레스와 피로관리, 직무만족간의 영향관계를 규명하고자 하였다. 연구대상은 K항공사 객실승무원을 대상으로 연구를 수행한 결과 감정노동은 직무스트레스와 피로관리에는 긍정적인 영향관계를 나타났으며, 직무만족에는 표면적 감정노동만이 대부분 부정적으로 나타났으며, 이직의도에는 긍정적으로 나타났다. 또한, 성과스트레스와 동료스트레스는 직무만족에 부정적으로 나타났으며, 이직의도에는 긍정적으로 나타났다. 직무스트레스는 피로관리를 높이는 것으로 나타났으며, 피로관리와 직무만족간의 관계는 부정적으로 나타나 기존의 연구를 지지하는 것으로 나타났다. 하지만, 내면적 감정노동과 업무스트레스는 업무만족이나 충성도, 성과보상만족과 유의한 결과가 나타나지 않았으며, 정신적 피로도 성과보상에는 유의한 영향을 미치지 못하는 것으로 나타났다. 본 연구를 통해서 객실승무원의 감정노동, 직무스트레스, 피로관리, 직무만족의 관계를 규명함으로서 다른 관광관련 산업분야의 직원과의 차이점을 살펴볼 수 있었으며, LCC항공사 승무원 및 타 외국계 항공사 승무원을 대상으로 하는 관련 후속연구도 기대한다.

The major countries of Organization for Economic Cooperation and Development (OECD) have been promoting the Rural Development Policies for practical application of valuable resources in rural area since 1990th. They have been trying to change their agricultural industry policy from the Agricultural Policies, which promotes an intensive agriculture, an endogenous rural development, which promotes the Rural Development Policies, after the Doha Development Agenda (DDA) and the Free Trade Agreement (FTA) reinforcement. After 1960th in Korea, we focused on urban amenity and agriculture productivity. We had strived to do living environments, Agricultural Infrastructure, and Agricultural buildings for rural area developing; therefore, we obtained good results. However, our policy had been inclined too heavily toward beneficial urban type, so that we hadn’t been able to give meticulous care about rural resources, consideration of environment, and organized development. We accordingly require systematically discovering and developing the rural resources for the rural area’s develop competitive power as a basically settlement area. Political interest is increased in the Rural Amenity for Rural Development, off-farm Income. The Rural Amenity is presented, as the Rural Development Policies, in those interpretations for a solution of Rural Development and off-farm Income.

Purpose The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. Results The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). Conclusion Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.