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Background Ruminococcus gnavus (R. gnavus) are mucin-degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment-induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD. Methods Four-week-old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated. Results Orally administered R. gnavus significantly reduced AD-associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA-specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2-related cytokine mRNA and upregulation of interleukin (IL)-10 and Foxp3 in the skin. The population of CD4+ FOXP3+ T cells in mesenteric- and skin-draining lymph nodes and butyrate levels in the cecum increased in R. gnavus-administered AD mice. Conclusions Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T-cell counts and short-chain fatty acids production in AD mice.

본 연구는 지역아동센터 서비스와 취약계층 청소년의 학교적응에 대한 통합적 이해를 도모하기 위해 양적연구와 질적연구의 상호보완을 목적으로 혼합연구를 실시하였다. 이를 위해 「지역아동센터아동패널」을 활용하여 양적연구를 실시하고, 지역아동센터를 이용하는 청소년의 심층 인터뷰를 토대로 질적 연구를 수행한 순차설명설계 방법으로 진행하였다. 혼합 연구 결과, 지역아동센터 서비스는 다양하고 복합적으로 취약계층 청소년의 학교적응에 긍정적 영향을 미쳤고, 자아탄력성의 간접효과가 나타났다. 한편, 지역아동센터 교사지지는 통계적으로 유의하지 않았으나 질적 연구에서 지역아동센터 교사지지 중요성은 강조되었다. 또한, 지역아동센터 내 프로그램화된 서비스만이 아닌 대상, 공간, 구조, 시스템 등을 통해 취약계층 청소년의 학교 적응에 순기능을 하고 있음이 드러났다. 이에 지역아동센터 서비스의 질적 강화와 교사의 전문성 강화 등 현장과 학계, 유관기관들을 통한 증거기반 결과물을 누적하여 취약계층 청소년의 학교적응 증진을 위해 다 체계적으로 노력해야 할 것이다.

Salmonella enterica infects a broad range of host animals, and zoonostic infection threatens both public health and the livestock and meat processing industries. Many antimicrobials have been developed to target Salmonella envelope that performs essential bacterial functions; however, there are very few analytical methods that can be used to validate the efficacy of these antimicrobials. In this study, to develop a potential biosensor for Salmonella envelope stress, we examined the transcription of the S. enterica serovar typhimurium spy gene, the ortholog of which in Escherichia coli encodes Spy (spheroplast protein y). Spy is a chaperone protein expressed and localized in the periplasm of E. coli during spheroplast formation, or by exposure to protein denaturing conditions. spy expression in S. typhimurium was examined by constructing a spy-gfp transcriptional fusion. S. typhimurium spy transcription was strongly induced during spheroplast formation, and also when exposed to membrane-disrupting agents, including ethanol and the antimicrobial peptide polymyxin B. Moreover, spy induction required the activity of regulator proteins BaeR and CpxR, which are part of the major envelope stress response systems BaeS/BaeR and CpxA/CpxR, respectively. Results suggest that monitoring spy transcription may be useful to determine whether a molecule particularly cause envelope stress in Salmonella.

Purpose Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether IL-17 variants and gut microbiota affect the development of AD in infancy. Methods Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis. Results In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17. Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or S. mitis-stimulated HIEC-6 cells. Conclusions These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.

This study investigated the effect of subconjunctival injections of bevacizumab, an anti-VEGF antibody, on processes involved in corneal wound healing after alkali burn injury. Mice were divided into three groups: Group 1 was the saline-treated control, group 2 received subconjunctival injection of bevacizumab 1 hr after injury and group 3 received bevacizumab 1 hr and 4 days after injury. Cornea neovascularization and opacity were observed using a slit lamp microscope. Corneal repair was assessed through histological analysis and immunostaining for CD31, alpha-SMA, collagen I, and TGF-beta2 7 days post-injury. In group 3, injection of bevacizumab significantly lowered neovascularization and improved corneal transparency. Immunostaining analysis demonstrated a reduction in CD31, alpha-SMA and TGF-beta2 levels in stroma compared to group 1. These results indicate that bevacizumab may be useful in reducing neovascularization and improving corneal transparency following corneal alkali burn injury by accelerating regeneration of the basement membrane.

PURPOSE The purpose of this study was to identify novel autoantigens that react with specific serum autoantibodies in patients with glaucoma. METHODS Sera from patients with glaucoma (n = 80) and healthy subjects without a known pathology (n = 20) were investigated by immunoblot performed with bovine optic nerve lysates and resolved by one- and two-dimensional electrophoresis. Proteins in the immunoreactive spots were selected and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) data analysis. All the sera from subjects were assayed using enzyme-linked immunosorbent assay to identify autoantibodies. RESULTS We selected two prominent bands with molecular weights of 100 and 220 kDa by 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and these two bands were only found in the glaucoma patients. Using one-dimensional electrophoresis and LC-MS/MS analyses, we identified these proteins to be valosin-containing protein (VCP) and fodrin, respectively, and using two-dimensional electrophoresis and LC-MS/MS analyses, VCP was identified to be a common target antigen. In patients with primary open angle glaucoma and normal tension glaucoma, the frequency of autoantibodies to recombinant human VCP was 42.0 and 23.3%, respectively (p < 0.002). In the enzyme-linked immunosorbent assay tests, autoantibody titers to recombinant human VCP were significantly higher than that in healthy controls (p < 0.025). CONCLUSIONS VCP represents a potential candidate target for autoantibodies on the optic nerve in patients with glaucoma.

This study investigated the effect of subconjunctival injections of bevacizumab, an anti-VEGF antibody, on processes involved in corneal wound healing after alkali burn injury. Mice were divided into three groups: Group 1 was the saline-treated control, group 2 received subconjunctival injection of bevacizumab 1 hr after injury and group 3 received bevacizumab 1 hr and 4 days after injury. Cornea neovascularization and opacity were observed using a slit lamp microscope. Corneal repair was assessed through histological analysis and immunostaining for CD31, alpha-SMA, collagen I, and TGF-beta2 7 days post-injury. In group 3, injection of bevacizumab significantly lowered neovascularization and improved corneal transparency. Immunostaining analysis demonstrated a reduction in CD31, alpha-SMA and TGF-beta2 levels in stroma compared to group 1. These results indicate that bevacizumab may be useful in reducing neovascularization and improving corneal transparency following corneal alkali burn injury by accelerating regeneration of the basement membrane.

Purpose: To study the effect of systemic administration of phenyl-N-tert-butylnitrone (PBN) on the degeneration of photoreceptor cells in rd mice. Methods: PBN was injected intraperitoneally into FVB/rd mice on postnatal days (P) 5 to 14 (group A), and P10 to 18 (group B). At days P14, 16, 18, 20 and 27, morphological changes and apoptosis were analyzed by staining with hematoxylin and eosin or DAPI. The effect of PBN on apoptosis was analyzed in retinal pigment epithelial (RPE) cells by the measurement of caspase-3 activity. Results: In control and group B mice, the outer nuclear layer (ONL) of the retina was composed of 8-10 rows at P12, and rapidly decreased to one row at P18. In group A mice, the ONL was preserved with 5-7 rows at P18, and decreased to one row at P22. PBN inhibited caspase-3 activity in cultured RPE cells. Conclusions: PBN delayed, but did not block, the degeneration of photoreceptor cells in rd mice. PBN may exert its inhibitory effect during the early phase of photoreceptor cell degeneration.

PURPOSE This study aimed to determine the relationship between the heat shock protein 70 from hsps70.1 and 70.3 on retinal photic injury after systemic hyperthermia. METHODS Eight-week-old female C57BU6 mice were kept at a constant temperature of 41-42 degrees C for 25-30 minutes. After dark-adaptation for 8 hours, intense light of 11000 lux was maintained for 6 hours. Histology and immunohistochemistry for the inducible heat shock protein 70 (hsp70), the constitutive heat shock protein 70 (hsc70), and westem blot analysis, reverse transcriptase-polymerase chain reaction for hsp70.1 and hsp70.3 were performed just before photic injury and after 1, 4, 7, and 14 days. RESULTS Light-induced retinal degeneration was prevented by thermotolerance. After hyperthermia, hsp70 was densely expressed in the inner segment of the photoreceptor layer on the photic injury. Hsp70 expression increased for 4 days after photic injury and slowly decreased thereafter. mRNA from hsp70.3 was induced earlier than that of hsp70.1. CONCLUSIONS Retinal photic injury was prevented by hyperthermia-induced hsp70. Hsp70 from hsp70.3 may be a rapid and short-lived responder, and that from hsp70.1 is a slower and more sustained responder. Hsp70 from hsp70.3 may be an initial retinal chaperone while hsp70 from hsp70.1 may be a sustained chaperone.

Third cranial nerve palsy is rare in neurocysticercosis and is usually caused by supratentorial or sub-arachnoid lesions with accompanying hydrocephalus or meningitis. We report a patient who presented with third cranial nerve palsy caused by neurocysticercosis involving the midbrain. The patient showed repeated exacerbation of symptoms on tapering corticosteroids. The experience with this patient indicates that tapering of corticosteroids should be performed very slowly in such cases.