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Author(s): Yizhi Liu [1]; David Granet [2]; Haotian Lin [1]; Sally Baxter [2]; Hong Ouyang [1]; Jie Zhu [2]; Shan Huang [1]; Zhenzhen Liu [1]; Xiaokang Wu [3]; Fangbing Yan [...]

To report the extensive dynamic clinical condition and long-term therapeutic prognosis in three cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome. Retrospective, interventional case series. Data of the three IRVAN syndrome patients were retrospectively reviewed at study enrollment and during the follow-up period. The mean follow-up time was 60 months. All three patients manifested the typical characteristics of IRVAN syndrome with bilateral eye involvement. The good long-term visual acuity has been maintained after treatment. The aneurysms showed extensive dynamic changes and regressed mostly. IRVAN syndrome is a rare condition that may progress rapidly and cause severe vision loss without treatment. The photocoagulation is beneficial and should be performed in the early phase. The aneurysms presented extensive dynamic changes through multimodal imaging which suggested a migratory inflammatory process involving retinal arterioles. [ABSTRACT FROM AUTHOR]

The anti‐inflammatory activity of cirsilineol in in vivo condition was assessed by measuring the relative organ weight, lung dry/wet weight ratio, protein concentration, and infiltration of inflammatory cells in bronchoalveolar lavage fluid. We estimated the myeloperoxidase activity and levels of cytokines, chemokines, and inflammatory markers to analyze the efficacy of cirsilineol against lipopolysaccharide (LPS)‐induced lung inflammation. Furthermore, we quantified the gene expression of NFkB/IKK signaling molecules in cirsilineol‐treated and untreated acute lung injury mice to confirm the anti‐inflammatory property of cirsilineol. The lung histology was assessed with hematoxylin and eosin staining. Apart from in vivo experiments, in vitro tests with LPS‐stimulated RAW 264.7 macrophages were also performed. Cell viability assay was performed in the presence and absence of LPS in RAW 264.7 macrophages to determine the cytotoxic effect of cirsilineol against macrophages. Reverse‐transcription polymerase chain reaction (RT‐PCR) analysis was done to analyze the gene expression of inflammatory markers in LPS‐treated RAW 264.7 macrophages to prove that cirsilineol effectively inhibits inflammation in vitro. The results of our study prove that cirsilineol effectively inhibits inflammation in both in vivo and in vitro conditions. RT‐PCR analysis results of NFkB/IKK signaling molecules clearly illustrate that cirsilineol inhibited the expression of NFkB/IKK signaling protein and thereby prevented inflammation in in vivo condition, and it is further confirmed with the results of inflammatory protein expression in vitro model. The lung histopathological studies authentically confirm that cirsilineol potentially prevented the mice from LPS‐induced lung inflammation. [ABSTRACT FROM AUTHOR]

Objective: Diabetic retinopathy, a common complication of diabetes mellitus and a major cause of blindness. circRNAs spongs target miRNA and thus influencing mRNA expression in DR. We investigated the mechanism of circ_001209 in regulating diabetic retinal vascular dysfunction.Methods: QRT-PCR analysis was performed to detect the expression of miR-15b-5p, COL12A1 and circ_001209 in human retinal vascular endothelial cells (HRVECs) under high glucose conditions. Western blot assay, wound healing assay, transwell assay and tube formation were used to explore the roles of circ_001209/miR-15b-5p/COL12A1 in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, RNA-FISH, and overexpression assays were performed to reveal the mechanisms of the circ_001209/miR-15b-5p/COL12A1 interaction. TUNEL staining and H&E staining were used to evaluate the pathological changes in streptozotocin (STZ)-induced DR in rats.Results: Downregulation of miR-15b-5p under HG conditions promoted proliferation, migration, and tube formation of HRVECs. QRT-PCR and western blot results revealed that miR-15b-5p affected the HRVECs function through targeting COL12A1. Under HG conditions, circ_001209, which acts as a sponge of miR-15b-5p, is upregulated. Besides, overexpression of circ_001209 can affect HRVEC function and aggravate retinal injury in diabetic rats.Conclusion: Upregulation of circ_001209 contributes to vascular dysfunction in diabetic retinas through regulating miR-15b-5p and COL12A1, providing a potential treatment strategy for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

The electromagnetic mechanism (EM) induced by localised surface plasma resonance (LSPR) and the charge transfer mechanism (CT) between adsorbed molecules and the substrate is generally believed to explain the overall effect of surface‐enhanced Raman spectroscopy (SERS). In some cases, the high complexity of the SERS system makes it difficult to identify the enhancement mechanism. In this paper, the synthesised MoO3 with excellent stability, uniformity and versatility is used to study the SERS of several dye molecules and fully clarify the mechanism. The SERS enhancement mechanism is explained mainly by the SERS behaviour of molecules at different wavelengths. This discovery is very helpful for future SERS substrate and mechanism research. [ABSTRACT FROM AUTHOR]

Abstract Background Stem cell transplantation as therapy for hematological disorders is often hampered by severe graft-versus-host-disease. This may be reduced by umbilical cord blood transplantation, an effect that has been attributed to qualitative differences between neonatal and adult T cells. We compared levels of secreted proteins and cytokine mRNA induced in cord blood leukocytes (CBL) and adult blood leukocytes (ABL) by various stimuli. Results While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-γ in CBL. Production of the Th2 cytokines IL-4, IL-5, and IL-13 and the hematopoietic cytokine IL-3 was much lower in CBL versus ABL after T-cell receptor-mediated stimulation, whereas production of GM-CSF was comparable in the 2 cell types. The lower levels of Th1 and Th2 cytokines were maintained in CBL during a 4-day time-course study, while after 12 hours IL-3 and GM-CSF reached in CBL levels similar to those in ABL. For all cytokines except IFNγ, the IC50 values for inhibition by cyclosporin A were similar in ABL and CBL. In contrast, there was less expression and activation of transcription factors in CBL. Activation of NF-κB by TPA/ionomycin was detected in ABL but not CBL. Furthermore, there was less expression of the Th subset-specific transcription factors T-bet and c-maf in CBL versus ABL, whereas GATA-3 expression was similar. Expression of T-bet and c-maf correlated with expression of the Th1 and Th2 cytokines, respectively. Time course experiments revealed that T-bet expression was stimulated in both cell types, whereas c-maf and GATA-3 were induced only in ABL. Conclusion The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-κB, whereas differences in Th subsets are due to differences in regulation of Th lineage-specific transcriptions factors. We propose that the reduced incidence and severity of GvHD after allogeneic transplantation of umbilical CB cells is due to lesser activation of specific transcription factors and a subsequent reduction in production of certain cytokines.

Quasipaa boulengeri is consumed as a valuable delicacy in many places in the world. Recent studies showed that water temperature is a very important environmental factor that influences the growth and metamorphosis of reared frog tadpoles. However, the molecular mechanisms of tadpoles in response to water temperature are still unknown. In this study, physiological changes and transcriptomes of tadpoles reared under different water temperatures were analyzed. The results showed that the body length, width, weight, and growth hormone content of tadpoles under 21°C were significantly higher than of those reared at 15°C or 27°C, indicating that frog tadpoles were highly sensitive to water temperature. Further comparative transcriptome analysis of these three groups of tadpoles identified a total of 2001 differentially expressed genes, which were predominantly related to energy metabolism and growth revealed by GO and KEGG enrichment. Importantly, in the GH/IGF signaling pathway, several key genes, including PI3K, ERK1/2, and AMPK, were expressed significantly differently among the three groups, and the expression levels coincided with the changes of phenotype and hormone level. Together, our study provided a suitable rearing temperature (21°C) for tadpoles and contributed to the knowledge of molecular mechanisms underlying tadpoles in response to rearing temperature. [ABSTRACT FROM AUTHOR]

Introduction: Intraocular foreign bodies (IOFBs) are a serious subset of open-globe injury that can result in visual loss. This study analyzed the epidemiology, clinical characteristics, and visual outcomes of patients with IOFBs in Southwest China. Methods: This retrospective study comprised 1,176 patients with the primary diagnosis of IOFBs who resided in Sichuan Province over a 10-year period. All data were collected from medical records and analyzed statistically. Results: The annual incidence for IOFBs was 0.14 per 100,000 (95% confidence interval 0.12–0.16 per 100,000) people in Southwest China. In that period, IOFBs accounted for 22.3% of all open-globe injuries. Working-age male patients accounted for 79.1% of all IOFBs patients and there had significant differences in age distributions between genders (p < 0.001). Metallic IOFBs were the most common (74.6%) IOFB, but there were significant differences in the materials of IOFBs between adults and children of different age-groups (p < 0.001). At discharge, 277 (23.6%) patients had increased visual acuity (VA) and 95 (8.0%) had no light perception. Initial VA <20/200 (odds ratio [OR], 5.5; p < 0.001), increasing wound size (OR, 1.3; p = 0.004), IOFBs in the posterior segment (OR, 2.6; p = 0.002) and existing complications (traumatic cataract, endophthalmitis, retinal detachment, or retinal break) were independent risk factors for final VA <20/200. Conclusion: The incidence of IOFBs in Southwest China differed from global statistics. Adults and children had different clinical characteristics. Thus, their prevention strategies should be different. [ABSTRACT FROM AUTHOR]

Abstract Background T cells play a dominant role in the pathogenesis of asthma. Costimulation of T cells is necessary to fully activate them. An inducible costimulator (ICOS) of T cells is predominantly expressed on Th2 cells. Therefore, interference of signaling pathways precipitated by ICOS may present new therapeutic options for Th2 dominated diseases such as asthma. However, these signaling pathways are poorly characterized in vitro and in vivo. Methods Human primary CD4+ T cells from blood were activated by beads with defined combinations of surface receptor stimulating antibodies and costimulatory receptor ligands. Real-time RT-PCR was used for measuring the production of cytokines from activated T cells. Activation of mitogen activated protein kinase (MAPK) signaling pathways leading to cytokine synthesis were investigated by western blot analysis and by specific inhibitors. The effect of inhibitors in vivo was tested in a murine asthma model of late phase eosinophilia. Lung inflammation was assessed by differential cell count of the bronchoalveolar lavage, determination of serum IgE and lung histology. Results We showed in vitro that ICOS and CD28 are stimulatory members of an expanding family of co-receptors, whereas PD1 ligands failed to co-stimulate T cells. ICOS and CD28 activated different MAPK signaling cascades necessary for cytokine activation. By means of specific inhibitors we showed that p38 and ERK act downstream of CD28 and that ERK and JNK act downstream of ICOS leading to the induction of various T cell derived cytokines. Using a murine asthma model of late phase eosinophilia, we demonstrated that the ERK inhibitor U0126 and the JNK inhibitor SP600125 inhibited lung inflammation in vivo. This inhibition correlated with the inhibition of Th2 cytokines in the BAL fluid. Despite acting on different signaling cascades, we could not detect synergistic action of any combination of MAPK inhibitors. In contrast, we found that the p38 inhibitor SB203580 antagonizes the action of the ERK inhibitor U0126 in vitro and in vivo. Conclusion These results demonstrate that the MAPKs ERK and JNK may be suitable targets for anti-inflammatory therapy of asthma, whereas inhibition of p38 seems to be an unlikely target.