Recent advances in ocular graft-versus-host disease

Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment

Automatic Lumen Segmentation in Intravascular Optical Coherence Tomography Images Using Level Set

<p> Automatic lumen segmentation from intravascular optical coherence tomography (IVOCT) images is an important and fundamental work for diagnosis and treatment of coronary artery disease. However, it is a very challenging task due to irregular lumen caused by unstable plaque and bifurcation vessel, guide wire shadow, and blood artifacts. To address these problems, this paper presents a novel automatic level set based segmentation algorithm which is very competent for irregular lumen challenge. Before applying the level set model, a narrow image smooth filter is proposed to reduce the effect of artifacts and prevent the leakage of level set meanwhile. Moreover, a divide-and-conquer strategy is proposed to deal with the guide wire shadow. With our proposed method, the influence of irregular lumen, guide wire shadow, and blood artifacts can be appreciably reduced. Finally, the experimental results showed that the proposed method is robust and accurate by evaluating 880 images from 5 different patients and the average DSC value was 98.1% +/- 1.1%.</p

Combination of Maternal Serum ESM-1 and PLGF with Uterine Artery Doppler PI for Predicting Preeclampsia

Objective: This study aimed to determine whether the combination of pregnancy-associated endothelial cell-specific molecule 1 (ESM-1), the placental growth factor (PLGF) in the first- and second-trimester maternal serum, and the uterine artery Doppler pulsatility index (PI) in the second trimester can predict preeclampsia (PE). Methods: The serum levels of ESM-1 and PLGF in 33 severe preeclampsia (SPE) patients, 18 mild preeclampsia patients (MPE), and 60 age-matched normal controls (CON) were measured. The Doppler ultrasonography was performed, and the artery pulsatility index (PI) was calculated for the same subjects. Results: The 2nd PLGF level was significantly lower and the 2nd PI was higher than those in the MPE group. Combining the 2nd PLGF with the 2nd PI yielded an AUC of 0.819 (83.33% sensitivity and 70.00% specificity). In the SPE group, the 1st ESM-1 level and the 2nd PLGF level were significantly lower, and the 2nd ESM-1 level and the 2nd PI were significantly higher in the SPE group. The combination of the 1st ESM-1, the 2nd PLGF, and the 2nd PI yielded an AUC of 0.912 (72.73% sensitivity and 95.00% specificity). Conclusions: The 1st ESM-1 and the 2nd PLGF levels and the 2nd PI were associated with PE. The combination of serum biomarkers and the PI improved the screening efficiency of the PE prediction, especially for SPE

Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response

Abstract: Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6-/- mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis

Galphai1 and Galphai3 regulate macrophage polarization by forming a complex containing CD14 and Gab1

Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincidedwith decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.Fil: Li, Xiaolin. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Duowei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Chen, Zen. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Lu, Ermei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Zhuo. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Duan, Jingjing. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Tian, Wei. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Wang, Yun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: You, Linjun. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zou, Yulian. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Cheng, Yan. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Zhu, Qingyi. Jiangsu Province Hospital of Traditional Chinese Medicine. Departament of Urology; ChinaFil: Wan, Xiaojian. Second Military Medical University. Department of Anesthesiology and Intensive Care Medicine, Changhai Hospita; ChinaFil: Xia, Tao. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; ChinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences. Laboratory of Neurobiology, ; Estados UnidosFil: Yang, Yong. China Pharmaceutical University. Center for New Drug Safety Evaluation and Research; Chin