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2篇 您的检索式:作者名="Denis Kaili"
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1Diabetes inhibits corneal epithelial cell migration and tight junction formation in mice and human via increasing ROS and impairing Akt signaling显示文摘Corneal wounds usually heal quickly;but diabetic patients have more fragile corneas and experience delayed and painful healing. In the present study, we compared the healing capacity of corneal epithelial cells (CECs) between normal and diabetic conditions and the potential mechanisms. Primary murine CEC derived from wild-type and diabetic (db/db) mice, as well as primary human CEC were prepared. Human CEC were exposed to high glucose (30 mM) to mimic diabetic conditions. Cell migration and proliferation were assessed using Scratch test and MTT assays, respectively. Reactive oxygen species (ROS) production in the cells was measured using dichlorofluorescein reagent. Western blot was used to evaluate the expression levels of Akt. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) expression were used to determine tight junction integrity. We found that the diabetic CEC displayed significantly slower cell proliferation and migration compared with the normal CEC from both mice and humans. Furthermore, ROS production was markedly increased in CEC grown under diabetic conditions. Treatment with an antioxidant N-acetyl cysteine (NAC, 100 μM) significantly decreased ROS production and increased wound healing in diabetic CEC. Barrier function was significantly reduced in both diabetic mouse and human CEC, while NAC treatment mitigated these effects. We further showed that Akt signaling was impaired in diabetic CEC, which was partially improved by NAC treatment. These results show that diabetic conditions lead to delayed wound-healing capacity of CEC and impaired tight junction formation in both mice and human. Increased ROS production and inhibited Akt signaling may contribute to this outcome, implicating these as potential targets for treating corneal wounds in diabetic patients.Qi-wei Jiang Denis Kaili Jonaye Freeman Chong-yang Lei Bing-chuan Geng Tao Tan Jian-feng He Zhi Shi Jian-jie Ma Yan-hong Luo Heather Chandler Hua Zhu 2019Acta Pharmacologica Sinica2019,40,9:8
2Biomarkers for response to immune checkpoint inhibitors in gastrointestinal cancers显示文摘Gastrointestinal(GI)cancers account for a large proportion of cancer deaths worldwide and pose a major public health challenge.Immunotherapy is considered to be one of the prominent and successful approaches in cancer treatment in recent years.Among them,immune checkpoint inhibitor(ICI)therapy,has received widespread attention,and many clinical findings support the feasibility of ICIs,with sustained responses and significantly prolonged lifespan observed in a wide range of tumors.However,patients treated with ICIs have not fully benefited,and therefore,the identification and development of biomarkers for predicting ICI treatment response have received further attention and exploration.From tumor genome to molecular interactions in the tumor microenvironment,and further expanding to circulating biomarkers and patient characteristics,the exploration of biomarkers is evolving with high-throughput sequencing as well as bioinformatics.More large-scale prospective and specific studies are needed to explore biomarkers in GI cancers.In this review,we summarize the known biomarkers used in ICI therapy for GI tumors.In addition,some ICI biomarkers applied to other tumors are included to provide insights and further validation for GI tumors.Moreover,we present single-cell analysis and machine learning approaches that have emerged in recent years.Although there are no clear applications yet,it can be expected that these techniques will play an important role in the application of biomarker prediction.Meng Li Denis Kaili Lei Shi 2022World Journal of Gastrointestinal Oncology2022,14,1:1
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