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Immunoregulatory and Anti-cancer Activities of Combination treatment of Novel Four-Herb Formula and Doxorubicin in 4t1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-man Hon HUang Dan-qi miranda sin-man t.ang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective to investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(tNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4t1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4t1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).the D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).the treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(Ptered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(Ption treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

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Cellular & Molecular Immunology 2020年第6期17卷 631-646页

作者： Xiaoyu Sun tianheng Hou Edwin Cheung tiffany Nga-teng Iu Victor Wai-Hou tam Ida Miu-ting Chu miranda sin-man t.ang Paul Kay-Sheung Chan Christopher Wai-Kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Cancer Centre/Centre of Precision Medicine Research and training Faculty of Health SciencesUniversity of MacaoMacaoChina Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Microbiology The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We elucidated the anti-inflammatory mechanisms of IL-38 in allergic *** bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly(I:C)/LyoVec or infection-related cytokine tNF-αto induce expression of cytokines/chemokines/adhesion *** dust mite(HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in ***-38 significantly inhibited induced proinflammatory IL-6,IL-1β,CCL5,and CXCL10 production,and antiviral interferon-βand intercellular adhesion molecule-1 expression in the coculture *** cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular StAt1,StAt3,p38 MAPK,ERK1/2,and NF-κB pathways,and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene *** injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the th2-related cytokines IL-4,IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)and lung *** examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia,together with reduced th2,th17,and innate lymphoid type 2 cell numbers but increased proportions of regulatory t cells in the lungs,spleen,and lymph ***-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice,together with significantly decreased CCR3^(+) eosinophil numbers in the BALF and lungs,and a reduced percentage of human CD4^(+)CRtH2^(+)th2 cells in the lungs and mediastinal lymph ***,our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic

关键词： allergic asthma eosinophils IL-38 ILC2s tregs

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Scavenger receptor BI: A multi-purpose player in cholesterol and steroid metabolism

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World Journal of Gastroenterology 2010年第47期16卷 591-5924页

作者： Menno Hoekstra theo JC Van Berkel miranda Van Eck Division of Biopharmaceutics Leiden/Amsterdam Center for Drug Research Gorlaeus Laboratories

Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. this review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a

关键词： Scavenger receptor class B type Ⅰ Highdensity lipoprotein Cholesterol Lipoprotein metabolism Liver Macrophages Adrenal gland Platelets Steroido- genesis

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PIGMENtED EPItHELIAL CYSt OF tHE IRIS

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中华医学杂志(英文版) 1934年第9期48卷 905-909页

作者： Y. t. t.ang Department of Ophthalmology Peiping Union Medical College Peiping.

Cyst of the iris seems to be a rare disease in China and no case has been so far reported anywhere in this country. In fact the following case is the first instance met with in this hospital since its opening in 1916. It is, therefore, thought of interest to report this case. A man patient, age 27, came to the Eve Clinic of the P.U.M.C. Hospital on October 3o, 1933, complaining of a "slowly growing black vesicle" in his left eye of over 2 months' duration. Past history. Over four months before, June 1933, patient had a sudden attack of "red eyes" associated with pain, lacrimation, photophobia, mucoia

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Correlation study of biological characteristics of non-small cell lung cancer A549 cells after transfecting plasmid by microbubble ultrasound contrast agent

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Asian Pacific Journal of tropical Medicine 2016年第6期9卷 564-567页

作者： Xuan-Yan Guo man-Lu Xue-Qing Chen Fan-Ding He ang-Li Ultrasonic Department Academy of Sciences of Sichuan Province People's Hospital of Sichuan Province Pancreatic Surgery West China Hospital Sichuan University

Objective: to explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA-224 and miRNA-122 a plasmids into nonsmall cell lung cancer A549 cells. Methods: Antisense miRNA-224 and miRNA-122 a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble mediated condition. We set up a control group. the cell proliferation activity, apoptosis, invasion ability were detected by Mtt assay, Annexin V-PE, transwell invasion experiment and colony formation assay, respectively. Results: the expression of mi RNA-224 decreased and the expression of miRNA-122 a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group(Pter the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122 a were inhibited, and the differences were significant as compared with the control group(P the inhibition of miRNA-122 a group was the most significant and there was statistically significant difference as compared with miRNA-224 group(t =-4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group(P t's more, the apoptotic peak appeared in miRNA-122 a group. Its invasion ability decreased most obviously(40.25 ± 3.97/visual field), the number of clone ability was 104.93 ± 4.87 and the inhibitory effect was the most obviously. there was statistically significant difference as compared with other groups(P transfected by ultrasound micro

关键词： Microbubble ultrasound contrast agent MiR-224 MiR-122a Non-small cell lung cancer

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利培酮与氟哌啶醇治疗抽动障碍有效性和安全性的Meta分析

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临床心身疾病杂志 2024年第2期30卷 18-24页

作者：马昂张耀东谷裕王梦琴赵小桐梅道启郑州大学附属儿童医院(河南省儿童医院) 河南郑州450018 郑州市儿童神经行为科学研究重点实验室河南郑州450018

目的系统评价利培酮与氟哌啶醇治疗抽动障碍的有效性和安全性。方法检索截至2023年8月在维普数据库、中国知网、万方医学数据库、PubMed、Embase和Cochrane Library发表的关于利培酮(观察组)与氟哌啶醇(对照组)治疗抽动障碍的随机对... 详细信息

目的系统评价利培酮与氟哌啶醇治疗抽动障碍的有效性和安全性。方法检索截至2023年8月在维普数据库、中国知网、万方医学数据库、PubMed、Embase和Cochrane Library发表的关于利培酮(观察组)与氟哌啶醇(对照组)治疗抽动障碍的随机对照试验,进行系统评价和Meta分析。2名研究人员利用Cochrane系统评价手册进行偏倚风险评估,使用Rev man 5.4软件进行数据分析。结果共纳入23篇研究,涉及1 599例患者。Meta分析显示,观察组患者治疗后不良反应症状量表评分及锥体外系反应、口干、嗜睡/镇静、静坐不能、便秘及体质量增加发生率均低于对照组(P0.05)。结论利培酮与氟哌啶醇均可有效治疗抽动障碍,改善患儿抽动症状,但利培酮的不良反应发生率较低,安全性更高。

关键词：利培酮氟哌啶醇抽动障碍有效性安全性 Meta分析

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth t.S.Mok Jing Wang Jingqing Li man Liu Wenshu tang Yu Feng Hector Kwong-Sang W ang Shun-Wa t.ang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai to Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

the liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer t(NKt)*** of PMN-MDSCs in CCRK transgenic mice restored NKt cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKt cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer t cell

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Li在单层tiSe2吸附与扩散的第一性原理研究

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兵器材料科学与工程 2023年第1期46卷 1-5页

作者：田瑞雪丁昂吴爱民张硕张贵锋姚曼黄昊大连理工大学材料科学与工程学院辽宁省能源材料及器件重点实验室辽宁大连116024 宁波星箭航天机械有限公司浙江宁波315153

通过密度泛函理论计算方法,研究Li在单层二硒化钛(tiSe2)的吸附与扩散行为,评估其用作锂离子电池电极材料的潜能。结果表明:Li吸附在单层tiSe2具有适宜的吸附能,且在t位点的吸附更稳定。Li在单层tiSe2的吸附过程使体系导电性提升,显示... 详细信息

通过密度泛函理论计算方法,研究Li在单层二硒化钛(tiSe2)的吸附与扩散行为,评估其用作锂离子电池电极材料的潜能。结果表明:Li吸附在单层tiSe2具有适宜的吸附能,且在t位点的吸附更稳定。Li在单层tiSe2的吸附过程使体系导电性提升,显示金属特性。差分电荷密度分析证明Li与tiSe2间主要是离子键。最后,计算得出Li在单层tiSe2的扩散能垒较低(0.23 eV),具有较高的速率性能。证明单层tiSe2有作为高性能锂离子电池负极材料的潜能。

关键词：锂离子电池电极材料 tiSe2 电子性质吸附和扩散密度泛函理论

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先天性糖基化异常Ik型的诊断学特征并文献复习

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中华诊断学电子杂志 2019年第4期7卷 249-253页

作者：王亚萍李荣培葛昂满宜刚济宁医学院临床医学院 272067 济宁市第一人民医院儿科 272011 青岛市妇女儿童医院儿科 266001

目的探讨先天性糖基化异常(CDG)-Ik型的诊断学特征。方法回顾性分析济宁市第一人民医院儿科于2018年6月7日收治的1例诊断为CDG-Ik型患儿的临床资料,分析其临床表现及基因检测结果并复习相关文献。结果男性患儿1岁,间断抽搐,双眼内斜,追... 详细信息

目的探讨先天性糖基化异常(CDG)-Ik型的诊断学特征。方法回顾性分析济宁市第一人民医院儿科于2018年6月7日收治的1例诊断为CDG-Ik型患儿的临床资料,分析其临床表现及基因检测结果并复习相关文献。结果男性患儿1岁,间断抽搐,双眼内斜,追视追听反应差,耳位偏低,双手无抓物意识,竖头不稳,运动发育落后,肌张力逐渐降低,膝腱反射减弱。检查发现肝功能异常,心肌损害,发育商低下。头颅磁共振成像(MRI)检查提示脑液腔隙较宽。基因测序全外显子检测,ALG1基因存在1处纯合突变:c.1312C>t(p.R438W),为错义突变,确诊为CDG-Ik型。经家系验证分析,受检人的父母该位点均为杂合变异,该位点为疑似致病性变异。结论CDG-Ik型为常染色体隐性遗传病,对于不明原因的多脏器损害,特别是合并智能运动发育落后、斜视、小脑萎缩的患儿应考虑本病的可能,ALG1基因检测有助诊断。

关键词：先天性糖基化障碍 ALG1基因突变遗传代谢病

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tRIM30α^(-/-)小鼠模型的构建及其表型分析

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中国预防兽医学报 2021年第2期43卷 191-197页

作者：李昂王辉邵玉乐许曼张子博田璐史鑫琪孟庆文陈洪岩东北农业大学生命科学学院黑龙江哈尔滨150030 中国农业科学院哈尔滨兽医研究所兽医生物技术国家重点实验室/黑龙江省实验动物与比较医学重点实验室黑龙江哈尔滨150069

tRIM30α作为tRIM蛋白家族成员,在天然免疫系统中发挥重要作用。为了研究tRIM30α基因的特性及功能,本研究在小鼠tRIM30α基因第一段编码区选择一段作为靶序列,合成了2条sgRNA,构建了重组质粒pUC19-tRIM30α-sgRNA1/2并体外转录后分别... 详细信息

tRIM30α作为tRIM蛋白家族成员,在天然免疫系统中发挥重要作用。为了研究tRIM30α基因的特性及功能,本研究在小鼠tRIM30α基因第一段编码区选择一段作为靶序列,合成了2条sgRNA,构建了重组质粒pUC19-tRIM30α-sgRNA1/2并体外转录后分别与体外转录并加poly(A)尾的pt7-SpCas9-SV40混合后经显微注射至C57BL/6近交系小鼠的受精卵中,获得第一代(F0代)tRIM30α基因敲除的小鼠并经PCR鉴定。将其与野生型(Wt)小鼠合笼繁育出tRIM30α^(+/-)小鼠(F1代),经PCR鉴定后再通过全同胞交配的方式获得tRIM30α基因敲除的纯合子(tRIM30α^(-/-))小鼠(F2代)。通过PCR和测序在DNA水平鉴定tRIM30α^(-/-)小鼠各组织(心、肝、脾、肺、肾、脑、肌肉)tRIM30α基因的敲除情况;经Rt-PCR检测tRIM30α^(-/-)小鼠上述各组织tRIM30α基因mRNA的转录水平;利用PCR分别扩增小鼠中的3个高频脱靶位点(trim30d、D6WSu163e、Sbk1)后经t7E1酶切检测tRIM30α^(-/-)小鼠的脱靶效应。结果显示,分别获得了缺失了4 bp和7 bp片段的两种tRIM30α基因缺失的F0代小鼠(tRIM30α^(+/-)),选择缺失7 bp的tRIM30α^(+/-)小鼠繁育获得F1、F2代小鼠。PCR鉴定结果显示,共获得了7只tRIM30α^(-/-)纯合子小鼠;从DNA水平和mRNA转录水平鉴定结果显示,tRIM30α^(-/-)小鼠各组织的基因组DNA扩增条带均小于Wt小鼠的扩增条带;且其体内未检测到tRIM30α基因的mRNA;tRIM30α^(-/-)小鼠体内也未检测到其他位点的脱靶编辑;tRIM30α^(-/-)小鼠的生长发育、血常规、血生化指标与Wt小鼠相比均无显著差异。以上结果表明tRIM30α^(-/-)小鼠模型构建成功。本研究为探究DNA病毒介导的天然免疫应答中tRIM30α所发挥的作用提供了实验材料和研究依据。

关键词： tRIM30α CRISPR/Cas9 表型分析动物模型

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