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AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy

Chinese Medical Journal 2024年第2期137卷 222-231页

作者： Yichun Yin Jian Wang Junxuan Yi Kaiyue Zhang Zimeng Yin Shunzi Jin Baisong Zheng Public Health of College Jilin UniversityJilinChangchun 130021China Institute of Virology and AIDS Research The First Hospital of Jilin UniversityJilinChangchun 130021China NHC Key Laboratory of radiobiology(Jilin University) JilinChangchun 130021China

Background:Radiation(IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment(TME).Wee1,a cell cycle regulator,can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1(CDK1).Meanwhile,programed death-1/programed death ligand-1(PD-1/PDL-1)blockade is closely related to *** study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody(anti-PD-1 Ab)on radiosensitization of ***:The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide(MTT)assay on human and mouse hepatoma cells HepG2,Hepa1-6,and *** anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro.A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice,which were divided into control group,IR group,AZD1775 group,IR+AZD1775 group,IR+anti-PD-1 Ab group,and the IR+AZD1775+anti-PD-1 Ab *** CD8^(+)T cells in TME were analyzed by flow ***:Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in ***1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA ***1775 treatment also reduced the proportion of PD-1^(+)/CD8^(+)T cells in the spleen of hepatoma subcutaneous xenograft *** studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferonγ(IFNγ)^(+)or Ki67^(+)CD8 T cells and decreasing the levels of CD8^(+)Tregs cells in the tumor and spleen of the hepatoma mice model,indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγexpression,enhancing CD8^(+)T cells proliferation,and weakening CD8^(+)T cells ***:This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiothera

关键词： Hepatoma Radiation AZD1775 Anti-PD-1 antibody DNA damage Tumor microenvironment

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Impact of immunotherapy on liver metastasis

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 1969-1972页

作者： Zhuo Fu Ming-Wei Wang Ya-Hui Liu Yan Jiao Medical College Inner Mongolia Minzu UniversityTongliao 028000Inner Mongolia Autonomous RegionChina Ministry of Health Key Laboratory of radiobiology School of Public Health of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

This editorial discusses the article“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”published in the latest edition of the World Journal of Gastrointestinal *** has achieved outstanding success in tumor ***,the presence of liver metastasis(LM)restrains the efficacy of immunotherapy in various tumors,including lung cancer,colorectal cancer,renal cell carcinoma,melanoma,and gastric cancer.A decrease in CD8+T cells and nature killer cells,along with an increase in macrophages and regulatory T cells,was observed in the microenvironment of LM,leading to immunotherapy *** studies are necessary to determine the best strategy for enhancing the effectiveness of immunotherapy in patients with LM.

关键词： Immunotherapy Liver metastasis Tumor microenvironment Resistance T cells

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Occurrence and prevention of incisional hernia following laparoscopic colorectal surgery

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 1973-1980页

作者： Xi-Wen Wu Ding-Quan Yang Ming-Wei Wang Yan Jiao The First Operating Room The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina department of Gastrointestinal and Colorectal Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Ministry of Health Key Laboratory of radiobiology School of Public Health of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Hepatobiliary and Pancreatic Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

Among minimally invasive surgical procedures,colorectal surgery is associated with a notably higher incidence of incisional hernia(IH),ranging from 1.7% to 24.3%.This complication poses a significant burden on the healthcare system annually,necessitating urgent attention from *** a study published in the World Journal of Gastrointestinal Surgery,Fan et al compared the incidence of IH among 1614 patients who underwent laparoscopic colorectal surgery with different extraction site locations and evaluated the risk factors associated with its *** editorial analyzes the current risk factors for IH after laparoscopic colorectal surgery,emphasizing the impact of obesity,surgical site infection,and the choice of incision location on its ***,we summarize the currently available preventive measures for *** the low surgical repair rate and high recurrence rate associated with IH,prevention deserves greater research and attention compared to treatment.

关键词： Incisional hernia Laparoscopy Colorectal surgery Risk factor Prevention

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Microalgae Improve the Photosynthetic Performance of Rice Seedlings(Oryza sativa L.)under Physiological Conditions and Cadmium Stress

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Phyton-International Journal of Experimental Botany 2022年第7期91卷 1365-1380页

作者： Ekaterina Yotsova Martin Stefanov Georgi Rashkov Margarita Kouzmanova Anelia Dobrikova Emilia Apostolova Institute of Biophysics and Biomedical Engineering Bulgarian Academy of SciencesSofiaBulgaria department of Biophysics and radiobiology Biological FacultySofia UniversitySofiaBulgaria

The aim of this study was to assess the impact of the microalgae Chlorella vulgaris on the rice seedlings at physiological conditions and under cadmium(Cd)*** examined the effects of *** in the nutrient solution on rice seedlings grown hydroponically in the presence and the absence of 150μM CdCl2,using the low(77 K)temperature and pulse amplitude modulated(PAM)chlorophyll fluorescence,P700 photooxidation measurements,photochemical activities of both photosystems,kinetic parameters of oxygen evolution,oxidative stress markers(MDA,H_(2)O_(2) and proline),pigment content,growth parameters and Cd *** revealed that the application *** not only stimulates growth and improves the functions of photosynthetic apparatus under physiological conditions,but also reduces the toxic effect of Cd on rice ***,the presence of the green microalgae in the nutrient solution of the rice seedlings during Cd exposure,signifi-cantly improved the growth,photochemical activities of both photosystems,the kinetic parameters of the oxygen-evolving reactions,pigment content and decreased lipid peroxidation,H_(2)O_(2) and proline *** showed that the alleviation of Cd-induced effects in rice seedlings is a result of the Cd sorption by microalgae,as well as the reduced Cd accumulation in the roots and its translocation from the roots to the shoots.

关键词： Chlorella vulgaris growth parameters low temperature chlorophyll fluorescence PAM chlorophyll fluorescence photosynthesis rice stress markers

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Evaluation of KTJT-1,an early-maturity mutant of sweet sorghum acquired by carbon ions irradiation

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Nuclear Science and Techniques 2014年第2期25卷 47-50页

作者：董喜存李文建 radiobiology department Institute of Modern PhysicsChinese Academy of Sciences

Sweet sorghum has the potential of becoming a useful energy *** early-maturity mutant of sweet sorghum,KFJT-1,was obtained by carbon ions irradiation of KFJT-CK,a wild *** this paper,we evaluate the mutant from the length and fresh weight of radicle and leaves after seed germination,the growth rate at the elongation stage,and the internodal parameters under field trail *** results showed that the seedling growth of KFJT-1 was inhibited by carbon ions irradiation,and the leaf length,the fresh weight of radicle and leaves from KFJT-1 decreased by 15.32%,76.27%,and 27.08%than those of KFJT-CK,***,the growth rate of KFJT-1 on July 12,July 27 and August 1 increased by 16.19%,59.28%and26.87%,respectively,compared with the *** stalk diameter,total biomass yield and sugar content of KFJT-1 was higher than those of KFJT-CK,despite that the plant height of KFJT-1 was significantly less than KFJT-CK(P < 0.05).In addition,KFJT-1 differed from KFJT-CK in the internodal length,weight and sugar *** conclusion,the early-maturity mutant of KFJT-1 will be a promising variety for sweet sorghum industrialization in Gansu province,China.

关键词：早熟突变甜高粱碳离子离子辐照评价收购节间长度能源作物

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Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

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Military Medical Research 2022年第3期9卷 319-330页

作者： Wei Hu Jia-Wu Liang Song Liao Zhi-Dong Zhao Yu-Xing Wang Xiao-Fei Mao Si-Wei Hao Yi-Fan Wang Heng Zhu Bin Guo Medical School of Chinese People’s Liberation Army(PLA) Beijing100853China department of Stomatology the First Medical CentreChinese PLA General HospitalBeijing100853China Beijing Key Laboratory for radiobiology Beijing Institute of Radiation MedicineBeijing100840China

Background:The healing of bone defects can be challenging for clinicians to manage,especially after exposure to ionizing *** this regard,radiation therapy and accidental exposure to gamma(o inhibit bone formation and increase the risk of *** bone-derivγ)-ray radiation have been shown ted stem cells(CBSCs)are reportedly essential for osteogenic lineages,bone maintenance and *** study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect ***:CBSCs were extracted from C57BL/6 mice and were identified by flow *** CBSCs were subjected to 6 Gyγ-ray radiation followed by treatment with various concentrations of *** effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were *** underlying mechanisms involved in genomic stability,apoptosis and oxidative stress-related signaling were further analyzed by Western blotting,flow cytometry and immunofluorescence ***,postradiation femoral defect models were established and treated with Matrigel and *** effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological ***:The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin(P<0.05).Melatonin maintained genomic stability,reduced postradiation CBSC apoptosis and intracellular oxidative stress,and enhanced expression of antioxidant-related enzymes(P<0.05).Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)levels via the extracellular regulated kinase(ERK)/nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling *** was also found to exhibit antioxidant effects via NRF2 *** vivo experiments demonstrated that the newly formed bone in th

关键词： Melatonin Stem cells Ionizing radiation Bone regeneration

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Novel insights regarding the role of noncoding RNAs in diabetes

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World Journal of Diabetes 2023年第7期14卷 958-976页

作者： Mirjana T Macvanin Zoran Gluvic Vladan Bajic Esma R Isenovic department of radiobiology and Molecular Genetics Vinča Institute of Nuclear Sciences-National Institute of the Republic of SerbiaUniversity of BelgradeBelgrade 11000Serbia department of Endocrinology and Diabetes Clinic for Internal MedicineZemun Clinical HospitalSchool of MedicineUniversity of BelgradeBelgrade 11000Serbia

Diabetes mellitus(DM)is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance,inadequate insulin secretion,or excessive glucagon *** 2021,the global prevalence of diabetes is anticipated to be 10.7%(537 million people).Noncoding RNAs(ncRNAs)appear to have an important role in the initiation and progression of DM,according to a growing body of *** two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding *** are singlestranded,short(17–25 nucleotides),ncRNAs that influence gene expression at the post-transcriptional *** DM has reached epidemic proportions worldwide,it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases *** are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression *** this review,we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these *** hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for *** examine and synthesize recent research that used novel,high-throughput technologies to uncover ncRNAs involved in DM,necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.

关键词： Noncoding RNA miRNA Diabetes Circulating miRNA biomarkers Therapeutic target CRISPR/Cas9 system

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Radiation-induced non-targeted effect of immunity provoked by mitochondrial DNA damage triggered cGAS/ AIM2 pathways

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Radiation Medicine and Protection 2022年第2期3卷 47-55页

作者： Wen Zhang Shi Chen Hua Guan Ping-Kun Zhou Hengyang Medical School University of South ChinaHengyangHunan Province 421001China Beijing Key Laboratory for radiobiology Department of Radiation BiologyBeijing Institute of Radiation MedicineBeijing 100850China

Non-targeted effect is an important complement to the classical target theory of radiation biology which takesnuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism orcell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads toconsiderable damage and the death event. Recent findings indicate that not only cell nucleus but also othercellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where thenon-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data whichprofoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion inthe irradiated cells, such the major apparent performances, signaling pathways and biological *** genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAsdouble-strand breaks directly or indirectly via increased mitochondrial ROS. Under stress conditions, mitochondrial DNA (mtDNA) fragments are released into the cytoplasm. The cytosol mtDNAs are sensed by cGAS andAIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory andimmune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development oftargeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend forcancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggeringcGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.

关键词： Non-targeted effect Mitochondrial DNA cGAS Ionizing radiation Immune response Radiotherapy

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Eutrophication Process of Soil nearby a Sanitary Landfill and Its Influence on Brazilian Savanna Vegetation

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Journal of Environmental Protection 2022年第5期13卷 344-359页

作者： Otacílio Antunes Santana José Imaña-Encinas department of Biofísic and radiobiology Rural University of Pernambuco Recife Brazil department of Forestry University of Brasília Brasília Brazil

This work aimed to demonstrate if exists a relation between eutrophic processes of soil (N, P, K, pH, and organic matter) with phytosociology mosaic of native tree species in Brazilian adjacent sanitary landfill areas of the savanna. One of the study area is located in Brasilia, Federal District, and the other one in Goiania, State of Goiás, 210 km far each other. The methodology consisted in techniques, procedures and specific software applied to this kind of data. There were used plots and subplots for each area and for the vegetation and soil survey. Statistical significance showed that there exists a relationship between eutrophic processes of soil with phytosociology mosaic of native savanna tree species.

关键词： Native Tree Species Savanna Network Neural Model Nutrients

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GSN antibody pretreatment aggravates radiation-induced lung injury in mice

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Nuclear Science and Techniques 2014年第2期25卷 26-31页

作者：王洁袁小鹏顾成黄建峰俞家华刘芬菊 department of radiobiology School of Radiation Medicine and ProtectionMedical College of Soochow University School for Radiological and Interdisciplinary Sciences Soochow University

Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation ***(GSN) is a widespread,multifunctional regulator of cellular structure and *** this work,the roles of GSN in radiation-induced lung injury in Balb/c mice were *** GSN levels in plasma reduced progressively in 72 hours after irradiation,and then increased *** contents in the bronchoalveolar lavage(BAL) fluid increased after thoracic irradiation,whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased *** were intravenously injected with 50 ug GSN antibody 0.5 hour before 20 Gy of thoracic *** antibody pretreatment increased lung inflammation,protein concentration in the BAL fluid and leukocytes infiltration in the irradiated *** activities of superoxidase dismutase(SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups,whereas the levels of malondialdehyde(MDA)*** results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis.

关键词： GSN 肺损伤放射性预处理小鼠抗体 mRNA水平超氧化物歧化酶

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