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Mitochondrial replacement techniques or therapies (MRTs) to improve embryo development and to prevent mitochondrial disease transmission

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Journal of Genetics and Genomics 2017年第8期44卷 371-374页

作者： Xiang-Hong Ou qing-yuan sun Reproductive Medicine Center The 2nd People's Hospital of Guangdong ProvinceGuangzhou 510317China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China

The mitochondrion which contains its own double-stranded circular DNA is a semi-independent organelle that plays critical roles in cell activity. Mitochondrial DNA （mtDNA） is maternally inherited through several mechanisms that have been proposed （Luo et al., 2013） and, if mitochondrial mutations are inherited to the offspring, it is possible to cause mitochondrial diseases such as neuropathy, cardiomyopathy, myopathy, and liver failure.

关键词： mtDNA Mitochondrial replacement techniques or therapies to improve embryo development and to prevent mitochondrial disease transmission

Aberrant DNA methylation in 5′ regions of DNA methyltransferase genes in aborted bovine clones

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Journal of Genetics and Genomics 2008年第9期35卷 559-568页

作者： Jinghe Liu Xingwei Liang Jiaqiao Zhu Liang Wei Yi Hou Da-yuan Chen qing-yuan sun State Key Laboratory of Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Graduate School of Chinese Academy of Sciences Beijing 100101 China

High rate of abortion and developmental abnormalities is thought to be closely associated with inefficient epigenetic reprogramming of the transplanted nuclei during bovine cloning. It is known that one of the important mechanisms for epigenetic reprogramming is DNA methylation. DNA methylation is established and maintained by DNA methyltransferases （DNMTs）, therefore, it is postulated that the inefficient epigenetic reprogramming of transplanted nuclei may be due to abnormal expression of DNMTs. Since DNA methylation can strongly inhibit gene expression, aberrant DNA methylation of DNMT genes may disturb gene expression. But presently, it is not clear whether the methylation abnormality of DNMT genes is related to developmental failure of somatic cell nuclear transfer embryos. In our study, we analyzed methylation patterns of the 5＇ regions of four DNMT genes including Dnmt3a, Dnmt3b, Dnmtl and Dnmt2 in four aborted bovine clones. Using bisulfite sequencing method, we found that 3 out of 4 aborted bovine clones （AF1, AF2 and AF3） showed either hypermethylation or hypomethylation in the 5＇ regions of Dnmt3a and Dnmt3b, indicating that Dnmt3a and Dnmt3b genes are not properly reprogrammed. However, the individual AF4 exhibited similar methylation level and pattern to age-matched in vitro fertilized （IVF） fetuses. Besides, we found that the 5＇ regions of Dnmtl and Dnmt2 were nearly completely unmethylated in all normal adults, IVF fetuses, sperm and aborted clones. Together, our results suggest that the aberrant methylation of Dnmt3a and Dnmt3b 5＇ regions is probably associated with the high abortion of bovine clones.

关键词： DNA methylation DNA methyltransferase epigenetic reprogramming somatic cell nuclear transfer cow

New Understandings on Folliculogenesis/Oogenesis Regulation in Mouse as Revealed by Conditional Knockout

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Journal of Genetics and Genomics 2012年第2期39卷 61-68页

作者： Meng-Wen Hu Zhen-Bo Wang Heide Schatten qing-yuan sun a State Key Laboratory of Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Graduate School of Chinese Academy of Sciences Beijing 100101China Department of Veterinary Pathobiology University of MissouriColumbiaMO 65211USA

In comparison to conventional knockout technology and in vitro research methods, conditional gene knockout has remarkable advantages. In the past decade, especially during the past five years, conditional knockout approaches have been used to study the regulation of folliculogenesis, follicle growth, oocyte maturation and other major reproductive events. In this review, we summarize the recent findings about folliculogenesis/oogenesis regulation, including the functions of four signaling cascades or glycoprotein domains that have been extensively studied by conditional gene deletion. Several other still fragmented areas of related work are introduced which are awaiting clarification. We have also discussed the future potential of this technology in clarifying gene functions in reproductive biology.

关键词： Conditional knockout Folliculogenesis Oogenesis Mouse

Molecules and mechanisms controlling the active DNA demethylation of the mammalian zygotic genome

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Protein & Cell 2014年第11期5卷 827-836页

作者： Jun-Yu Ma Teng Zhang Wei Shen Heide Schatten qing yuan sun College of Animal Science and Technology Qingdao Agricultural University Qingdao 266109 China State Key Laboratory of Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Department of Veterinary Pathobiology University of Missouri Columbia MO 65211 USA

The active DNA demethylation in early embryos is essential for subsequent development. Although the zygotic genome is globally demethylated, the DNA methylation of imprinted regions, part of repeat sequences and some gamete-specific regions are maintained. Recent evidence has shown that multiple proteins and biological pathways participate in the regulation of active DNA demethylation, such as TET proteins, DNA repair pathways and DNA methyltransferases. Here we review the recent understanding regarding proteins associated with active DNA demethylation and the regulatory networks controlling the active DNA demethylation in early embryos.

关键词： active DNA demethylation zygote 5-hmC5-mC preimplantation embryo TET proteins

Why is oocyte aneuploidy increased with maternal aging?

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Journal of Genetics and Genomics 2020年第11期47卷 659-671页

作者： Jun-Yu Ma Sen Li Lei-Ning Chen Heide Schatten Xiang-Hong Ou qing-yuan sun Fertility Preservation Lab Reproductive Medicine CenterGuangdong Second Provincial General HospitalGuangzhou510317China Department of Veterinary Pathobiology University of MissouriColumbiaMO 65211USA State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China

One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy,which is increased with maternal aging.Numerous possible causes of oocyte aneuploidy in aged women have been proposed,including cross-over formation defect,cohesin loss,spindle deformation,spindle assembly checkpoint malfunction,microtubule-kinetochore attachment failure,kinetochore mis-orientation,mitochondria dysfunction-induced increases in reactive oxygen species,protein over-acetylation,and DNA damage.However,it still needs to be answered if these aneuploidization factors have inherent relations,and how to prevent chromosome aneuploidy in aged oocytes.Epidemiologically,oocyte aneuploidy has been found to be weakly associated with higher homocysteine concentrations,obesity,ionizing radiation and even seasonality.In this review,we summarize the research progress and present an integrated view of oocyte aneuploidization.

关键词： Aging Oocyte Aneuploidy Cohesin SAC Spindle Mitochondria Meiosis DNA damage

A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2263-2280页

作者： Leilei Wang Shanshan He Rong Liu yuan Xue yuan Quan Rongying Shi Xueying Yang qing Lin Xun sun Zhirong Zhang Ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Chemotherapeutics can induce immunogenic cell death(ICD)in tumor cells,offering new possibilities for cancer therapy.However,the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment(TME).Here,we developed a pH/reactive oxygen species(ROS)dual-response system to enhance chemoimmunotherapy for melanoma.The system productively accumulated in tumors by specific binding of phenylboronic acid(PBA)to sialic acids(SA).The nanoparticles(NPs)rapidly swelled and released quercetin(QUE)and doxorubicin(DOX)upon the stimulation of tumor microenvironment(TME).The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice,significantly enhancing the effects of the combination.Our study revealed DOX was an ICD inducer,stimulating immune responses and promoting maturation of dendritic cells(DCs).Additionally,QUE served as a TME regulator by inhibiting the cyclooxygenase-2(COX2)-prostaglandin E2(PGE2)axis,which influenced various immune cells,including increasing cytotoxic T cells(CLTs)infiltration,promoting M1 macrophage polarization,and reducing regulatory T cells(Tregs)infiltration.The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment.This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

关键词： Quercetin Nanoparticle Responsiveness Chemoimmunotherapy Tumor immune microenvironment

Research on the prognostic value of adjusting intraperitoneal threedimensional quality evaluation mode in laparoscopic cholecystectomy patients

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1078-1086页

作者： yuan Zhou Zhan-qing Chen Operating Room Lianyungang Hospital of Traditional Chinese MedicineLianyungang 222000Jiangsu ProvinceChina Operating Room The Second People's Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical UniversityLianyungang 222000Jiangsu ProvinceChina

BACKGROUND Benign gallbladder diseases have become a high-prevalence condition not only in China but also worldwide.The main types of benign gallbladder diseases include gallbladder polyps,acute and chronic cholecystitis,and gallstones,with gallstones being the most common,accounting for over 70%of cases.Although the mortality rate of benign gallbladder diseases is low,they carry obvious potential risks.Studies have shown that an increased incidence of benign gallbladder diseases can increase the risk of cardiovascular diseases and gallbladder cancer,resulting in a substantial disease burden on patients and their families.AIM To assess the medical utility of the Configuration-Procedure-Consequence(CPC)three-dimensional quality evaluation model in modulating the prognosis of laparoscopic cholecystectomy patients.METHODS A total of 98 patients who underwent laparoscopic cholecystectomy in our hospital from February 2020 to January 2022 were selected as the subjects.According to the random number table method,they were divided into a study group and a control group,with 49 patients in each group.The control group received routine perioperative care,while the study group had the addition of the CPC three-dimensional quality evaluation.The postoperative recovery-related indicators(time to first flatus,time to oral intake,time to ambulation,hospital stay),stress indicators(cortisol and adrenaline levels),distinctions in anxiety and RESULTS The time to first flatus,time to oral intake,time to ambulation,and hospital stay of the study group patients were obviously lower than those of the control group patients,with statistical significance(P0.05).However,on the 3rd day after surgery,the cortisol and adrenaline levels,as well as SAS and SDS scores of the study gr

关键词： Configuration-Procedure-Consequence Three-dimensional quality evaluation Laparoscopic Cholecystectomy Recovery process Anxiety and depression Complications

Winter extreme precipitation over the Tibetan Plateau influenced by Arctic sea ice on interdecadal timescale

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Advances in Climate Change Research 2024年第1期15卷 42-51页

作者： qing-Quan LI Miao BI Song YANG qing-yuan WU Yi-Hui DING Xin-Yong SHEN Xiao-Ting sun Meng-Chu ZHAO China Meteorological Administration Key Laboratory for Climate Prediction Studies National Climate CentreBeijing 100081China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science and TechnologyNanjing 210044China CMA Key Open Laboratory of Transforming Climate Resources to Economy Chongqing Institute of Meteorological SciencesChongqing 401147China School of Atmospheric Sciences and Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies Sun Yat-sen University Zhuhai 519082China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519082China

The Tibetan Plateau(TP)and the Arctic are the most sensitive regions to global climate change.However,the interdecadal varibility of winter extreme precipitation over the TP and its linkage with Arctic sea ice are still unclear.In this study,the characteristics and mechisnems of the TP extreme precipitation(TPEP)influenced by Arctic sea ice on interdecadal timescale are studied based on the daily precipitation,monthly sea ice concentration and ERA5 reanalysis data from 1980 to 2018.We found that the dominant mode of the TPEP in winter mostly exhibits a uniform spatial variation on the interdecadal timescale,with an opposite weak variation in the southeastern TP,and the Arctic sea ice concentration(SIC)before 2002 are larger than that after 2003.The interdecadal variation of TPEP is affected by two teleconnection wave trains regulated by the Barents and Kara Sea ice.In the light ice years,a remarkable positive geopotential height(HGT)anomaly appears over the Barents-Kara Sea and a remarkable negative HGT anomaly is located over the Lake Baikal.Two wave trains originating over the Barents-Kara Sea can be observed.The southern branch forms a wave train through the North Atlantic along the subtropical westerly jet stream,showing a‘+-+-+'pattern of HGT anomalies from Arctic to the TP.Negative HGT anomaly controls the western TP,which creates dynamic and water vapor conditions for the TPEP.The northern branch forms a wave train through the Lake Baikal and the southeast of the TP,showing a‘+-+'HGT anomaly distribution.Positive HGT anomaly controls the southeastern TP,which is not conducive to precipitation in the region.When the SIC in the Barents-Kara Sea increases,the situation is opposite.The above analysis also reveals the reason for the difference in the east-west distribution of the TPEP.

关键词： Arctic sea ice Tibetan Plateau Winter extreme precipitation Rossby wave activity Interdecadal variation

Subcellular distribution of prohibitin 1 in rat liver during liver regeneration and its cellular implication

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World Journal of Hepatology 2024年第1期16卷 65-74页

作者： qing-Ju sun Tao Liu Department of Clinical Laboratory Navy No.971 HospitalQingdao 266072Shandong ProvinceChina Department of Infectious Diseases Navy No.971 HospitalQingdao 266071Shandong ProvinceChina

BACKGROUND The function of prohibitin 1(Phb1)during liver regeneration(LR)remains relatively unexplored.Our previous research identified downregulation of Phb1 in rat liver mitochondria 24 h after 70%partial hepatectomy(PHx),as determined by subcellular proteomic analysis.AIM To investigate the potential role of Phb1 during LR.METHODS We examined changes in Phb1 mRNA and protein levels,subcellular distribution,and abundance in rat liver during LR following 70%PHx.We also evaluated mitochondrial changes and apoptosis using electron microscopy and flow cytometry.RNA-interference-mediated knockdown of Phb1(PHBi)was performed in BRL-3A cells.RESULTS Compared with sham-operation control groups,Phb1 mRNA and protein levels in 70%PHx test groups were downregulated at 24 h,then upregulated at 72 and 168 h.Phb1 was mainly located in mitochondria,showed a reduced abundance at 24 h,significantly increased at 72 h,and almost recovered to normal at 168 h.Phb1 was also present in nuclei,with continuous increase in abundance observed 72 and 168 h after 70%PHx.The altered ultrastructure and reduced mass of mitochondria during LR had almost completely recovered to normal at 168 h.PHBi in BRL-3A cells resulted in increased S-phase entry,a higher number of apoptotic cells,and disruption of mitochondrial membrane potential.CONCLUSION Phb1 may contribute to maintaining mitochondrial stability and could play a role in regulating cell proliferation and apoptosis of rat liver cells during LR.

关键词： Prohibitin 1 Liver regeneration Subcellular proteomic analysis Mitochondrial stability Cell proliferation