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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNAdamage

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction     mitochondrial DNA damage     in situ hydrophobic environment trigger     fluorescence probe     apoptosis    

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Bacterial inactivation, DNA damage, and faster ATP degradation induced by ultraviolet disinfection

Chao Yang, Wenjun Sun, Xiuwei Ao

《环境科学与工程前沿（英文）》 2020年 第14卷 第1期 doi: 10.1007/s11783-019-1192-6

摘要： • Long amplicon is more effective to test DNA damage induced by UV. • ATP in bacteria does not degrade instantly but does eventually after UV exposure. • After medium pressure UV exposure, ATP degraded faster. The efficacy of ultraviolet (UV) disinfection has been validated in numerous studies by using culture-based methods. However, the discovery of viable but non-culturable bacteria has necessitated the investigation of UV disinfection based on bacterial viability parameters. We used quantitative polymerase chain reaction (qPCR) to investigate DNA damage and evaluated adenosine triphosphate (ATP) to indicate bacterial viability. The results of qPCR effectively showed the DNA damage induced by UV when using longer gene amplicons, in that sufficiently long amplicons of both 16S and gadA indicated that the UV induced DNA damages. The copy concentrations of the long amplicons of 16S and gadA decreased by 2.38 log/mL and 1.88 log/mL, respectively, after exposure to 40 mJ/cm2 low-pressure UV. After UV exposure, the ATP level in the bacteria did not decrease instantly. Instead it decreased gradually at a rate that was positively related to the UV fluence. For low-pressure UV, this rate of decrease was slow, but for medium pressure UV, this rate of decrease was relatively high when the UV fluence reached 40 mJ/cm2. At the same UV fluence, the ATP level in the bacteria decreased at a faster rate after exposure to medium-pressure UV.

关键词： UV disinfection     DNA damage     qPCR     ATP    

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Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 185-190 doi: 10.15302/J-FASE-2014035

摘要： DNA damage is one of the most common threats to meiotic cells. It has the potential to induce infertility and genetic abnormalities that may be passed to the embryo. Here, we reviewed exogenous factors which could induce DNA damage. Specially, we addressed the different effects of DNA damage on mouse oocytes and embryonic development. Complex DNA damage, double-strand breaks, represents a more difficult repair process and involves various repair pathways. Understanding the mechanisms involved in DNA damage responses may improve therapeutic strategies for ovarian cancer and fertility preservation.

关键词： DNA damage     double-strand breaks (DSBs)     oocyte     embryo    

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Detection of oxidative stress and DNA damage in freshwater snail

Daoud Ali, Huma Ali, Saud Alifiri, Saad Alkahtani, Abdullah A Alkahtane, Shaik Althaf Huasain

《环境科学与工程前沿（英文）》 2018年 第12卷 第5期 doi: 10.1007/s11783-018-1039-6

摘要：

Freshwater snail (Lymnea luteola L.) is good bio indicator of water pollution.

Profenofos is tested for its molluscicidal activity against Lymnea luteola L. snail.

Deleterious effects on some oxidative stress were detected.

Profenofos has a genotoxic effect on Lymnea luteola L. snails.

关键词： Acute toxicity     Profenofos     ROS     oxidative stress     DNA damage     Lymnea luteola    

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NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 177-184 doi: 10.1007/s11684-010-0038-1

摘要： Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD.

关键词： nucleoside reverse transcriptase inhibitors     human immunodeficiency virus     mitochondrial DNA     D loop     mutation    

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The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要：

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词： PARP1     synthetic lethality     PARP inhibitor     DNA repair     cancer     NHEJ    

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Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿（英文）》 2011年 第5卷 第2期   页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要： Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词： ataxia-telangiectasia mutated (ATM)     cell cycle checkpoint     DNA damage     signalling transduction    

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Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells

ZOU Yunfeng, NIU Piye, GONG Zhiyong, YANG Jin, YUAN Jing, WU Tangchun, CHEN Xuemin

《医学前沿（英文）》 2007年 第1卷 第3期   页码 327-332 doi: 10.1007/s11684-007-0063-x

摘要： Selenium compounds, as an effective chemopreventive agent, can induce apoptosis in tumor cells. Reactive oxygen species (ROS) are important mediators in apoptosis induced by various stimuli, which include chemopreventive agents. In this study, we investigated the relationship between ROS and the levels of DNA damage induced by selenite in HepG2 cells. After HepG2 cells were treated with selenite, there was a dose-dependent decrease in cell viability. The levels of ROS induced by selenite were measured by 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) fluorescence, which shows a dose- and time-dependent increase in HepG2 cells. The levels of DNA damage in HepG2 increased in all cells treated with an increasing dose of selenite at 0, 2.5, 5, 10, and 20 μmol/L. N-acetylcysteine (NAC), a known antioxidant, increased cell viability and decreased ROS generation. Moreover, NAC effectively blocked DNA damage induced by selenite. These results revealed that ROS might play an important role in selenite-induced DNA damage that can be reduced by NAC treatment.

关键词： NAC     N-acetylcysteine     DNA     fluorescence     relationship    

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Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要：

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词： diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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Regulation and function of histone acetyltransferase MOF

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 79-83 doi: 10.1007/s11684-014-0314-6

摘要：

The mammalian MOF (male absent on the first), a member of the MYST (MOZ, YBF2, SAS2, and Tip60) family of histone acetyltransferases (HATs), is the major enzyme that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is a prevalent mark associated with chromatin decondensation. MOF has recently been shown to play an essential role in maintaining normal cell functions. In this study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and tumorigenesis. We also analyze the role of MOF as a key regulator of the core transcriptional network of embryonic stem cells.

关键词： MOF     histone acetyltransferase     DNA damage repair     tumorigenesis     embryonic stem cells    

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Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

《医学前沿（英文）》 2022年 第16卷 第2期   页码 216-226 doi: 10.1007/s11684-022-0920-7

摘要： Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

关键词： tsRNA     biomarker     hepatocarcinoma    

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Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 358-365 doi: 10.15302/J-FASE-2017158

摘要： Substantial variation in gene organization and arrangement has been reported for sequenced mitochondrial (mt) genomes from the suborders of the insect order Psocoptera. In this study we sequenced the complete mt genome of , the first representative of the family Stenopsocidae from the suborder Psocomorpha. Relative to the ancestral pattern, rearrangements of a protein-coding gene ( ) and five tRNA genes ( , , , , ) were found. This pattern was similar to that of two barklice from the family Psocidae, with the exception of the translocation of , and Based on comparisons of pairwise breakpoint distances of gene rearrangements, gene number and chromosome number, it was concluded that mt genomes of Stenopsocidae and Psocidae share a relatively conserved pattern of gene rearrangements; mt genomes within the Psocomorpha have been generally stable over long evolutionary history; and mt gene rearrangement has been substantially faster in the booklice (suborder Troctomorpha) than in the barklice (suborders Trogiomorpha and Psocomorpha). It is speculated that the change of life history and persistence of unusual reproductive systems with maternal inheritance contributed to the contrasting rates in mt genome evolution between the barklice and booklice.

关键词： gene rearrangement     mitochondrial genome     Psocoptera     Stenopsocidae     TDRL model    

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N-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probes

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 64-71 doi: 10.1007/s11705-021-2048-8

摘要： Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity. They play an important role in the design of new structural entities for medical applications. Similarly, indoles and their derivatives are found widely in nature. Amino acids, alkaloids and auxin are all derivatives of indoles, as are dyes, and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents. In this work, we combine these two groups organically to construct a rapid response site (within 30 s) for H S, and at the same time, a ratiometric fluorescence response is presented throughout the process of H S detection. As such, the lower detection limit can reach 55.7 nmol/L for H S. In addition, cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H S. Finally, this probe application was verified by imaging H S in nude mice.

关键词： heterocyclic compound     hydrogen sulfide     ratiometric     mitochondrial targeted    

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Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

《医学前沿（英文）》 doi: 10.1007/s11684-023-0983-0

摘要： Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis in a murine model of HFpEF

关键词： mitochondrial fission Ca     Berberine alleviates myocardial     murine model HFpEF    

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p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 412-418 doi: 10.1007/s11684-010-0260-x

摘要： mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type or the functional activation of mutant-type might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant and KYSE 150 with wild-type , p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type , KYSE 70 with mutant , and EC9706 with unknown genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the genotype.

关键词： p53     esophageal squamous cell carcinoma     DNA damage    

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标题 作者 时间 类型 操作

hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNAdamage

期刊论文

Bacterial inactivation, DNA damage, and faster ATP degradation induced by ultraviolet disinfection

Chao Yang, Wenjun Sun, Xiuwei Ao

期刊论文

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

期刊论文

Detection of oxidative stress and DNA damage in freshwater snail

Daoud Ali, Huma Ali, Saud Alifiri, Saad Alkahtani, Abdullah A Alkahtane, Shaik Althaf Huasain

期刊论文

NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

期刊论文

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

期刊论文

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

期刊论文

Relationship between reactive oxygen species and sodium-selenite-induced DNA damage in HepG2 cells

ZOU Yunfeng, NIU Piye, GONG Zhiyong, YANG Jin, YUAN Jing, WU Tangchun, CHEN Xuemin

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Regulation and function of histone acetyltransferase MOF

null

期刊论文

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

期刊论文

Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

期刊论文

N-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probes

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

期刊论文

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

期刊论文

p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

期刊论文