Mitochondria Dynamically Transplant into Cells in Vitro and in Mice and Rescue Aerobic Respiration of Mitochondrial DNA-Depleted Motor Neuron NSC-34

It has been reported that transplantation of pheochromocytoma P12 and hepatoma cells’ mitochondria improve the locomotive activity and prevent disease progress in experimental Parkinson’s disease rats. To prepare for mitochondrial transplantation study in human neurodegenerative diseases, we select human fibroblasts as mitochondrial donor because that fibroblasts share many characteristics with mesenchymal stromal cells (MSCs). We isolate human primary fibroblasts and develop a mitochondrial DNA (mtDNA)-depleted mouse motor neuron NSC-34 cells (NSC-34 ρ° cells). Fibroblast and NSC-34 cell’s mitochondria are co-cultured with NSC-34 ρ° cells. Mitochondrial transplantation is observed by fluorescent microscopy. Gene expression is determined by polymerase chain reaction (PCR) and real time PCR (qPCR). Also, mitochondria are injected to mice bearing mammary adenocarcinoma 4T1 cells. We find results as following: 1) There are abundant mitochondria in fibroblasts (337 ± 80 mitochondria per fibroblast). 42.4% of viable mitochondria are obtained by using differential centrifugation. The isolated mitochondria actively transplant into NSC-34 ρ° cells after co-culture. 2) Fibroblasts transfer mitochondria to human mammary adenocarcinoma MCF-7 cells. 3) There is no expression of HLA-I antigen in fibroblast’s mitochondria indicating they can be used for allogeneic mitochondrial transplantation without HLA antigen match. 4) PCR and qPCR show that NSC-34 ρ° cells lose mitochondrially encoded cytochrome c oxidase I (MT-CO1) and mitochondrially encoded NADH dehydrogenase 1 (MT-ND1) and upregulate expression of glycolysis-associated genes hexokinase (HK2), glucose transporter 1 (SLC2A1) and lactate dehydrogenase A (LDHA). 5) Transplantation of NSC-34 mitochondria restores MT-CO1 and MT-ND1 and downregulates gene expression of HK2, SLC2A1 and LDHA. 6) Normal mammary epithelial mitochondria successfully enter to 4T1 cells in mice. Subcutaneous injection of mitochondria is safe for mice. In summary, mitochondrial transplantation replenishes mtDNA and rescues aerobic respiration of diseased cells with mitochondrial dysfunction. Human primary fibroblasts are potential mitochondrial donor for mitochondrial transplantation study in human neurodegenerative diseases.

Nuclear and mitochondrial DNA microsatellite instability in hepatocellular carcinoma in Chinese

AIM：To study the nuclear microsatellite instability (nMSI) at BAT26 and mitochondral microsalellite instability (mtMSI) in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI and mtMSI.METHODS: nMSI was observed with PCR and mtMSI with PCR-SSCP in 52 cases of hepatocellular carcinoma.RESULTS:mtMSI was detected in 11 out of the 52 cases of hepatocellular carcinoma (21.2%). Among the 11 cases of hepatocellular carcinoma with mtMSI, 7 occured in one locus and 4 in 2 loci. The frequency of mtMSI in the 52 cases of hepatocellular carcinoma showed no correlation to sex, age,infection of hepatitis B, liver cirrhosis as well as positive AFP of the patients (P>0.05). In addition, nMSI was detected in 3 out of 52 cases of hepatocellular carcinoma (5.8%) and there was no correlation of the incidence of mtMSI to that of nMSI (P>0.05).CONCLUSION:mtMSI may be involved in the coccurrence and development of hepatocellular carcinoma and it is independent of nMSI.

Change and Signif icance of Mitochondrial DNA Copy Number in Esophageal Squamous Cell Carcinoma

OBJECTIVE To compare the differences of mitochondrial DNA (mtDNA) copies among the tissues of esophageal squamous cell carcinoma (ESCC), para-neoplastic tissue and normal mucous membrane of the esophagus, and to study the relationship between the mtDNA and the occurrence and devel- opment of esophageal squamous cell carcinoma. METHODS The mtDNA copies of 42 specimens with the ESCC, paraneoplastic mucous tissue and normal mucous membrane of the esophagus were determined using real-time fluorescence quantitative PCR. The mtDNA was analyzed using agarose gel electrophoresis. RESULTS The mtDNA from all of the tissues (42/42) from the ESCC, para-neoplastic tissue and normal esophageal mucous membranes was analyzed, showing that there were an average mtDNA copy number of 27.1894×106 μg DNA, 9.4102×106 μg DNA and 5.9347×106 μg DNA, from the respective tissues. There were signifi cant differences (F=27.83, P<0.05) in mtDNA copy number among the three. A positive band was shown at 403 bp after gel electrophoresis of the PCR products, and the lane where the ESCC mtDNA located was rather bright, which was in accordance with the result of the real-time PCR determination. CONCLUSION An increase in the mtDNA copy number is related to the occurrence and development of ESCC.

Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

Phosphatidylglycerol-containing ER-transport vesicles built and restore outer mitochondrial membrane and deliver nuclear DNA translation products to generate cardiolipin in the inner mitochondrial membrane

Phosphatidylglycerol (PG) an important membrane phospholipid required for the synthesis of diphos-phatidylglycerol (DPG) commonly known as cardiolipin (CL) was identified in the fraction of endo-plasmic reticulum (ER)-derived transport vesicles which had no affinity for Golgi. The vesicles were produced in the presence of Brefeldin A (BFA), the agent known to inhibit ER-Golgi transport, and found to display affinity to mitochondria. The analysis revealed that their cargo was not containing proteins that are transported to Golgi, and that their membrane was free of phosphatidylinositol (PI) and ceramides (Cer). The incubation of PG-containing transport vesicles with mitochondria afforded incorporation of their membrane into the Outer Mito-chondrial Membrane (OMM) and formation of lyso-phosphatidylglycerol (LPG). In turn, upon further incubation with fresh transport active cytosol, the mitochondrial LPG was converted to PG. The results of analysis of the OMM, Inner Mitochondrial Mem-brane (IMM) and Inner Mitochondrial Space Components (IMSC) strongly suggest that PG-containing transport vesicles deliver nuclear DNA translation products to the IMSC and thus facilitate CL synthesis in the IMM. In summary, our studies provide evidence that ER-generated PG-enriched transport vesicles represent the general pathway for restitution of mitochondrial membranes and the delivery of nuclear DNA translation products that generate CL, and thus sustain the mitochondrial matrix CL-dependent metabolic reactions.

MSC-mediated mitochondrial transfer restores mitochondrial DNA and function in neural progenitor cells of Leber’s hereditary optic neuropathy

Leber’s hereditary optic neuropathy(LHON)is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA(mtDNA).Unfortunately,the available treatment options for LHON patients are limited due to challenges in mitochondrial replacement.In our study,we reprogramming LHON urine cells into induced pluripotent stem cells(iPSCs)and differentiating them into neural progenitor cells(NPCs)and neurons for disease modeling.Our research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function,confirming the disease phenotype.However,through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells(MSCs),we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON neurons.These findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs,even after their differentiation into neurons.This discovery holds promise as a potential therapeutic strategy for LHON patients.

The Mechanism pf Weichang'an in Inducing Apoptosis of Gastric Cancer SGC7901 Cells

Objective:To investigate the effect of Chinese medicine Compound Weichang'an(胃肠安)for invig-orating the spleen on apoptosis of gastric cancer SGC7901 cells and its possible mechanism.Methods:The gas-trie cancer SGC-7901 cells were divided into different mass concentration groups(0 mg·L^(-1),500 mg·L^(-1)1000 mg·L^(-1),1500 mg·L^(-1),2000 mg·L^(-1)).CCK8 and monoclonal test were applied to detect prolifera-tion ability;comet assay was used to detect DNA damage.After DCFH-DA fluorescent labeling,the level of ROS activity was detected by flow cytometer;after AnnexinV-FTC/PI double labeling,the proportion of apoptotic ellls was detected by flow cytometer;after JC-1 staining,the mi tochondri almembrane potential was detected by flow cytometer;after FTTC-DEVD-FMK staining,the ratio of Caspase activity was detected by flow cytometer.Results:Weichang an inhibited cell proliferation and reduced cell colony formation in a time-dose-dependent manner;the results of comet electrophoresis showed that Weichang'an could induce DNA damage in gastric cancer cells;com-pared with control group.the ratio of Weichang'an's intervention with the apoptosis of gastric cancer cells in-creased(P<0.05),the mitochondrial membrane potential decreased(P<0.05),the activity of Caspase3 and Caspase9 increased(P<0.05),and the intracellular ROS level increased(P<0.05).Among them,the effect of Weichang'an treatment group(1000 mg·L^(-1))was the most significant.Conclusion:Weichang'an has an inhibi-tory effect on the proliferation of gastric cancer SGC7901 cells and can induce cell apoptosis.Its mechanism may be related with the ROS-mediated pathway of mitochondrial apoptosis and DNA damage.

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer＇s disease

Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

Characterization of long-term ex vivo expansion of tree shrew spermatogonial stem cells

Tree shrews(Tupaia belangeri chinensis)share a close relationship to primates and have been widely used in biomedical research.We previously established a spermatogonial stem cell(SSC)-based gene editing platform to generate transgenic tree shrews.However,the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear.Here,we examined the in vivo spermatogenesis potential of tree shrew SSCs cultured across different passages.We found that SSCs lost spermatogenesis ability after long-term expansion(>50 passages),as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia(SPG)-derivedspermatocytesor spermatids marking spermatogenesis.RNA sequencing(RNA-seq)analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers.Specifically,DNA damage response and repair genes(e.g.,MRE11,SMC3,BLM,and GEN1)were down-regulated,whereas genes associated with mitochondrial function(e.g.,NDUFA9,NDUFA8,NDUFA13,and NDUFB8)were up-regulated after expansion.The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells.Supplementation with nicotinamide adenine dinucleotide(NAD+)precursor nicotinamide riboside(NR)exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture.Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended in vitro maintenance.

由mtDNA清除THP-1细胞构建的人单核/巨噬细胞系Rho0细胞周期、凋亡、吞噬功能、炎症因子表达变化

目的 观察由线粒体DNA(mtDNA)清除人单核细胞白血病细胞(THP-1细胞)构建的人单核/巨噬细胞系Rho0细胞周期、凋亡、吞噬功能、炎症因子表达变化。方法 取THP-1细胞,使用溴化乙锭(EB)清除细胞中mtDNA,构建新的人单核/巨噬细胞Rho0。取Rho0细胞,分别给予1 mg/mL LPS或溶媒刺激24 h(计为Rho0-LPS组、Rho0-溶媒组);另取未经EB处理的THP-1细胞,分别给予1 mg/mL LPS或溶媒刺激24 h(计为Control-LPS组、Control-溶媒组);采用流式细胞术PI染色检测各组细胞周期,流式细胞术Annexin V-FITC/PI法测算各组凋亡细胞数,Red-Zymosan染料吞噬实验评估各组细胞吞噬功能(平均荧光强度)。取Rho0细胞(Rho0组)和取未经EB处理的THP-1细胞(Control组),采用RT-qPCR法检测炎症因子(IL-1α、IL-1β、TNF-α、IL-6、IL-8、IL-10、IL-12 mRNA)。结果 与Control-溶媒组比较,Rho0-溶媒组G0~G1期、S期、G2/M期比例降低及细胞凋亡数增加和平均荧光强度增强,Control-LPS组细胞凋亡数增加和平均荧光强度增强(P均<0.05);与Rho0-溶媒组比较,Rho0-LPS组G0~G1期比例降低及细胞凋亡数增加(P均<0.05)。与Control组比较,Rho0组IL-1β、TNF-α、IL-8、IL-10 mRNA表达升高(P均<0.05)。结论 清除mtDNA可导致Rho0细胞周期停滞,促进细胞凋亡,增强细胞吞噬功能及促炎功能。

Mutations of mitochondrion DNA in mouse tumors

Objective： To ascertain the variations of mitochondrion DNA （mtDNA） in mouse tumors and to inquire into the relationship between mutations of mtDNA and carcinogenesis Methods： The variations of D-loop, ND3 and tRNA^Met＋Glu＋Ile gene fragments of mtDNA from six tumor cell lines of mice were analyzed by PCR technology with restriction fragment length polymorphism analysis （polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP） and single strand conformation polymorphism analysis （SSCP-PCR） method. Results： ND3 and tRNA^Met＋Glu＋Ile gene fragments ofmtDNA from the tumors showed no variation in 27 endonuclease sites; D-loop ofmtDNA from Hca-F had an additional endonuclease sites of Hinf I in contrast to that of the inbred mouse. Deeply analyzed by PCR-SSCP, the D-loop ofmtDNA was found to possess mutations in 4 of 6 tumors. Conclusion： D-loop is the hot spot of tumor mtDNA mutation which can act as contributors to the carcinogenic

Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine

Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials.However,the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored.Here,we demonstrate that oxidized mitochondrial DNA(mtDNA)and stimulator of interferon genes(STING)signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine.Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells.Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells(DCs).Oxidized mtDNA,as a DAMP or adjuvant,activated the STING-TBK1-IRF3-IFN-β pathway in DCs,which subsequently cross-presented irradiated tumor cell-derived antigens to CD8^(+)T cells and elicited antitumor immunity.The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity,which may have implications for new strategies to improve the efficacy of irradiated vaccines.

槲皮素抑制异烟肼诱导的L-02细胞线粒体氧化应激性DNA损伤

目的:探讨活性氧(ROS)介导的线粒体氧化损伤在异烟肼(INH)诱导L-02细胞DNA损伤中的作用及槲皮素对细胞的保护作用。方法:建立体外培养INH致肝细胞L-02损伤的模型,将细胞分为对照(control)组、INH组、槲皮素低剂量(Que low)及高剂量(Que high)组。利用彗星试验评价细胞DNA损伤;制备L-02细胞线粒体,应用荧光探针DCFH-DA和rhodamine 123检测细胞线粒体ROS水平及线粒体膜电位(ΔΨm);采用TBA法测定丙二醛(MDA)含量;应用黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)的活性;采用Western blotting法检测细胞中Bcl-2和Bax蛋白表达,计算Bax/Bcl-2值。结果:INH可诱导L-02细胞DNA损伤,使细胞线粒体ROS水平、细胞MDA含量及Bax/Bcl-2值明显增高,并使细胞ΔΨm值和SOD活性明显下降。而槲皮素能减轻细胞DNA损伤,减少细胞ROS水平,增加细胞ΔΨm值,降低细胞MDA含量,增加SOD活性,减少Bax/Bcl-2值。结论:INH可通过诱导细胞线粒体氧化应激导致L-02细胞DNA损伤。槲皮素能减轻INH诱导L-02细胞的DNA损伤,对L-02细胞具有保护作用,可能与其抑制ROS介导的线粒体氧化损伤有关。

人食管鳞癌EC9706细胞线粒体DNA与凋亡的关系

目的建立人食管鳞癌EC9706细胞的无线粒体DNA(ρ°)细胞,探讨食管癌线粒体DNA与凋亡的关系。方法在细胞培养液中加EB50μg/ml、尿嘧啶50μg/ml、丙酮酸100μg/ml,进行连续传代培养,获得完全缺失mtDNA的细胞(ρ°细胞);运用实时荧光定量PCR技术,检测EB处理后不同时间的人食管鳞癌细胞EC9706 mtDNA的拷贝数,并采用琼脂糖凝胶电泳对mtDNA进行定性检测;采用TUNEL染色和流式细胞技术,检测EB处理后不同时间人食管鳞癌细胞EC9706的凋亡情况。结果成功建立了人食管鳞癌细胞EC9706的ρ°细胞,经实时荧光定量PCR鉴定,发现在EB存在下,随着细胞分裂,mtDNA拷贝数进行性减少,直到12天,mtDNA完全丢失;流式细胞术检测结果显示,EC9706细胞EB处理后,第4天、8天及12天细胞凋亡率(%)分别为(2.78±1.04)、(11.68±1.85)、(26.62±1.06),与对照组相比,差异均有统计学意义(P<0.05);TUNEL检测结果与上述一致,从第4天到第12天凋亡也逐渐增加。结论成功建立了EC9706ρ°细胞。随着EC9706细胞mtDNA拷贝数量的逐渐减少,细胞凋亡率逐渐增加,表明mtDNA在诱导细胞凋亡中起着一定调控作用,提示选择性地诱导食管癌细胞mtDNA损伤,使食管癌细胞mtDNA拷贝数量明显减少,进而诱导细胞凋亡,可望成为食管癌生物治疗的一个新靶点。

人食管鳞癌EC9706细胞线粒体DNA中ND1基因突变的检测及意义

目的通过对人食管鳞癌EC9706细胞线粒体DNA(mtDNA)中ND1基因进行检测,分析其基因突变的意义。方法培养人食管鳞癌EC9706细胞,提取其mtDNA中的ND1基因,并测序。结果测序发现,人食管鳞癌EC9706细胞mtDNA中ND1基因的3 971处出现点突变,由C突变为T。结论人食管鳞癌EC9706细胞中mtDNA的ND1基因的突变与食管癌发生、发展关系密切。

Cell models and drug discovery for mitochondrial diseases

Mitochondrion is a semi-autonomous organelle,important for cell energy metabolism,apoptosis,the production of reactive oxygen species(ROS),and Ca2+homeostasis.Mitochondrial DNA(mtDNA)mutation is one of the primary factors in mitochondrial disorders.Though much progress has been made,there remain many difficulties in constructing cell models for mitochondrial diseases.This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases.Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells,fibroblastoid cells,cytoplasmic hybrid(cybrid)cell lines,and induced pluripotent stem cells(iPSCs)-derived differentiation cells in the study of mitochondrial disorders,as well as offering discussion of roles and advances of these cell models,particularly in the screening of drugs.

^(60)Co照射后SMMC-7721细胞线粒体DNA部分D-loop区辐照损伤的初步研究

目的线粒体DNA(mitochondrial DNA,mtDNA)的变化可能损害氧的利用,导致细胞的氧化和减少能量的产生,从而引起肿瘤细胞的凋亡。文中观察SMMC-7721细胞在接受不同剂量60Coγ射线照射后,线粒体DNA部分D-loop区碱基的损伤规律及特定的断裂敏感点。方法根据人线粒体DNA非编码区的基因序列设计相应的引物序列,再通过接头介导PCR(LM-PCR)及基因扫描来检测其断裂程度、位点及规律。结果在接受不同剂量γ射线照射后,通过ligation-media-ted PCR(LM-PCR)和基因扫描检测,发现各剂量都有相同大小的片段,即存在相同的断裂位点,且这些位点并非随机分布,位点的损伤频率也随着剂量的增加而呈现递增趋势。同时,随着剂量的增加还出现了新的断裂位点,且在一定范围内出现了双链断裂。结论线粒体DNAD-loop区在60Co照射后,产生的一系列断裂敏感位点和双链断裂及本身特有的突变位点,可能对SMMC-7721细胞辐射后的细胞凋亡起到重要作用,推测mtDNA很有可能是电离辐射易感的靶点,mtDNA的变化能够作为肿瘤细胞辐照前后损伤的一个重要指标。

血浆无细胞线粒体外线粒体DNA与牙周炎临床指标的相关性研究

目的血浆无细胞线粒体外线粒体DNA(cf-exmtDNA)具有促炎潜能,本文探讨血浆cf-exmtDNA与牙周炎临床指标的相关性。方法纳入18~45岁受试者78人,其中牙周健康者11人,牙龈炎患者11人,牙周炎患者56人。检查并记录基线牙周指标、年龄、性别、体质指数(BMI)和空腹血糖(FBG)。取4 mL抗凝静脉血,采用二次离心法提取其中cf-exmtDNA,使用实时荧光定量聚合酶链式反应检测cf-exmtDNA拷贝数。比较不同牙周炎症状态组血浆cf-exmtDNA水平,并对血浆cf-exmtDNA与平均探诊深度(mPD)、平均附着水平(mCAL)、平均出血指数(mBI)、平均菌斑指数(mPLI)、年龄、FBG、BMI等指标进行相关性分析以及多重线性回归分析。结果牙周炎组血浆cf-exmtDNA水平显著高于牙周健康组(P=0.042);样本整体血浆cf-exmtDNA水平与年龄(P=0.023)、mPD(P<0.001)、mCAL(P=0.006)、mBI(P=0.026)呈正相关关系;多重回归分析中,血浆cf-exmtDNA水平主要取决于mPD。结论在18~45岁人群中,牙周炎患者血浆cf-exmtDNA水平较牙周健康者显著升高,血浆cf-exmtDNA水平与年龄、mPD、mCAL、mBI呈正相关关系。

线粒体DNA的研究进展及其法医学应用

线粒体DNA(mitochondrialDNA,mtDNA)是存在于细胞质内的环状DNA。它的存在早在三十多年前就有人提出。如今,关于线粒体的研究领域是生物医学中发展最快的学科之一。它的发展基于一些很基本且有趣的问题的提出,这些问题主要是关于线粒体是如何进化,如何产生能量。另外,在疾病中线粒体基因如何发生突变、细胞凋亡如何受到它的调节、以及衰老如何对线粒体DNA发生影响等问题都有待解答,而且对这些问题的探讨将会对诸如人类学、法医学以及疾病的治疗有很大的用途。

人类线粒体DNA突变与癌症

细胞中的线粒体在细胞的能量代谢等功能中发挥了重要的作用。人类的肿瘤形成与线粒体DNA(mtDNA)存在着复杂的关联,在多种癌细胞中均检测到mtDNA的突变。文章综述了癌细胞中的mtDNA突变与癌症发生的相关性,并讨论了部分突变产生的原因及在癌症中进行mtDNA突变检测的应用前景。