Food Bioscience
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2024
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IF 4.8
Shaofeng Wang,Quanwei Li,Pan Guo,Luna Su,Tingyu Liang,Wenlan Yu,Qingwen Yang,Jianying Guo,Zhaoxin Tang,Jianzhao Liao
Terbuthylazine (TBA) is a widely employed pesticide that has been found to be a significant source of food and environmental pollution. Excessive exposure to TBA raises considerable apprehension regarding its potential impact on biological health, but its underlying toxic mechanisms have not been reported. Our findings indicated that TBA exposure could cause intestinal damage , as evidenced by decrease in the quantity of cupped cells and decrease in the expression of intestinal barrier-related proteins (Claudin-1, Occludin , ZO-1, and JAM-1). Additionally, exposure to TBA resulted in a significant decrease in the expression levels of oxidative stress-related genes and proteins. Furthermore, the expression of 8-hydroxy-2′-deoxyguanosine was significantly upregulated. Additionally, excessive exposure to TBA led to a substantial release of mitochondrial DNA, which further activated the cGAS-STING pathway and caused TBK1 and IRF3 phosphorylation. Meanwhile, mitophagy was activated under TBA exposure, as evidenced by decrease in the protein and gene levels of p62 and increase in the levels of PINK1 , PARKIN and LC3 II. Therefore, our results suggested that TBA exposure induced oxidative stress in the jejunum and caused mtDNA leakage, for activating the cGAS-STING pathway, which in turn promoted mitophagy . These findings revealed the toxicity mechanisms of TBA, which provided new insights into food safety caused by pesticide contamination.
研究领域:
毒理学
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分子生物学
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DOI
高影响因子
Pharmacognosy Magazine
·
2025
·
IF 0.9
Qing Liu,Ying Lan,Zhe Bai
BackgroundHyperoside is a potential liver cell and mitochondrial protector, but there is no evidence to suggest that hyperoside can effectively treat doxorubicin (DOX) related liver toxicity.PurposeThis study aims to determine the role of hyperoside in DOX related liver toxicity and liver cell damage in vivo and in vitro.MethodsA mouse model of liver toxicity was induced by intraperitoneal injection of DOX, and hyperoside was administered orally for treatment. During this period, the weight and food intake of the mice were recorded. The morphology of mouse liver tissue was observed by hematoxylin and eosin staining. Oxidative stress and inflammatory status in mice were observed through serum inflammatory factors and liver oxidative stress markers. Mitochondrial damage is determined by the degree of mitochondrial DNA damage. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of pyroptosis and genes in the liver and liver cells.ResultsHyperoside can effectively treat DOX-induced oxidative stress and inflammatory status, liver function damage, and hepatocyte necrosis in mice. Further research suggests that the beneficial effect of hyperoside is achieved by inhibiting mitochondrial DNA damage in liver cells.ConclusionThis study indicates that hyperoside improves DOX-induced liver toxicity by inhibiting mitochondrial DNA damage.
研究领域:
药理学
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肝脏病学
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分子生物学
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DOI
高影响因子
NUCLEIC ACIDS RESEARCH
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2024
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IF 16.6
Wang Xu,Qin Geng,Yang Jie,Zhao Chuanqi,Ren Jinsong,Qu Xiaogang
G-quadruplexes (G4s), as an important type of non-canonical nucleic acid structure, have received much attention because of their regulations of various biological processes in cells. Identifying G4s-protein interactions is essential for understanding G4s-related biology. However, current strategies for exploring G4 binding proteins (G4BPs) include pull-down assays in cell lysates or photoaffinity labeling, which are lack of sufficient spatial specificity at the subcellular level. Herein, we develop a subcellular selective APEX2-based proximity labeling strategy to investigate the interactome of mitochondrial DNA (mtDNA) G4s in living cells. By this method, we have identified several mtDNA G4BPs. Among them, a previously unrecognized mtDNA G4BP, DHX30 has been selected as an example to explore its important biofunctions. DHX30 localizes both in cytoplasm and mitochondria and can resolve mtDNA G4s. Further studies have demonstrated that DHX30 unfolds mtDNA G4 in living cells, which results in a decrease in glycolysis activity of tumor cells. Besides, RHPS4, a known mtDNA G4 stabilizer, will reverse this inhibition effect. Benefiting from the high spatiotemporal resolution and the ability of genetically encoded systems to perform the labeling with exquisite specificity within living cells, our approach can realize the identification of subcellular localized G4BPs. Our work provides a novel strategy to map protein interactions of specific nucleic acid features in subcellular compartments of living cells.
研究领域:
分子生物学
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遗传学
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癌症研究
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细胞生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Lanlan Chen,Jingjing Lai,Siqi Dong,Wenjun Liu,Ximei Zhang,Huanghao Yang
Evaluating tumor radiosensitivity is beneficial for the prediction of treatment efficacy, customization of treatment plans, and minimization of side effects. Tracking the mitochondrial DNA (mtDNA) repair process helps to assess tumor radiosensitivity as mtDNA repair determines the fate of the cell under radiation-induced mtDNA damage. However, current probes developed to monitor levels of DNA repair enzymes suffered from complex synthesis, uncontrollable preparation, limited tumor selectivity, and poor organelle-targeting ability. Especially, the correlation between mtDNA repair activity and inherent radiosensitivity of tumors has not yet been explored. Here, we present a mitochondria-targeted DNA-based nanoprobe (TPP-Apt-tFNA) for in situ monitoring of the activity of the mtDNA repair enzyme and evaluating tumor radiosensitivity. TPP-Apt-tFNA consists of a DNA tetrahedral framework precisely modified with three functional modules on each of the three vertexes, that is, the tumor cell-targeting aptamer, the mitochondrion-targeting moiety, and the apurinic/apyrimidinic endonuclease 1 (APE1)-responsive molecule beacon. Once selectively internalized by tumor cells, the nanoprobe targeted the mitochondrion and specifically recognized APE1 to activate fluorescence, allowing the observation of mtDNA repair activity. The nanoprobe showed elevated APE1 levels in the mitochondria of tumor cells under oxidative stress. Moreover, the nanoprobe enabled the illumination of different levels of APE1-mediated mtDNA repair activity in different cell cycle phases. Furthermore, using the nanoprobe in vitro and in vivo, we found that tumor cells with high activity of mtDNA repair, which allowed them to recover from radiation-induced mtDNA lesions, had low sensitivity to radiation and an unsatisfactory radiotherapy outcome. Our work provides a new imaging tool for exploring the roles of mtDNA repair activity in diverse biological processes and for guiding tumor radiation treatment.
研究领域:
生物化学
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分子生物学
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医学影像学
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肿瘤学
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DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Qiang Zhang,Jiamin Lin,Jun Li,Yitian Zhou,Zhiqiang Bi,Hao Yang,Wenli Lu,Tianming Lu,Ruoning Qian,Xi Yang,Yuanyuan Guo,Xiaoqing Xin,Lesan Yan,Shanshan Wang,Ruogu Qi
Platinum-based anticancer drugs exert their effects by forming adducts within nuclear DNA (nDNA), inhibiting transcription and inducing apoptosis in cancer cells. However, tumor cells have evolved mechanisms to resist these drugs. Given mitochondria’s role in cancer and their lack of nucleotide excision repair (NER), targeting mitochondrial DNA (mtDNA) offers a strategy. Herein, a platinum-based terminal-sensitive projectile (TSB) which comprises a heterofunctional tetravalent platinum prodrug as the primary warhead, complemented by a guidance system incorporating triphenylphosphine (TPP) and a secondary warhead, FFa (Fenofibric acid) was developed. TSB was then encapsulated within IR780 coupling DSPE-PEG2K for enhanced delivery (NTSB). This design allows the TSB to be precisely targeted into intertumoral mitochondria as its targeting terminal, releasing free oxaliplatin (OXA) and FFa upon reaching its terminal destination. The accumulation of OXA leads to cross-linking with mtDNA, causing mitochondrial dysfunction, while FFa disrupts the electron transport chain (ETC), impairing oxidative phosphorylation (OXPHOS). Furthermore, under near-infrared (NIR) irradiation, the IR780 component generates a phototherapeutic thermal effect and reactive oxygen species (ROS), which deplete intracellular glutathione (GSH) levels and facilitate Pt cross-linking with mtDNA. Both in vitro and in vivo studies have demonstrated that this comprehensive approach significantly enhances the sensitivity of tumor cells to platinum-based chemotherapeutic drugs.
研究领域:
药理学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2025
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IF 2.5
Jiaxu Wang,Zhengrong Lu,Zhanmin Liu,Qiming Chen
Copy number of cell-free mitochondrial DNA (cf-mtDNA) has garnered significant attention as a biomarker for studying and diagnosing various diseases. However, Quantitative Real-time PCR (qPCR) and Droplet Digital PCR (ddPCR) assays for cf-mtDNA copy number detection require expensive equipment and high experiment conditions. In this study, a colorimetric and fluorescent dual-modality assay was developed for quantitative detection of cf-mtDNA copy number. With G-quadruplex (G4) sequence modified primers, the assay could quantitatively detect cf-mtDNA with spectrophotometry, RGB (Red, Green, Blue) visual method and fluorescence method, which made the application scenarios more diverse. The specificity of dual-mode method was better, and the detection limits of spectrophotometry, RGB visual method and fluorescence method were as low as 1.45 × 10 −1 copies/μL, 1.65 copies/μL and 1.58 × 10 −1 copies/μL, respectively. Compared with qPCR and ddPCR assays developed in previous studies, the dual-modality assay in this study had a lower detection limit. It was also independent of expensive qPCR and ddPCR equipment and the detection cost was low. Therefore, the colorimetric and fluorescent dual-modality assay represent a label-free and sensitive approach for assessing cf-mtDNA levels, offering promising implications for biomedical research and clinical diagnostics.
研究领域:
医学诊断
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2024
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IF 3.1
Chu Cheng,Qingzhou Cheng,Wei Zhou,Yulong Chen,Pengfeng Xiao
We proposed a single-color fluorogenic DNA decoding sequencing method designed to improve sequencing accuracy, increase read length and throughput, as well as decrease scanning time. This method involves the incorporation of a mixture of four types of 3’-O-modified nucleotide reversible terminators into each reaction. Among them, two nucleotides are labeled with the same fluorophore, while the remaining two are unlabeled. Only one nucleotide can be extended in each reaction, and an encoding that partially defines base composition can be obtained. Through cyclic interrogation of a template twice with different nucleotide combinations, two sets of encodings are sequentially obtained, enabling the determination of the sequence. We demonstrate the feasibility of this method using established sequencing chemistry, achieving a cycle efficiency of approximately 99.5 %. Notably, this strategy exhibits remarkable efficacy in the detection and correction of sequencing errors, achieving a theoretical error rate of 0.00016 % at a sequencing depth of ×2, which is lower than Sanger sequencing. This method is theoretically compatible with the existing sequencing-by-synthesis (SBS) platforms, and the instrument is simpler, which may facilitate further reductions in sequencing costs, thereby broadening its applications in biology and medicine. Moreover, we demonstrate the capability to detect known mutation sites using information from only a single sequencing run. We validate this approach by accurately identifying a mutation site in the human mitochondrial DNA.
研究领域:
分子生物学
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遗传学
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医学
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DOI
PubMed
高影响因子
CyTA-Journal of Food
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2020
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IF 1.653
Yongzhen Wang,Kai Zhu,Deguo Wang
The objective of this study was to develop a reliable visual method for rapid detection of donkey components to protect consumers from commercial adulteration. Six specific loop-mediated isothermal amplification (LAMP) primers targeted at donkey mitochondrial cytochrome b gene were designed, the mitochondrial DNA extraction simplified, the LAMP reaction system optimized, the specificity verified with mitochondrial DNA of horse, pork, cow, sheep, chicken, duck, and rabbit as negative controls, the detection limit determined with gradient dilution of adulterated meat with donkey meat, and the visual LAMP method for detection of donkey-derived ingredient in common meat products established. The results showed that the modified mitochondrial DNA extraction method was simple and repeatable, and the visual LAMP method with 4-(2-pyridylazo)-resorcinol sodium salt as indicator can accurately and specifically detect the donkey meat in common meat products, 1% detection limit. The study provided a promising solution for facilitating the surveillance of the commercial adulteration in processed meat.
研究领域:
食品科学
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分子生物学
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DOI
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-16
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IF 6.1
Xiong Yi,Chen Jiawen,Liang Wei,Li Kun,Huang Yingqi,Song Jingwen,Zhang Baoyu,Qiu Xiusheng,Qiu Dongbo,Zhang Qi,Qin Yunfei
Background Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated. Methods Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models. Results Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization. Conclusions The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury.
研究领域:
免疫学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2020
·Vol. 191
·期 3
·1340-1352
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IF 2.277
Su Yanbin,Sun Chengyu,Sun Xuwei,Wu Ruixue,Zhang Xing,Tu Yunzhou
The aim of this study was to explore whether or not acetylresveratrol as a potential substitute for resveratrol dragged the toxic aldehyde to inhibit the mutation of mitochondrial DNA. The results revealed that the acetylresveratrol shifted ultraviolet peak of trans -crotonaldehyde from 316 to 311 nm. In mitochondria, the acetylresveratrol split the ultraviolet peak at 311 nm of trans -crotonaldehyde into 311 nm and 309 nm; the aldehyde Raman band of trans -crotonaldehyde was red shifted by the acetylresveratrol from 1689 to 1686 cm −1 with obvious band decline; Raman bands at 1149 cm −1 , 1168 cm −1 , and 1325 cm −1 of acetylresveratrol disappeared. In aldehyde dehydrogenase, the aldehyde Raman band of trans- crotonaldehyde was red shifted by the acetylresveratrol from 1689 to 1684 cm −1 with band decline; Raman bands at 1150 cm −1 , 1168 cm −1 , and 1324 cm −1 of acetylresveratrol declined. The weak acidic microenvironment was the best, for the acetylresveratrol dragged the toxic aldehyde of trans -crotonaldehyde. Compared with the resveratrol, the effect of the acetylresveratrol on the toxic aldehyde of trans -crotonaldehyde was very similar to that of the resveratrol. The acetylresveratrol is very suitable as a potential substitute for resveratrol dragged the toxic aldehyde to inhibit the mutation of mitochondrial DNA.
In mitochondria, the Raman band of the toxic –CH=O of trans- crotonaldehyde (TCA) dragged by the Acetyl-Res from 1689 to 1686 cm −1 with obvious band decline, while the Raman bands at 1149 cm −1 , 1168 cm −1 , and 1325 cm −1 of the Acetyl-Res disappeared, respectively. The Acetyl-Res is very suitable as a potential substitute, for the Res dragged the toxic –CH=O of TCA to inhibit the mutation of mitochondrial DNA for anticancer.
研究领域:
生物化学
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分子生物学
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医学
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DOI
PubMed
高影响因子
MOLECULAR THERAPY
·
2023
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IF 12.4
Li Gao,Junsheng Zhang,Tingting Yang,Ling Jiang,Xueqi Liu,Sheng Wang,Xian Wang,Yuebo Huang,Huaying Wang,Mengya Zhang,Tingting Gong,Lijuan Ma,Chao Li,Chaoyong He,Xiao-ming Meng,Yonggui Wu
Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy and extracellular matrix accumulation in vivo and in vitro . These effects delayed CKD progression. Immunoprecipitation assays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.
研究领域:
肾病学
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免疫学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
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2024
·Vol. 15
·期 10
·1-10
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IF 8.1
Li Ming-Qiao,He Yu-Qi,Zhang Meng-Ni,Tang Wan,Tan Ya,Cheng Yue,Yang Mei,Zhao Nan,Li Ling,Yu Si-Rui,Li Ruo-Lan,Pan Qiong,Wu Ming-Yue,Chai Jin
Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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