ANALYST
·
2023
·Vol. 148
·期 18
·4346-4355
·
IF 4.2
Jiahai Wang,Cenlin Gui,Jianji Zhu,Baian Zhu,Zhuobin Zhu,Xiwen Jiang,Daqi Chen
Glass nanopore is an ideal candidate for biosensors due to its unique advantages such as label-free analysis, single-molecule sensitivity, and easy operation. Previous studies have shown that glass nanopores can distinguish different lengths of double-stranded DNA (dsDNA) at the same time with the length-resolution ability. Based on this, we proposed a novel design of a dsDNA block containing a programmable sensing site inside, which can be programmed to respond to different target molecules and cleaved into two smaller DNA blocks. When programming the sensing site with different sequences, for example, programming it as the substrate of GR-5 DNAzyme and CRISPR-Cas12a system, the DNA block could realize Pb2+ and cfDNA detection with the length-resolution ability of the glass nanopore. This strategy achieved a Pb2+ detection range from 0.5 nM to 100 nM, with a detection limit of 0.4 nM, and a BRCA-1 detection range from 1 pM to 10 pM, with a detection limit of 1 pM. The programable sensing site is easy to design and has strong expandability, which gives full play to the advantages of glass nanopore in length-resolution ability for dsDNA, and is expected to become an optional design for biosensing strategy for the glass nanopore as a biosensing platform.
研究领域:
生物传感器
·
分子生物学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2022
·Vol. 14
·期 5
·911-919
·
IF 1.067
Zhu Chunxia,Ming Shenqiu,Qiu Bin,Zhong Hui
FePt nanoparticles were in this study prepared at varied concentrations to assess their mechanism in regulating DNA injury and inactivation of Hela cells through mitogen-activated protein kinase (MAPK) signal pathway. The cells were divided into following 5 group sets: 1st, 2nd, 3rd,
4th and 5th, which were randomly intervened by following varied concentrations of FePt nanoparticles; 0, 5, 10, 15 and 20 μg/mL. Their action on cellular toxicity, proliferation and inactivation of cells was detected with CCK-8 method, while apoptotic condition was detected with
flow cytometry (FCM). The degree of DNA double chains fracture was detected with neutral single cell gel electrophoresis and immunofluorescence staining. The protein expressions of of EKR1/2, p-ERK1/2, p38 MAPK and p-p38 MAPK in every set were detected with Western Blot assay, while proliferative
activity in the 4th and 5th sets was lower than in the 1st set, and inhibiting action in the 4th set was best. There was no notable difference between 4th and 5th sets, and apoptotic rate in the 1st set was lower than in the other sets. The DNA percentage in the Hela cells was reduced and
Tial length was lengthened along with increased concentration of adopted FePt nanoparticles. The proliferation of Hela cells was restrained by FePt nanoparticles through restraining of the MAPK signal pathway, but growth of Hela cells was not affected, and DNA double-strand break (DSB) was
increased. The FePt nanoparticles could therefore be adopted as one kind of effective anti-tumor drug through increased DNA DSB in tumor cells based on killing effect of tumor cells and good compatibility for normal cells.
研究领域:
纳米技术
·
癌症生物学
·
细胞信号传导
·
毒理学
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Cong Ma,Kaiqin Hu,Xueke Zhang,Yaru Yu,Zuying Xu,Tian Ma,Hongzhen Ruan,Yingying Zhang,Jiajia Wang,Xinyu Yue,Chunmei Liang,Huifen Xiang,Rui Guo,Yunxia Cao,Zhiming Ding
Arsenic is a pollutant that can cross the placenta; however, research on the effects of arsenic exposure during pregnancy on the fertility of female offspring is limited. To address this gap, we developed a mouse model to investigate the relationship between arsenic exposure during pregnancy and fertility in female offspring. Our fertility assessment revealed that gestational exposure to 1 mg/kg arsenic or higher (10 mg/kg) resulted in reduction in litter size, ovarian volume, and multistage-follicle number in female offspring. By assessing the in vitro developmental capacity of oocytes and zygotes, we confirmed that the reduced fertility was due not to impaired oocyte quality but rather to a reduction in oocyte quantity. Arsenic exposure impedes synapsis formation in MPI and compromises homologous recombination-mediated repair of double-strand breaks, resulting in fewer crossovers. This disruption activates the pachytene-checkpoint, hindering the progression of the MPI and resulting in the elimination of defective oocytes through p-Chk2 activation. Our study reveals for the first time the detrimental effects of arsenic exposure during pregnancy on the fertility of female offspring, underscoring the urgent need to prevent such exposure to safeguard reproductive health.
研究领域:
生殖生物学
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毒理学
·
遗传学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
·
2024
·
IF 2.1
Tianying Liu,Qing Xie,Wenli Wang
Background Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation.Methods Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry.Results USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models.Conclusion In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.
研究领域:
肿瘤学
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放射生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2023
·Vol. 332
·期 6
·2093-2102
·
IF 1.6
Li Kehong,Fan Wenqi,Yan Jingxuan,Wang Jing,Zhao Peng,Liao Wei,Yang Yuchuan,Yang Xia,Wei Hongyuan,Chen Yue
Differences in cellular radiosensitivity and the binding affinity of radiopharmaceuticals could directly affect the radiotherapeutic effects. In this study, we investigated the radionuclide ( 177 Lu) induced radiosensitivity of serval non-small-cell lung cancer cells (NSCLCs) as well as the binding affinity of cetuximab to those cells. The apoptosis of NSCLCs caused by 177 Lu was related to the DNA double-strand damage and was cell-type dependent. We also proved that the introduction of 177 Lu to the antibody could enhance its cytotoxic effect on NSCLCs. The [ 177 Lu]Lu-DOTA-cetuximab could accumulate in the HCC827 tumor xenografts with excellent stability according to in vivo SPECT/CT imaging and the biodistribution results. The [ 177 Lu]Lu-DOTA-cetuximab showed high potential to be used for targeting diagnosis and radiotherapy in lung cancers.
研究领域:
肿瘤学
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放射生物学
·
核医学
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Long Wu,Shuhong Zhou,Yonghuan Yun,Lin Zhu,Bei Li,Weimin Zhang
Based on the exchange of the DNA duplex-quadruplex, a multifunctional Pb(II) ion probe was fabricated, in which Pb(II) ion-driven DNA duplexes act as a bridge to link CdSe/ZnS-luminol and Fe 3 O 4 nanoparticles . As Pb(II) ion owns a strong binding capacity for G-quadruplex (G4), it can unwind the DNA duplex and release its complementary strand. In this strategy, three detection modes, chemiluminescence (CL), fluorescence (FL) assay and colorimetric assay (CA), can be realized via DNA duplex bridged CdSe/ZnS and Fe 3 O 4 nanocomposites . Amongst, FL assay shows the best detection performance, and it exhibits a linear range of 10 nM to 10 µM, as well as the limit of detection (LOD) with 1.63 nM (n = 3, ± 3.5%). In the selective analysis, Pb(II) ion can be specifically detected in the nine different interfering metal ions . Besides, the magnetic probe requires only one “mixing and separation” operation and greatly improves the detection efficiency. The three assays can be combined as one method to achieve a simple and rapid feature. Such a three-in-one analytical platform, therefore, can serve as a powerful tool for selective, accurate and sensitive detection of Pb(II) ion.
研究领域:
生物化学
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分析化学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 8
·e2988
·
IF 5.965
Yan Siyuan,Liu Ling,Ren Fengxia,Gao Quan,Xu Shanshan,Hou Bolin,Wang Yange,Jiang Xuejun,Che Yongsheng
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ -H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Xu Ying,Lu Lunjie,Luo Judong,Wang Lili,Zhang Qi,Cao Jianping,Jiao Yang
The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both in vitro and in vivo. Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.
研究领域:
肿瘤学
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药理学
·
放射生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Xing-Yan Fu,Hao Yin,Xi-Tong Chen,Jing-Fang Yao,Yan-Nan Ma,Min Song,Huan Xu,Qian-Yao Yu,Shan-Shan Du,Yun-Kun Qi,Ke-Wei Wang
Oncolytic peptides represent promising novel candidates for anticancer treatments. In our efforts to develop oncolytic peptides possessing both high protease stability and durable anticancer efficiency, three rounds of optimization were conducted on the first-in-class oncolytic peptide LTX-315. The robust synthetic method, in vitro and in vivo anticancer activity, and anticancer mechanism were investigated. The D-type peptides represented by FXY-12 possessed significantly improved proteolytic stability and sustained anticancer efficiency. Strikingly, the novel hybrid peptide FXY-30, containing one FXY-12 and two camptothecin moieties, exhibited the most potent in vitro and in vivo anticancer activities. The mechanism explorations indicated that FXY-30 exhibited rapid membranolytic effects and induced severe DNA double-strand breaks to trigger cell apoptosis. Collectively, this study not only established robust strategies to improve the stability and anticancer potential of oncolytic peptides but also provided valuable references for the future development of D-type peptides-based hybrid anticancer chemotherapeutics.
研究领域:
癌症研究
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Haowei Fu,Xiaofang Zhu,Qiannan Di,Jiahui Sun,Qianqian Jiang,Qian Xu
Di(2-ethyl-hexyl) phthalate (DEHP), an environmental endocrine disruptor, can destroy the sperm genomic integrity and impairs spermatogenesis. N6-methyladenosine (m6A) is involved in the cellular effects of DEHP. However, the genotoxic effect of DEHP on spermatocytes and the possible role of m6A in this process remain unclear. This study demonstrated that m6A alleviates DEHP genotoxicity in GC-2 cells. In DEHP-treated mice, DNA double-strand breaks (DSBs) were induced in the testis and spermatocytes. To further explore the molecular mechanism of DEHP genotoxicity on spermatocytes, GC-2 cells were exposed to DEHP. DEHP produced distinct genotoxicity and caused DSBs, which led to the inhibition of DNA synthesis and cell cycle arrest. The DNA damage response (DDR) was initiated to repair the DSBs induced by environmentally relevant levels of DEHP (100 μM and 200 μM). During this process, METTL3 upregulated m6A, which facilitated the DDR via stabilizing the DNA damage repair factors ( Rad51 and Xrcc5 ) mRNA to maintain the pro-survival state. Moreover, Mettl3 knockdown partially inhibited DDR. Interestingly, high-dose DEHP (400 μM and 600 μM) directly induced apoptosis rather than the pro-survival state. Altogether: METTL3-mediated m6A participates in maintaining the pro-survival state by upregulating DDR, providing guidance for mitigating the genotoxicity of environment-related level DEHP exposure.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Baolin Chen,Xun Wang,Xia Gao,Jie Jiang,Mancheng Hu,Shuni Li,Quanguo Zhai,Yucheng Jiang
In this work, TiO 2 nano particle was used for two purposes: it played as a role of a solid carrier for immobilization of HRP, and meanwhile acted as a photo-catalyst itself. In this way, the loss of enzymatic activity during enzyme immobilization can be compensated by the coupling of TiO 2 photo-catalysis. Then, the surface of TiO 2 nanoparticles were modified by phase-transitioned lysozyme (PTL) and connected with horseradish peroxidase (HRP) via a DNA helix ( [email protected] 2 ). The DNA double helix chain was utilized as a flexible spacer arm to keep the flexibility of the immobilized enzyme. The [email protected] 2 showed a high recovered activity (90.52%) of the original activity of free HRP. This data is better than most reported activity recovery of immobilized enzyme. Moreover, [email protected] 2 can maintain high catalytic activity, stability and reusability when degrading phenol in wastewater. The phenol of 0.5 mmol∙L −1 could be totally degraded within 10 min. Moreover, a visual colorimetric method for phenol concentration by [email protected] 2 was established, and the phenol concentration of 0–0.2 mmol∙L −1 can be visually detected with naked eyes. Furthermore, an enzymatic-photocatalytic synergetic effect of [email protected] 2 is found and investigated. The efficiency of [email protected] 2 ensures it a potential application in the wastewater treatment.
研究领域:
环境科学
·
化学工程
·
生物技术
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2020
·Vol. 16
·期 16
·1906915
·
IF 11.459
Chengyan Wang,Jiani Xie,Xinghua Dong,Linqiang Mei,Maoru Zhao,Zhengwei Leng,Houxiang Hu,Lele Li,Zhanjun Gu,Yuliang Zhao
The exploration of an old drug for new biomedical applications has an absolute predominance in shortening the clinical conversion time of drugs for clinical application. In this work, carbon nanoparticles suspension injection (CNSI), the first clinically approved carbon nanoparticles in China, is explored as a new nano-radioprotective agent for potent intestinal radioprotection. CNSI shows powerful radioprotective performance in the intestine under oral administration, including efficient free radical scavenging ability, good biosafety, high chemical stability, and relatively long retention time. For example, CNSI shows high reactive oxygen species (ROS) scavenging activities, which effectively alleviates the mitochondrial dysfunction and DNA double-strand breaks to protect the cells against radiation-induced damage. Most importantly, this efficient ROS scavenging ability greatly helps restrain the apoptosis of the small intestinal epithelial and crypt stem cells, which decreases the damage of the mechanical barrier and thus relieves radiation enteritis. Moreover, CNSI helps remove the free radicals in the intestinal microenvironment and thus maintain the balance of intestinal flora so as to mitigate the radiation enteritis. The finding suggests a new application of clinically approved carbon nanoparticles, which not only promotes the development of new intestinal radioprotector, but also has a great potential for clinical transformation.
研究领域:
纳米技术
·
辐射生物学
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）