Analytical Methods
·
2021
·Vol. 13
·期 5
·712-718
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IF 2.896
Jing Liu,Tianze Wang,Bo Xiao,Muhan Deng,Peng Yu,Taiping Qing
The breast cancer 1 (BRCA1) gene is a tumor suppressor gene, whose mutation is closely related to breast cancer. Therefore, the sensitive detection of the BRCA1 gene is extremely important for human health, particularly for women. In this study, a label-free fluorescent method based on hairpin DNA-templated copper nanoclusters (CuNCs) was for the first time developed for the detection of the BRCA1 gene. In the absence of target DNA, the detection system showed a strong red emission and produced a high emission peak. However, in the presence of the BRCA1 gene, the DNA probe hybridized with the BRCA1 gene and conformation of the DNA probe changed. As a result, the amount of produced CuNCs decreased and a low emission peak was obtained. The fluorescence intensity of the detection system was linearly correlated with the concentration of the BRCA1 gene ranging from 2 nM to 600 nM. The detectable limit was 2 nM for the BRCA1 gene assay, which was comparable with those reported by other non-amplifying sensors. Moreover, the developed method showed satisfactory recoveries for the BRCA1 gene assay in the bovine serum. The DNA-templated CuNC-based fluorescent assay thus offered a promising platform for the diagnosis of a breast cancer biomarker.
研究领域:
分子生物学
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癌症研究
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纳米技术
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2024
·Vol. 10
·期 1
·1-11
·
IF 6.1
Zhao Wenpeng,Zhou Liwei,Zhao Wentao,Yang Huiying,Lu Zhenwei,Zhang Liang,Zhang Yaya,Xie Yuanyuan,Lu Hanwen,Han Wanhong,He Jiawei,Qiu Xiansheng,Jia Fang,Zhao Wujie,Zhang Bingchang,Wang Zhanxiang
Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, the clinical use of TMZ is limited by its various side effects and resistance to chemotherapy. The present study revealed the synergistic inhibition of glioblastoma through the combined administration of TMZ and perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in the suppression of DNA repair mechanisms. Furthermore, the combination of TMZ and perifosine elicited caspase-dependent apoptosis, decreasing glioblastoma cell viability and proliferation. The observed synergistic effect of this combination therapy on glioblastoma was validated in vivo, as evidenced by the substantial reduction in glioblastoma xenograft growth following combined treatment with TMZ and perifosine. In recurrent glioma patients, higher BRCA1 expression is associated with worse prognosis, especially the ones that received TMZ-treated. These findings underscore the potent antitumor activity of the AKT inhibitor perifosine when combined with TMZ and suggest that this approach is a promising strategy for clinical glioblastoma treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Italian Journal of Animal Science
·
2021
·
IF 2.217
Yi Ma,Mawda Elmhadi,Chao Wang,Hao Zhang,Hongrong Wang
Several studies have demonstrated that high-concentrate (HC) diet with thiamine supplementation can alleviate rumen epithelium inflammation and protecting the barrier function in goats. This study aimed to investigate the effects of dietary supply of thiamine on mitophagy and endoplasmic reticulum stress (ERS) during high-concentrate diet feeding. Twenty-four Boer goats (35.62 ± 2.4 kg) were used in this study, goats were subsequently assigned to 3 treatment groups (8 goats in each group) as follows: a low-concentrate diet (CON; concentrate: forage 30:70), a high-concentrate diet (HC; concentrate: forage 70:30) and high-concentrate diet with 200 mg thiamine/kg DMI (HCT; concentrate: forage 70:30) for 12 weeks. Compared with the HC group, the goats of HCT group had a markedly higher final weight, net weight gain, and average daily gain (ADG). The blood physiological and biochemical results showed that the HCT group expressed a lower the content of lymphocytes and leukocytes but a higher total protein and monocytes compared with that of HC group. The rumen epithelial mitochondrial membrane potential change (ΔΨm), relative mitochondrial DNA (mtDNA) content, adenosine triphosphate (ATP) level, together with the activities of the respiratory complexes I, III, and IV were markedly higher in the HCT group relative to HC ones. Relative to the HC group, the unc-51 like autophagy activating kinase 1 (ULK1), microtubule-associated protein 1 light chain 3 (LC3), autophagy-related 5 (ATG5), autophagy related 7 (ATG7), Beclin1, PTEN induced putative kinase 1 (PINK1), PERK (PKR-Endoplasmic Reticulum Kinase), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), X-box binding protein 1 (XBP1), heat shock 70 kDa protein 5 (HSPA5), DNA damage-inducible transcript 3 (DDIT3) and DNA damage-inducible transcript 4 (DDIT4) mRNA levels were decreased, but the breast cancer 1 (BRCA1), ataxia telangiectasia mutated (ATM), heat shock factor binding protein 1 (HSBP1) were increased in rumen epithelium of the HCT group. The results of transmission electron micrographs showed that the cell structure of the HCT group was higher integrity than that in the HC group, and the damage degree of mitochondria as well as endoplasmic reticulum being lower than the HC group. These results demonstrated that dietary thiamine could enhance rumen epithelial integrity by suppressing the responses of ERS and mitophagy during long-term HC diet feeding.HIGHLIGHTSThis study is the first to demonstrate that the reduction of inflammatory response is related to the down-regulation of autophagy and endoplasmic reticulum stress in goats.Thiamine has good anti-inflammatory and anti-oxidation properties, which can be applied in intensive industry to reduce the negative effects caused by long-term high-concentrate diet.
研究领域:
动物营养
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分子生物学
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兽医学
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营养基因组学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Shunzhe Zheng,Meng Li,Wenqian Xu,Jiaxin Zhang,Guanting Li,Hongying Xiao,Xinying Liu,Jianbin Shi,Fengli Xia,Chutong Tian,Ken-ichiro Kamei
The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.
研究领域:
癌症研究
·
药学
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纳米技术
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Ni Hui,Xiaotian Sun,Shuyan Niu,Xiliang Luo
Biofouling arising from nonspecific adsorption is a substantial outstanding challenge in diagnostics and disease monitoring, and antifouling sensing interfaces capable of reducing the nonspecific adsorption of proteins from biological complex samples are highly desirable. We present herein the preparation of novel composite nanofibers through the grafting of polyethylene glycol (PEG) polymer onto polyaniline (PANI) nanofibers and their application in the development of antifouling electrochemical biosensors. The PEGylated PANI (PANI/PEG) nanofibers possessed large surface area and remained conductive and at the same time demonstrated excellent antifouling performances in single protein solutions as well as complex human serum samples. Sensitive and low fouling electrochemical biosensors for the breast cancer susceptibility gene (BRCA1) can be easily fabricated through the attachment of DNA probes to the PANI/PEG nanofibers. The biosensor showed a very high sensitivity to target BRCA1 with a linear range from 0.01 pM to 1 nM and was also efficient enough to detect DNA mismatches with satisfactory selectivity. Moreover, the DNA biosensor based on the PEGylated PANI nanofibers supported the quantification of BRCA1 in complex human serum, indicating great potential of this novel biomaterial for application in biosensors and bioelectronics.
研究领域:
材料科学
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生物传感器
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生物医学工程
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电化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）