Chemistry-An Asian Journal
·
2018
·Vol. 13
·期 18
·2611-2618
·
IF 3.692
Huan Feng,Qingtao Meng,Yue Wang,Chengchen Duan,Cuiping Wang,Hongmin Jia,Zhiqiang Zhang,Run Zhang
Graphical Sensing and imaging of hypochlorous acid (HOCl) : A new responsive fluorescence probe, PQI , is reported for quantitative fluorescence detection of HOCl in aqueous solution and live organisms. Visualisation of HOCl in live cells and in vivo sensing and imaging of HOCl in zebrafish and nude mice were achieved by using PQI as the fluorescence probe. The development of effective bioanalytical methods for rapid, sensitive and specific detection of HOCl in vitro and in vivo plays a key role for better understanding the roles of this molecule in normal and diseased conditions, but remains challenging due to the highly reactive nature of HOCl and the complicated biological conditions. In this work, a new fluorescence probe, PQI , was developed for monitoring of the HOCl level in biological samples. PQI was easily synthesized by a one-step condensation reaction. Upon addition of HOCl, significant changes in the absorption spectra and the color of the solution were noticed, facilitating the “naked eye” detection of HOCl in PBS buffer. The fluorescence of PQI was found to be significantly increased within a few seconds, leading to “OFF-ON” fluorescence response towards HOCl. The sensing mechanism, oxidation of thioether by HOCl, was confirmed by HRMS titration analysis. PQI features a large Stokes shift, high sensitivity and selectivity, and rapid fluorescence response towards HOCl. Quantitative detection of HOCl in single live cells was demonstrated through fluorescence imaging and flow cytometry analysis. PQI was then successfully used in visualisation of HOCl in live zebrafish and nude mice.
研究领域:
生物化学
·
分析化学
·
医学影像
✓ 已验证
DOI
PubMed
高影响因子
Journal of Cancer
·
2021
·
IF 4.207
Yong-Zhi Lun,Jie Sun,Ben Liu,Wen Dong,Ling-Hong Pan,Jian Lin,Jing-Xia Zhang
Objective: As targeted drugs, exogenous serpins could be introduced to patients to restore body balance. This study aimed to observe further the inhibitory effects of recombinant Hespintor (a Kazal-type serpin) combined with Sorafenib on transplanted human hepatoma tumors in nude mice specimens and to explore the possible transcriptional regulation by Hespintor. Methods: A model of human hepatoma tumors transplanted in nude mice was established, and the medication was administrated to observe the growth of the tumors. Four weeks after the drug administration, the tumors were removed to evaluate the inhibition effects of Hespintor on in-situ tumor growth and liver metastasis. The expression levels of MMP2, MMP9, Bax, Bcl-2, and caspase-3 in the tumor organizations were detected with Western blot. The target genes of the Hespintor were screened based on tissue RNA-Seq, and the regulatory network was constructed. Results: It was found that the recombinant Hespintor displayed a significant antitumor effect on the subcutaneous growth of MHCC97-H cells. Moreover, the therapeutic effects of the combination therapy were significantly better than those of single therapy. 10 target genes with significantly different expression by Hespintoron tumor tissue were identified. Finally, a visual regulatory networkwas constructed for target mRNA-pathway. Conclusions: The antitumor effect of Hespintor combined with Sorafenib in treating the subcutaneously implanted hepatocellular carcinoma tumors in nude mice was significant. The possible transcriptional regulation by Hespintor involved multiple signaling pathways, and it was not just the antitumor effect of uPA via its extracellular inhibitions.
研究领域:
肿瘤学
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分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
·
2020
·
IF 1.892
Jing Dong,Yuelei Chen,Wenhui Yang,Xi Zhang,Lin Li
Breast cancer is a high incidence disease in humans. Artemisinin is an important extract that is widely used as an antimalarial drug which also serve as effective treatments for cancer. 32 nude mice were injected with 0.2 ml of MDA-MB-231 cell suspension of 2 × 10 7 cells/ml respectively. The nude mice models were randomly divided into four groups of 8 in each group. Each group was given daily gavage, high dose group: 200 mg/kg/0.1 ml, middle dose group 100 mg/kg/0.1 ml, low dose group 50 mg/kg/0.1 ml, control group: 0.1 ml vegetable oil was fed continuously for 21 days. ELISA was used to detect serum vascular endothelial growth the content of factor VEGF and hypoxia-inducible factor HIF-1α were detected. The expression of Notch pathway-related factors in tumor tissue was detected by fluorescence quantitative assay. ELISA results showed that the serum VEGF decreased significantly in the high dose group compared with the control group ( p < .01), while the other dose groups did not have significant ( p > .05). The serum HIF-1α in the high dose group compared with the control group, the decrease in HIF-1α was significant ( p < .05), and the other groups were not significant ( p > .05). The result of fluorescence quantitative section showed that artemisinin could down-regulate the expression of notch signaling related factors notch1, Dll4 and Jagged1, and 200 mg/kg dose group had the most significant effect. It may inhibit the development of tumors by reducing serum angiogenesis-related factors VEGF, HIF-1ɑ and inhibiting the activity of notch1 signaling pathway related factors.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Yongda Wang,Zheng Hu,Jia Li,Yunhan Zhao,Meng Kou,Feng Qin,Zhiguo Zhang
A dual-excitation laser modulation technique for the sensitive measurement of photosensitizers in tumor is proposed. The technique is based on the difference in optical absorption properties of photosensitizers and biological tissues at 405 nm and 450 nm. The 405 nm and 450 nm laser beams, with the same modulation frequency and 180° phase difference, were coupled into a single fiber simultaneously. A periodic signal with a frequency of 1 kHz was generated in alternating excitation, and was processed by phase sensitive detectors. The weak photosensitizer fluorescence masked by tissue autofluorescence can be effectively separated through the proposed method, so that the final signal intensity is only related to the concentration of photosensitizer. The method with a sensitivity of 0.22 mL/ng was determined by measuring the low concentration of protoporphyrin IX (PpIX) solution, and the detection limit of instrument reached 0.5 ng/mL. The puncturable optical probe with a diameter of 675 µm ensures that PpIX in can be detected with spatial resolution, which was performed in the measurement of PpIX in tumor bearing nude mice .
研究领域:
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 6
·749-755
·
IF 1.128
Lou Huadong,Liu Xiaoling,Xu Xinyan,Liu Weizhen
Cyclophosphamide is a common clinical anticancer drug that can produce various toxic side effects during cancer treatment. This is an urgent difficulty of current clinical medications that needs to be overcome. With the advancement and development of science and technology, the advent
of nanomaterials will help improve the accuracy and safety of anticancer drugs. This study explored the effect of cyclophosphamide-containing nanoapoliposomes on retinoblastoma cells. HXO-Rb44 and WERI-Rb-1 cells were treated cyclophosphamide-containing nanoapoliposomes at different concentrations.
The Cell Counting Kit-8 (CCK-8) was used to detect cell multiplication, a Transwell assay was used to detect cell immigration and invasion, flow cytometry was used to detect cell apoptosis and the cell cycle, and Western blotting was used to detect Bax, Bcl2, caspase3, and cyclin D1 expression.
In addition, a live nude mouse model was generated to detect the effect of cyclophosphamide-containing nanoapoliposomes on the growth of retinoblastoma cells in vivo. Cyclophosphamide-containing nanoapoliposomes dramatically restricted the multiplication, migration, and invasion of
HXO-Rb44 and WERI-Rb-1 cells, promoted cell apoptosis, and inhibited cell-cycle progression compared with the control. Finally, cyclophosphamide-containing nanoapoliposomes significantly inhibited the growth of RB cells in nude mice. These data showed that cyclophosphamide-containing nanoapoliposomes
had an inhibitory effect on retinoblastoma cells.
研究领域:
肿瘤学
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药剂学
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分子生物学
✓ 已验证
DOI
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2022
·Vol. 132
·期 4
·297-311
·
IF 3.688
Yu Liao,Kejun Hu,Wangwang Liu,Wei Wang,Huanhuan Qiu,Shumin Pan,Qi Lv,Guanglin Xu
Hepatocellular carcinoma (HCC) is one of the principle causes of cancer-associated death throughout the world. However, the patients with HCC are insensitive to traditional drugs and lack effective therapeutic drugs. Dysregulation of Hippo-Yes-associated protein (YAP) signalling is closely associated with HCC. Bortezomib (BTZ) is mainly used in clinical multiple myeloma. It has recently been confirmed that BTZ could suppress cell proliferation in many different types of cancer. Nevertheless, the precise effects of BTZ on HCC and its possible interactions with the Hippo-YAP signalling pathway in HCC cells remain largely unknown. In this study, HCC cell lines (HepG2 and Huh7) and nude mice with xenograft tumours were used to evaluate the influences of BTZ. Furthermore, we focused on exploring whether BTZ exerts its anti-HCC effect through the Hippo-YAP signalling pathway and aimed to lay a theoretical foundation for BTZ as a potential therapeutic drug for HCC. Herein, our results disclose a new mechanism of BTZ in controlling the cell growth of HCC. BTZ downregulates the level of YAP by promoting LATS1 expression to inhibit the growth of HCC cells, which leads to the phosphorylation of YAP and limits YAP nuclear translocation. In sum, our data confirmed that the Hippo-YAP signalling pathway mediates the anti-HCC effects of BTZ.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Man Ding,Xuechen Zhang,Jiangying Shi,Kaili Cui,Ruipeng Yang,Fengming Liu,Shuhua Shan,Ghani Israr,Zhuoyu Li
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion. Quinoa is a dicotyledonous plant, and the quinoa bran is the outer seed coat of quinoa. Functional molecules in plants play an important role in the treatment and alleviation of chronic diseases. In this study, quinoa bran was used as the raw material. The active components with an anti-colorectal cancer effect were extracted by acetone and separated with an AB-8 macroporous resin column, which was further identified as terpenoids by liquid-mass spectrometry (LMS), named Quinoa bran terpenoids (QBT). The yield of quinoa bran terpenoids was 0.77%. Moreover, the results showed that QBT significantly inhibited the proliferation of colorectal cancer cells DLD-1 and HCT-8 with a concentration gradient dependent manner. Respectively, the IC 50 values of DLD-1 and HCT-8 cells were 0.42 ± 0.02 and 0.54 ± 0.05 mg/mL. Further studies showed that QBT upregulated apoptosis-related proteins such as activated-caspase-3, 8, and 9. In addition, QBT decreased mitochondrial membrane potential , promoted the expression of the pro-apoptotic protein Bax, and inhibited the anti-apoptotic protein Bcl-2. The experiments showed that QBT significantly repressed the growth of tumors in nude mice . In conclusion, these results indicated that QBT largely inhibits the development of colorectal cancer to large extent through upregulation of caspase-3, 8, and 9 and reduction of mitochondrial membrane potential, and has great potential for anti-tumor progression.
研究领域:
肿瘤学
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药理学
·
植物科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Wenmin Chen,Yue Wu,Chuanyu Yang,Wenlong Ren,Lei Hou,Huichun Liang,Tingyue Wu,Yanjie Kong,Jiao Wu,Yu Rao,Ceshi Chen
Breast cancer is one of the most prevalent malignancies affecting women worldwide, underscoring the urgent need for more effective and specific treatments. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy to develop new lead compounds by selectively targeting oncoproteins for degradation. In this study, we designed, synthesized and evaluated a CRBN-based PROTAC, L055, which targets CDK9. Our findings demonstrate that L055 effectively inhibits the proliferation, induces cell cycle arrest, and decreases the survival of ERα-positive breast cancer cells in vitro. L055 specifically binds to CDK9, facilitating its degradation via the CRBN-dependent proteasomal pathway. Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ERα-positive breast cancer and potentially other malignancies.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2024
·Vol. 40
·期 1
·1-18
·
IF 5.3
Yang Ye,He Runze,Li Dongxiao,Mu Tianli,Kuang Ziteng,Wang Min
Zinc finger protein 384 (ZNF384) is a highly conserved transcribed gene associated with the development of multiple tumors, however, its role and mechanism in serous ovarian cancer (SOC) are unknown. We first confirmed that ZNF384 was abnormally highly expressed in SOC tissues by bioinformatics analysis and immunohistochemistry. We further used lentivirus packaging and transfection techniques to construct ZNF384 overexpression or knockdown cell lines, and through a series of cell function experiments, gradually verified that ZNF384 promoted a series of malignant behaviors of SOC cell proliferation, migration, and invasion. By establishing a xenotransplantation model in nude mice, it was confirmed that ZNF384 promoted the progress of SOC in vivo. Mechanistically, Overexpression of ZNF384 enhanced the transcriptional activity of Lin-28 homolog B (LIN28B), which promoted the malignant behavior of SOC cells. In addition, LIN28B could regulate the expression of the downstream factor ubiquitin D (UBD) in SOC cells, further promoting the development of SOC. This study shows that ZNF384 aggravates the malignant behavior of SOC cells through the LIN28B/UBD axis, which may be used as a diagnostic biomarker for patients with SOC. Graphical abstract
研究领域:
肿瘤学
·
分子生物学
·
遗传学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2022
·
IF 9.221
Chao Zhao,Fangyuan Zhou,Kai Lu,Shikui Yang,Baojin Tan,Wanlu Sun,Lina Shangguan,Hai-Yan Wang,Yi Liu
Acetylcholinesterase (AChE) plays an important role in the process of chemotherapy drug-induced cell apoptosis and is also an apoptosis marker to diagnose disease and assay the effect of the drug. Thus, we designed and synthesized a novel near-infrared fluorescent probe (NFL-SF) to detect AChE activity, which contained near-infrared (NIR) fluorophore NFL-OH and 2-thienylformyl chloride as the recognition unit. The probe has higher specificity and sensitivity to AChE and excellent biocompatibility. With the increasing concentration of AChE, the probe displayed an enhanced fluorescence signal at 745 nm for 30 min, with the detection limit of 0.2 mU/mL. In addition, NFL-SF not only detected exogenous AChE activity, but also effectively monitored the endogenous AChE activity of chemotherapeutic drug-induced cell apoptosis in living cells. When the AChE activity was inhibited with donepezil , the fluorescence intensity of the NIR channel was significantly reduced. Notably, the probe was successfully applied to in vivo imaging of nude mice . We believe that this probe could provide a strategy for rapidly and visually monitoring AChE activity.
研究领域:
生物医学工程
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 24
·5406-5415
·
IF 7
Junzhe Fu,Weijiang Yu,Xuedan Qian,Youxiang Wang,Jian Ji
Carbon monoxide (CO) is regarded as a promising therapeutic agent for chemotherapy sensitization. To simultaneously achieve controllable in situ CO production and efficient chemotherapeutics delivery is of great significance. Here, we presented a polyvinylpyrrolidone (PVP) core–shell microneedle (MN) system that encapsulated the effervescent component, photocatalyst, and doxorubicin hydrochloride (Dox·HCl) for CO-sensitized chemotherapy. Upon the insertion of MNs, the effervescent component, composed of sodium bicarbonate and tartaric acid, was exposed to interstitial fluid, leading to the burst release of carbon dioxide (CO2). The generated gas not only enhanced the diffusion of Dox·HCl but also served as a substrate for the photocatalytic generation of CO. From the experimental results, the photocatalyst CuS atomic layers (CAL) displayed an effective CO2 photoreduction performance, which could realize an irradiation time/intensity-dependent CO-controlled release. Ex vivo permeation studies demonstrated that effervescent CO2 production markedly enhanced the intradermal diffusion of Dox·HCl. Eventually, the robust antitumor efficacy of this versatile MN platform was proved in B16F10-bearing nude mice. This CO-sensitized chemotherapeutic MN system offered a novel strategy for transdermal gas/drug delivery, which might provide a new direction in tumor suppression.
研究领域:
药学
·
生物医学工程
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Cen Zhao,Dawei Yang,Yuchen Ye,Zhenzhong Chen,Tifan Sun,Jiawei Zhao,Kai Zhao,Na Lu
Multiple myeloma (MM) is a malignancy of antibody-producing plasma cells with genomic instability and genetic abnormality as its two hallmarks. Therefore, DNA damage is pervasive in MM cells, which indicates irregular DNA damage response (DDR) pathway. In this study, we demonstrated that LT-171-861, a multiple kinase inhibitor , could inhibit proliferation and induce apoptosis in MM cells. LT-171-861 promoted DDR pathway and triggered DNA damage through impeding the process of homologous recombination in double strand breaks, rather than directly elevating ROS level in MM cells. Mechanism research revealed that Pim2 inhibition was responsible for LT-171-861-indcued DNA damage and cell apoptosis. LT-171-861 mainly suppressed Pim2 kinase activity and reduced the expression of its phosphorylated substrates, such as 4EBP1 and BAD. Moreover, Olaparib , a PARP inhibitor , could enhance the antitumor effect of LT-171-861 in suppressing tumor growth in MM xenografted nude mice . Taken together, our results demonstrated that LT-171-861 showed a promising therapeutic potential for MM and had an additional lethal effect with PARP inhibitors.
研究领域:
癌症生物学
·
分子生物学
·
药理学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
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