TALANTA
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2022
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IF 6.556
Xin Gao,Haoran Xu,Zhuoyi Ye,Xin Chen,Xin Wang,Qi Chang,Yueqing Gu
The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, making it one of the most lethal forms of cancer. Early-stage diagnosis and resection of the incipient lesions could increase the 4-year survival rate of PA up to 78%. Platelet-derived growth factor receptor β (PDGFRβ), an oncogenic key regulator for migration, proliferation and angiogenesis of cancer cells, has been proved to be aberrantly expressed in the majority of PA. Herein, by amino acid substitution strategy and surface plasmon resonance (SPR) analysis, we designed a novel PDGFRβ-targeting peptide (YQGX-10) with high affinity ( K d = 227.7 nM) and coupled it with a near-infrared fluorescent (NIRF) dye MPA for precisely detection of PA. Great binding affinity and specificity were displayed in a series of in vitro assays. NIRF imaging experiments demonstrated that the synthesized probe could be highly accumulated in xenograft and orthotopic BxPC-3 tumors and provide favorable tumor contrast in the mice, offering a potential novel approach for the early diagnosis of PA. Moreover, YQGX-10 could visualize tumor boundaries and minor lesions in BxPC-3 xenograft mice, shedding a new light on NIRF-guided tumor resection of PA. In addition, we successfully constructed the radioactive probe 99m Tc-HYNIC-YQGX-10 for the diagnosis of PA with high specificity and sensitivity. In summary, the probe warrants further exploration for clinical translation in the early diagnosis and NIRF-guided surgery of PA.
研究领域:
肿瘤学
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分子影像学
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生物医学工程
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Wendi Wang,Qing Han,Tianwei Wang,Jian Liu,Qingbin Ni,Jingyi Sun,Ying Wang,Baoliang Sun
Ischemic stroke (IS) has a high mortality rate. Multiplexed detection of IS core biomarkers is of great significance to early diagnosis and personalized treatment of IS patients. Whether pericytes, a key component of the neurovascular unit and blood-brain barrier located on the capillary wall, could serve as a promising biomarker for IS is to be explored. Herein, we observed a significant upregulation of inflammatory and apoptotic factors, such as MMP9, in pericytes subjected to in vitro ischemia. By transfecting pericytes with ASK1-shRNA to inhibit ASK1 expression, we noted reduced levels of inflammatory and apoptotic markers, including MMP9, as well as enhanced pericyte contraction and migration, thereby preserving the integrity of the blood-brain barrier. Additionally, ELISA assays conducted using plasma samples from patients with varying NIHSS scores revealed statistically significant concentrations of PDGFRβ and MMP9. Furthermore, we developed a highly sensitive and specific quantitative detection method for PDGFRβ and MMP9 based on fluorescence sensor technology. This novel detector exhibits high sensitivity, repeatability, and stability, enabling precise dual detection. Thus, the results suggest the great potential of the detection of PDGFRβ and MMP9 for early diagnosis of IS and prognosis prediction of the disease.
研究领域:
神经科学
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医学
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分子生物学
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PubMed
高影响因子
BMC CANCER
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2023
·Vol. 23
·期 1
·1-13
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IF 3.8
Liu Bin,Zheng Xin,Li Jiajun,Yao Peng,Guo Peng,Liu Wei,Zhao Gaoping
Background Colorectal cancer is a common malignant tumour. Invasive growth and distant metastasis are the main characteristics of its malignant biological behaviour, and they are also the primary factors leading to death in colon cancer patients. Atovaquone is an antimalarial drug, and its anticancer effect has recently been demonstrated in several cancer models in vitro and in vivo, but it has not been examined in the treatment of colorectal cancer. Methods To elucidate the effect of atovaquone on colorectal cancer. We used RNA transcriptome sequencing, RT‒PCR and Western blot experiments to examine the expression of NF-κB (p-P65), EMT-related proteins and related inflammatory factors (IL1B, IL6, CCL20, CCL2, CXCL8, CXCL6, IL6ST, FAS, IL10 and IL1A). The effect of atovaquone on colorectal cancer metastasis was validated using an animal model of lung metastases. We further used transcriptome sequencing, the GCBI bioinformatics database and the STRING database to predict relevant target proteins. Furthermore, pathological sections were collected from relevant cases for immunohistochemical verification. Results This study showed that atovaquone could inhibit colorectal cancer metastasis and invasion in vivo and in vitro, inhibit the expression of E-cadherin protein, and promote the protein expression of N-cadherin, vimentin, ZEB1, Snail and Slug. Atovaquone could inhibit EMT by inhibiting NF-κB (p-P65) and related inflammatory factors. Further bioinformatics analysis and verification showed that PDGFRβ was one of the targets of atovaquone. Conclusion In summary, atovaquone can inhibit the expression of NF-κB (p-P65) and related inflammatory factors by inhibiting the protein expression of p-PDGFRβ, thereby inhibiting colorectal cancer metastasis. Atovaquone may be a promising drug for the treatment of colorectal cancer metastasis.
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高影响因子
Cancer Cell International
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2025
·Vol. 25
·期 1
·1-18
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IF 6
Li Duo,Zhong Qi,Xiao Di,Wang Weifan,Xie Lejing,Peng Mei,Xu Cangcang,Wu Huaying,Li Zhuan,Yang Xiaoping
Background Hepatocellular carcinoma (HCC) is an invasive malignant tumour for which few effective treatment options are currently available. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases used for the treatment of patients with advanced HCC. Although lenvatinib has been proven effective in treating HCC patients, clinical data show that the response rate to lenvatinib is very low and that 76% of HCC patients are insensitive to lenvatinib. Phenformin is a well-known activator of adenosine monophosphate-activated protein kinase (AMPK), which has recently attracted widespread attention because of its anticancer effects. We investigated whether phenformin could enhance the efficacy of lenvatinib in treating HCC and, if so, the underlying mechanisms involved in this process. Methods The anticancer effects of the combination of phenformin and lenvatinib in HCC cells were assessed in vitro and in vivo. First, colony formation, EdU and MTT assays were conducted to measure the viability of the HCC cells. Flow cytometry was used to assess the cell cycle distribution of HCC cells. Then, western blotting (WB) was performed to detect protein expression in HCC cells after various treatments. Immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) assays were used to determine the interaction relationships of proteins. In addition, a xenograft model was used to analyze the effects of the different treatments on the proliferation of HCC cells. Immunohistochemistry and western blot assays were conducted to investigate the expression of related proteins in the tissues of the xenograft model. Haematoxylin and eosin (H&E) staining was used to analyze the toxicity to the livers and kidneys of mice. Western blot assays were used to detect protein expression in human HCC samples. Results High expression of platelet-derived growth factor receptor β (PDGFRβ) resulted in the insensitivity of HCC cells to lenvatinib, and PDGFRβ knockdown increased the sensitivity of HCC cells to lenvatinib. Phenformin inhibited the proliferation of HCC cells via AMPK-mediated PDGFRβ degradation. Compared with lenvatinib monotherapy, combined treatment with phenformin and lenvatinib considerably enhanced the anticancer effects both in vivo and in vitro. Mechanistic studies showed that AMPK binds PDGFRβ and promotes its degradation via the c-Cbl-mediated lysosomal pathway. Conclusions Our study reports a novel combined therapy using phenformin and lenvatinib, which can increase the sensitivity of HCC cells to lenvatinib via AMPK-mediated PDGFRβ degradation. Hence, this treatment strategy may provide a personalized approach for treating HCC patients with high PDGFRβ expression and facilitate the development of basic and clinical research on the use of lenvatinib for the treatment of HCC.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Hanchun Yan,Wei Wang,Xinhua Song,Yaqi Wang,Zhaowen Nie,Honghan Zhang,Hao Duan,Ningyuan Li,Yuqi Feng,Yuhui Zhang,Chao Wang,Zhongchun Liu
Background The underlying mechanisms of major depressive disorder (MDD) remain unclear; however, increasing evidence has linked MDD to blood–brain barrier (BBB) dysfunction. This study aimed to determine whether BBB impairment represents an early pathological change during chronic stress and whether preservation of BBB integrity is associated with attenuation of neuroinflammatory and behavioral abnormalities. Methods We employed a time-course (1, 2, and 4 weeks) chronic unpredictable mild stress (CUMS) model in C57BL/6 J mice. Depressive-like behaviors (SPT, FST, TST, OFT), BBB permeability (Evans blue), tight junction (TJ) protein expression (qPCR, Western Blot), ultrastructure (TEM, IF), peripheral and central inflammatory responses (ELISA, qPCR, IF), and transcytosis-related changes (Western Blot, TEM) were systematically assessed at each time point. In separate intervention experiments, the PDGFRβ inhibitor Imatinib (50 mg/kg/d) or an MMP-9 inhibitor (20 mg/kg/d) was administered throughout the 4-week CUMS procedure. Results Depressive-like behaviors became robustly established by week 4. In contrast, BBB disruption occurred earlier: molecular changes (e.g., Claudin-5 protein loss) were significant at week 1, followed by functional permeability, TJ structural disruption, increased endothelial vesicle density, and inflammatory alterations at week 2. This pathology worsened by week 4. The 4-week Imatinib co-treatment attenuated the development of depressive-like behaviors, alleviated BBB disruption, and reduced neuroinflammatory abnormalities. At the molecular level, CUMS induced a time-dependent upregulation of MMP-9. Imatinib treatment attenuated activation of the PDGFRβ/MMP-9 pathway, whereas MMP-9 inhibition preserved BBB integrity and attenuated central inflammatory abnormalities despite persistently elevated peripheral cytokine levels. Conclusion BBB dysfunction is an early pathological event during chronic stress and is associated with both tight junction disruption and transcytosis-related alterations. Pharmacological preservation of BBB integrity was accompanied by reduced neuroinflammation, consistent with BBB integrity being an important modulator of chronic stress-associated central inflammatory abnormalities. The PDGFRβ/MMP-9 pathway may represent a promising mechanism associated with stress-related BBB injury and a potential therapeutic target.
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高影响因子
ULTRASOUND IN MEDICINE AND BIOLOGY
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2024
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IF 2.4
Han-mei Li,Lin-li Feng,Qiong Jiang,You Yang,Ju-ying Zhang,Xia Luo,Xing Yang,Bo Ren,Li-tao Ye,Zheng-ju Hou,Yang Li,Jin-hong Yu
Objective As a reversible condition at its early stages, liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, underscoring the importance of early detection for preventing severe outcomes and improving prognosis. To address this issue, we developed a platelet-derived growth factor receptor β (PDGFRβ)-targeted nanoscale phase-change contrast agent to target activated hepatic stellate cells (aHSC) and enable ultrasound imaging as a foundation for the early evaluation of liver fibrosis. Methods PDGFR-β antibody-modified phase-change contrast agents (PPCAs) were synthesized utilizing film hydration and ultrasonic emulsification with perfluoropentane (PFP) encapsulated. PPCAs were specifically conjugated to aHSC with high PDGFR-β expression, whose targeting ability was evaluated using fluorescence confocal microscopy and flow cytometry. Phase transition at different temperatures and mechanical indices (MIs), as well as contrast-enhanced ultrasound imaging were analyzed. Results PPCAs had an average diameter of 283.6 ± 11.3 nm with good dispersibility and relative stability, and the echo intensity increased correspondingly with increasing MIs. PPCAs exhibited both excellent biocompatibility and imaging ability when excited by high-frequency ultrasound set to an MI of 1.0 at 37°C, and simultaneously showed strong specific targeting ability to aHSC, with cellular uptake reaching 56.67 ± 5.96%. Conclusion As a new imaging avenue, PPCAs have the potential to enhance ultrasound imaging and establish the basis for diagnosis by targeting aHSC specifically with good biocompatibility and stability.
研究领域:
医学影像学
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肝病学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
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