Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Xin Wei,Mingzhu Zuo,Qiongwen Liang,Shiwei Zhang,Jingmei Wang,Zhanfeng Li,Wenguang Yang,Fang Ma,Wangxiao He,Tianya Liu
Microsatellite-stable colorectal cancer (MSS-CRC) is characterized by poor immune infiltration and immune evasion, leading to rapid tumor progression and limited efficacy of current immunotherapies. The bioinformatics analysis revealed that the hyperactivation of the Wnt/β-catenin signaling pathway in MSS-CRC is instrumental in mediating immune suppression. Although inhibiting this pathway presents a therapeutic opportunity, no Wnt inhibitors have been clinically approved due to Wnt's essential role in maintaining tissue homeostasis, with inhibition in normal cells causing significant toxicity. To address it, we discovered that Wnt activation in colorectal cancer cells enhances macropinocytosis, particularly favoring the uptake of glycosylated proteins to meet increased nutrient demands. Building on this insight, we developed a glycosylated human serum albumin (GHSA) co-assembled with carnosic acid (CA), termed glycosylated human serum albumin-carnosic acid (GHSACA), which is selectively internalized by Wnt-activated colorectal cancer cells. This approach not only reduces off-target toxicity but also effectively inhibits the Wnt pathway, resulting in notable tumor inhibition and immune reactivation in murine models, while maintaining a favorable safety profile. This strategy offers a promising therapeutic solution by combining selective Wnt inhibition with enhanced immune activation in MSS-CRC, and highlights the potential of leveraging disease-specific cellular uptake mechanisms for designing nanomedicines, advancing the development of precision-targeted cancer therapies.
研究领域:
肿瘤学
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免疫治疗
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分子生物学
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纳米医学
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生物信息学
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药理学
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产品关联
DOI
高影响因子
iScience
·
2022
·
IF 6.107
Fanyang Lv,Yuhua Zhan,Wei Lu,Xiubin Ke,Yahui Shao,Yiyuan Ma,Juan Zheng,Zhimin Yang,Shanshan Jiang,Liguo Shang,Yao Ma,Lei Cheng,Claudine Elmerich,Yongliang Yan,Min Lin
Summary Bacteria of the genus Pseudomonas consume preferred carbon substrates in nearly reverse order to that of enterobacteria, and this process is controlled by RNA-binding translational repressors and regulatory ncRNA antagonists. However, their roles in microbe-plant interactions and the underlying mechanisms remain uncertain. Here we show that root-associated diazotrophic Pseudomonas stutzeri A1501 preferentially catabolizes succinate, followed by the less favorable substrate citrate, and ultimately glucose. Furthermore, the Hfq/Crc/CrcZY regulatory system orchestrates this preference and contributes to optimal nitrogenase activity and efficient root colonization. Hfq has a central role in this regulatory network through different mechanisms of action, including repressing the translation of substrate-specific catabolic genes, activating the nitrogenase gene nifH posttranscriptionally, and exerting a positive effect on the transcription of an exopolysaccharide gene cluster. Our results illustrate an Hfq-mediated mechanism linking carbon metabolism to nitrogen fixation and root colonization, which may confer rhizobacteria competitive advantages in rhizosphere environments.
研究领域:
微生物学
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植物科学
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分子生物学
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DOI
PubMed
高影响因子
CANCER BIOLOGY & THERAPY
·
2020
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IF 3.659
Chunhua Zhou,Wencheng Kong,Tongfa Ju,Qi Xie,Lulu Zhai
Background Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman’s correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR.Results We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic.Conclusion MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.
研究领域:
肿瘤学
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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
Molecular & Cellular Toxicology
·
2022
·
IF 1.718
Li Hua,Guo Junyu,Qin Zhongwei,Wei Mingwei,Guo Houji,Huang Fuda
Background Emerging evidence has indicated that circular RNAs (circRNAs) play vital roles in colorectal cancer (CRC). CircRNA leucine zipper and EF-hand containing transmembrane protein 1 (circLETM1) have been found to be ectopic in CRC, but their role in CRC has not been studied yet. Objective This study aims to explore the roles of circLETM1 in CRC and the possible molecular mechanism. Result The results showed that circLETM1 was highly expressed in CRC cells, and was localized at the cytoplasm. Functional assays verified that overexpression of circLETM1 could facilitate, but circLETM1 downregulation could hamper proliferation, migration and invasion abilities of CRC cells. In addition, mechanism assays found that circLETM1 absorbed and reduced microRNA (miR)-143-3p expression to promote keratin 80 (KRT80). Rescue experiments proved that circLETM1 mediated CRC proliferation, migration and invasion through KRT80. Conclusion Taken together, our results suggested that circLETM1 promotes proliferation, migration and invasion through the miR-143-3p/KRT80 axis in CRC. Therefore, targeting circLETM1 may provide a novel option for CRC treatment.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Yuan-yuan Zhai,Qiang Wang,Qi-yao Nong,Mei-yu Gao,Ying Zhang,Qin-wen Xiao,Yuan Tian,Zun-jian Zhang,Feng-guo Xu,Pei Zhang
Multidrug resistance (MDR) is a significant challenge in cancer treatment, with limited effective strategies available. Neuropilin-1 (NRP1) is emerging as a potential therapeutic target for overcoming drug resistance, but its role in MDR and the identification of potential inhibitors require further exploration. In this study, we investigated the role of NRP1 in MDR and identifies potential inhibitors targeting NRP1. Elevated NRP1 expression was observed in oxaliplatin (OXP)-resistant HCT116 (HCT116/L) and cisplatin (DDP)-resistant A549 cells (A549/DDP). Virtual screening and biological assays identified pitavastatin (Ptv) as a potent NRP1 inhibitor that restored chemosensitivity in resistant cells both in vitro and in vivo . Mechanistic studies revealed that Ptv directly binds to NRP1, promotes degradation of Zinc finger X-chromosomal protein (ZFX), and disrupts the NRP1-ZFX axis to reverse MDR. This study provides promising prospects for targeting the NRP1-ZFX axis as a therapeutic strategy for MDR and highlights the potential clinical application of Ptv in diseases involving NRP1.
研究领域:
癌症生物学
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药理学
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分子生物学
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肿瘤学
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药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yaru Wang,Yanting Li,Xin Li
Background This study compared the effect of ultrasound microbubble-mediated miR-503–5p downregulation with that of pure liposome-mediated miR-503–5p downregulation on colorectal cancer (CRC) progression and explored the downstream mechanism. Methods Bioinformatics tools were utilized to predict miR-503–5p-targeted genes and CRC progression-associated genes. MiR-503–5p and sal-like 1 (SALL1) expressions in CRC cells and tissues were analyzed by qRT-PCR and/or bioinformatics tools; their correlations with overall survival and clinicopathological features of CRC patients were presented, and their interaction was validated by dual-luciferase reporter assay. CRC cells received ultrasound microbubble-mediated miR-503–5p downregulation and/or liposome-mediated miR-503–5p downregulation or SALL1 silencing. Cell phenotype changes were evaluated by flow cytometry, as well as MTT, Wound healing, Transwell and tube formation assays. E-cadherin, N-cadherin, Vimentin , B-cell lymphoma (Bcl)− 2, Cleaved caspase-3, and SALL1 expressions in cells were analyzed by Western blot . Results Upregulated miR-503–5p in CRC tissues and cells was detected, associated with poorer cell differentiation , easier lymph node metastasis and higher TNM stages, and related to poorer prognoses of CRC patients. Ultrasound microbubble-mediated miR-503–5p downregulation relative to pure liposome-mediated miR-503–5p downregulation better decreased viability, inhibited migration, invasion and tube formation, enhanced apoptosis, upregulated SALL1, E-cadherin and Cleaved caspase-3, and downregulated miR-503–5p, N-cadherin, Vimentin and Bcl-2 in CRC cells. SALL1 was targeted by miR-503–5p, low-expressed in CRC tissues and cells and positively related to CRC patients’ survival. Silencing SALL1 exerted the opposite effects, which reversed the effects of ultrasound microbubble-mediated miR-503–5p downregulation and vice versa. Conclusion Ultrasound microbubble-mediated miR-503–5p downregulation suppressed in vitro CRC progression via promoting SALL1 expression.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Weishan Zhuge,Jiayang Kuang,Keke Kuang,Meilin Rao,Dan Jian,Haizhen Lin,Zijun Li,Shaotang Li,Yihu Zheng,Namki Cho,Xiaokun Li,Ri Cui
Background Colorectal cancer (CRC) is among the most prevalent malignancies globally, with its incidence continuing to rise in recent years. Sorafenib, a multi-kinase inhibitor, has shown therapeutic effects in advanced CRC. Usenamine A (UD32-3), a natural compound, is isolated from lichens. However, anti-tumor activity of UD32-3 in CRC and its biological functions in anti-CRC activity of sorafenib remain unknown. Purpose This study aims to elucidate the mechanism underlying anti-CRC effects of UD32-3 and its potential to enhance the therapeutic efficacy of sorafenib. Study design and Methods Immunofluorescence assays were employed to investigate reactive oxygen species (ROS) and autophagy levels. Gene knockdown or overexpression was performed using Lipofectamine 3000 reagent, and relative gene and protein expression levels were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot analyses. Molecular docking analysis was performed to investigate the interaction between UD32-3 and superoxide dismutase 2 (SOD2). Mouse xenograft models were employed to evaluate the effects of combination therapy with UD32-3 and sorafenib. Results UD32-3 exerts anti-CRC activity by inducing ROS-mediated autophagy and inhibiting YAP pathway through targeting SOD2. Knocking down SOD2 sufficiently induced ROS generation and autophagy, and inhibited the YAP pathway, thereby enhancing the anti-CRC activity of UD32-3. Conversely, overexpression of SOD2 yielded opposite results, attenuating these effects. Combined treatment with UD32-3 and sorafenib exerted synergistic anti-tumor activities by activating autophagy and inhibiting YAP signaling pathway. Additionally, YAP inhibitor strengthened anti-CRC activity of UD32-3 and sorafenib by inhibiting SOD2 expression, suggesting autophagy-mediated negative feedback loop between SOD2 and YAP. Conclusions UD32-3 has significant druggable potential, and combination treatment of UD32-3 and sorafenib may serve as an effective therapeutic strategy for patients with certain CRC.
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
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IF 3.8
Xu Miaowen,Zhang Dong,Li Tianran,Zhuang Yanwen,Wang Zixun,Zhang Xudong,Zhang Zhaohan,Chen Lepeng,Xu Qiong,Qian Yayun,Li Limao
This study developed a nanozyme-SERS dual-function sensor that exhibits both highly efficient peroxidase (POD)-like activity and superior surface-enhanced Raman spectroscopy (SERS) enhancement, designed for detecting homocysteine (Hcy) in serum from colorectal cancer (CRC) patients. Bimetallic Au@Pt nanoparticles (Au@Pt NPs) exhibited exceptional nanozyme catalysis and SERS performance, enabling the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to oxidized TMB (oxTMB) with a pronounced SERS signal generation. Au@Pt NPs were assembled into aminated capillaries via electrostatic adsorption and subsequently modified with Hcy aptamers to create the nanozyme-SERS dual-function sensor. When Hcy was present, the reducing thiol groups (-SH) consumed the hydroxyl radicals (·OH) produced by the decomposition of H 2 O 2 . This inhibited the oxidation of TMB, resulting in a weaker SERS signal. The SERS sensor demonstrated a remarkably low detection limit (LOD) for Hcy, reaching as low as 0.14 × 10⁻ 12 mol/L. Furthermore, within the concentration range of 10⁻ 12 to 10⁻ 4 mol/L, there was a linear relationship between the logarithm of Hcy concentration and the SERS signal intensity. Serum samples from both healthy individuals and CRC patients were tested with the SERS sensor. The results demonstrated a high degree of concordance with those obtained by the enzyme-linked immunosorbent assay (ELISA), showing significantly higher Hcy levels in CRC patient serum compared to healthy controls. Unlike traditional methods such as colorimetric assays, fluorescence analysis, and the SERS “sandwich” strategy, which often involve complex procedures and have low sensitivity, this approach offers a simple, highly sensitive, and specific method for detecting Hcy. It holds promise as an effective tool for early CRC diagnosis.
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2026
·
IF 10.2
Xi Yu,Yujie He,Jiani Zhong,Yue Li,Yuan Zhu,Yingying Chen,Jingbo Yin,Zeting Yuan,Peihao Yin
Colorectal cancer (CRC) management is significantly hindered by the challenges of early detection and the high rates of recurrence and metastasis following surgery. Systemic postoperative therapies are frequently compromised by adverse effects and drug resistance. To address this, we engineered a localized and combinatorial platform by integrating Bufalin (BU), a potent anti-tumor agent from traditional Chinese medicine, into citric acid-based carbon dots modified with hyaluronic acid (BU-CDs CA-HA ), which were subsequently incorporated into a Janus-structured membrane. This design enabled robust adhesion to post-resection tumor sites, ensuring sustained local drug release and spatially confined photothermal/photodynamic therapy (PTT/PDT) while effectively sparing adjacent healthy tissues from thermal damage. Upon near-infrared (NIR) irradiation, the synergistic BU-PTT/PDT action induced potent immunogenic cell death (ICD), as evidenced by the release of damage-associated molecular patterns (DAMPs), thereby initiating a systemic anti-tumor immune response. Concurrently, BU down-regulated heat shock proteins (HSPs) and HIF-1α expression, leading to the suppression of tumor PD-L1 and effectively countering immune escape. In orthotopic and metastatic CRC mouse models, this multifunctional Janus membrane system demonstrated remarkable efficacy in preventing local recurrence and distant metastasis. This outcome was attributed to the concerted effect of immediate cytotoxic ablation and the elicited durable anti-tumor immunity. Our work presents a novel biomaterial-based strategy that enhanced the efficacy and safety of postoperative CRC treatment, offering a versatile platform for site-specific combination therapy.
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·Vol. 17
·期 1
·84-91
·
IF 2.7
Miaowen Xu,Gaoyang Chen,Yong Huang,Hangyu Song,Zheng Wu,Fengjuan Jiang,Lei Fu,Caili Bi,Xiaowei Cao,Wei Wei
This paper presents functionalized magnetic nanoparticles (Fe3O4@Au MNPs) combined with the surface-enhanced Raman spectroscopy (SERS) technique for sensitive detection of colorectal cancer (CRC) protein biomarker carbohydrate antigen 19-9 (CA19-9). Fe3O4@Au MNPs were constructed by the PEI-mediated seed growth method. Then, the signal molecule 5-5′-dithiobis (succinimidyl-2-nitrobenzoic acid) was used as a bridging agent to link CA19-9 antibody, and the SERS sensor was prepared. Using this sensor, detection of CA19-9 can be realized with only a one step sampling reaction. Fe3O4@Au MNPs combine the advantages of magnetic materials and noble metal nanoparticles, effectively amplifying the signal by creating numerous “hot spots” within the Au particle gaps and enhancing magnetic enrichment. Consequently, this approach lowers the detection limit (LOD) and enhances detection sensitivity. The ratio of characteristic peak intensities I1392/I1069 was selected for calculation, and a linear equation was constructed with a LOD as low as 0.27 U mL−1 by quantitative detections of the standard antigen. Finally, the sensor was used to analyze the clinical serum samples from CRC patients and healthy individuals, and the detection results were consistent with the actual results. This method exhibits notable advantages, including simplicity, high sensitivity, specificity, stability and reproducibility. It is expected to provide a new promising analytical method for clinical CA19-9 immunoassay.
研究领域:
生物医学工程
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肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2025
·Vol. 15
·期 23
·1754
·
IF 4.3
Shiwen Liu,Xin Zhang,Jihui Wang,Xuan Chen,Xiaoqin Pan,Junqiu Zhang,Jingyu Xu,Weibin Bai
Colorectal cancer (CRC) is the third most common malignant tumor worldwide, with morbidity and mortality rates increasing annually. Consequently, the development of safe and effective natural anti-tumor drugs has become a critical research focus. Lignin, a polyphenolic polymer abundant in nature, possesses a unique chemical structure that imparts antioxidant, anti-inflammatory, and tumor cell-related bioactivities, demonstrating remarkable potential in the prevention and treatment of CRC. In this study, we investigated the anti-tumor cell effects of coffee grounds lignin nanoparticles (CLN), prepared using aqueous ethanol extraction from coffee waste, against three CRC cell lines (HCT116, HT29, SW620). The results indicated that CLN potently inhibited the proliferation of all three CRC cell lines mentioned above. This research supports the transformation of lignin from natural products into innovative anti-colorectal cancer agent, offering new insights for the development of novel therapeutic strategies characterized by low toxicity and high efficacy. As research advances and technology continues to innovate, lignin-based nanoparticles emerge as key natural products in CRC therapy, offering new hope for patients and paving the way for the application of natural products in cancer therapy.
✓ 已验证
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 175
·期 15
·3111-3130
·
IF 6.81
Siming Yu,Linna Li,Wei Tian,Dan Nie,Wei Mu,Fang Qiu,Yu Liu,Xinghan Liu,Xiaofeng Wang,Zhimin Du,Wen-Feng Chu,Baofeng Yang
Background and Purpose PEP06, a polypeptide modified from endostatin, was investigated for its antitumour effects on colorectal cancer (CRC) and the possible mechanisms of this antitumour activity were examined in in vitro and in vivo models. Experimental Approach After PEP06 treatment, cell proliferation and migration assays were performed in CRC cells. Epithelial–mesenchymal transition (EMT) progression was determined by Western blotting, immunofluorescent staining and immunohistochemistry in vitro and in a residual xenograft model. MiRNAs regulated by PEP06 were identified by miRNA microarray and verified by in situ hybridization and quantitative real-time PCR. The interactions between PEP06 and integrin αvβ3 were determined with Biacore SA biochips. The cellular function of miR-146b-5p was validated by gain-of-function and loss-of-function approaches. A mouse model of lung metastasis was used to determine the effect of PEP06 on metastatic growth. Key Results PEP06 did not affect cell viability but reduced migration and EMT in SW620 and HCT116 cells. PEP06 significantly repressed the expression of miR-146b-5p in these two cell lines through binding to integrin αvβ3. MiR-146b-5p was shown to increase EMT by targeting Smad4, and the miR-146b-5p-Smad4 cascade regulated EMT in CRC. PEP06 also suppressed CRC pulmonary metastasis, increased survival of mice and hampered residual tumour growth by inhibiting EMT through down-regulating miR-146b-5p. Conclusions and Implications PEP06 is a polypeptide that inhibits the growth and metastasis of colon cancer through its RGD motif binding to integrin αvβ3, thereby down-regulating miR-146b-5p to inhibit EMT in vitro and in vivo . It might have potential as a therapeutic for CRC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 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）