MOLECULAR IMMUNOLOGY
·
2024
·
IF 3.2
Zhou Si Yun,Song Zhihua,Tian Xuelian,Xia Min,Hu Rongjing,Luo Mei
Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.
研究领域:
免疫学
·
微生物学
·
药理学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Lei,Guoguo Wan,Xiaoyu Geng,Jianguo Sun,Yi Zhang,Jianwei Wang,Congwen Yang,Zheng Pan
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo ( L . rotata ), a Tibetan medicinal plant , is used to treat “yellow-water diseases”, such as skin disease, jaundice and rheumatism . Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown. Aim of the study To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. Materials and methods The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions. Results IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-κB signaling pathway during wound injury in vivo and in vitro . IGLR suppressed the inflammatory cytokines iNOS, IL-1β and TNF-α in the early stage of wound healing . During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-β and α-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). Conclusion IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing.
研究领域:
药理学
·
免疫学
·
伤口愈合
·
植物科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Results in Chemistry
·
2025
·
IF 4.2
Qikai Liu,Yaqi Mao,Yujie Jiao,Ru Li,Binghua Mian,Peili Li,Jiali Lei,Yang Liu
With the rapid development of intensive aquaculture systems, the widespread misuse of antibiotics has raised significant ecological and human health concerns. However, effective methods for antibiotic removal in recirculating aquaculture systems (RAS) remain scarcely reported. This study systematically constructed three distinct degradation systems - photocatalytic (P), photoelectrocatalytic (PE), and photoelectrocatalytic coupled with chlorine (PE-Cl − ) - based on TiO 2 nanotube arrays for efficient tetracycline hydrochloride (TCH) degradation in RAS. Results demonstrated that the PE-Cl − system exhibited superior TCH degradation efficiency, following first-order reaction kinetics. Key operational parameters were optimized, revealing that NaCl concentration (optimal at 30 mM) and acidic conditions (pH = 3, achieving 97.5 % degradation) significantly enhanced system performance, while humic acid (HA), sodium acetate (SA), and actual aquaculture water showed minimal interference. Radical quenching experiments identified hydroxyl radicals (•OH) as the predominant reactive species contributing to TCH degradation. The degradation pathways primarily involved demethylation, hydroxylation, and deamination reactions. Importantly, toxicity assessment using Chlorella vulgaris indicated significantly reduced ecotoxicity of the degradation byproducts ( p < 0.001). This study provides both theoretical foundations and practical solutions for addressing persistent organic pollutants in RAS, offering valuable insights for sustainable aquaculture water treatment.
研究领域:
环境科学
·
水产养殖学
·
污染控制
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Genetics
·
2025
·
IF 2.8
Minglu Zhang,Jianbo He,Rao Fu,Guojian Bao,Yijun Lu,Zechuan Zhang,Jiawu Yan,Jialu Ding,Fei Yang,Beicheng Sun
Introduction: Small nucleolar RNA (snoRNA) mediates RNA modifications, including 2′-O-methylation (Nm) and pseudouridine (Ψ), which has been proven to impact tumor progression. However, the role of snoRNA in the epigenetics of tumors remains poorly understood due to the lack of sufficiently effective experimental methods to identify snoRNA targets. Here, we identified SNORD13H, a C/D box snoRNA, as being downregulated in hepatocellular carcinoma (HCC), and its low expression was associated with HCC development.Methods: To elucidate specific roles of SNORD13H in HCC, we used a comprehensive array of methodologies, including flow cytometry, xenograft mouse model, reverse transcription at low dNTP concentration followed by PCR (RTL-P) assay, and surface sensing of translation (SUnSET) assay.Results: In this study, we first demonstrated that reduced SNORD13H serves as a biomarker for HCC, facilitating cellular proliferation. SNORD13H mediates 2′-O-methylations of 18S rRNA and RAS mRNA, thereby enhancing translation efficiency and regulating RAS protein levels in HCC. The diminution of SNORD13H activates the RAS pathway, contributing to the progression of HCC.Discussion: Our study establishes SNORD13H as a dual-function regulator in HCC progression. Furthermore, our findings indicate that SNORD13H is detectable in plasma, highlighting its potential utility in tumor screening.
研究领域:
分子生物学
·
癌症研究
·
遗传学
·
表观遗传学
·
RNA修饰
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2024
·
IF 3.9
Zhou Meng,Duan Xiujie,Jin Tao,Feng Xibing,Liu Ying,Wang Shuo,Feng Jiankang,Zhang Mengtong,Chai Tiantian,Mao Boneng,Shao Shihe,Jin Guofan
Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF 3 - o, m, p- phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF 3 . The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2 μg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug. Graphical abstract
研究领域:
药物化学
·
肿瘤学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Wen Shuai,Huan Xiao,Panpan Yang,Yiwen Zhang,Faqian Bu,Yongya Wu,Qiu Sun,Guan Wang,Liang Ouyang
The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.
研究领域:
肿瘤学
·
药理学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2021
·
IF 4.013
Yuanyuan Wu,Mengnan Zeng,Ruiqi Xu,Beibei Zhang,Shengchao Wang,Benke Li,Yuxuan Kan,Bing Cao,Xiaoke Zheng,Weisheng Feng
Background Melanoma is an aggressive cancer with a rapidly increasing incidence rate worldwide. Acteoside has been shown to have antitumor effects in multiple human cancers; however, the underlying function and mechanisms of acteoside in melanoma remain unclear. Purpose This study explored the inhibitory effect of acteoside on melanoma and the possible mechanisms. Methods Acteoside (15 mg/kg, 30 mg/kg) was administered to mice daily for 21 days. ICI182,780 (0.5 mg/kg) was intraperitoneally injected 30 min before acteoside administration three times a week to evaluate whether the effects elicited by acteoside were mediated via the estrogen receptor . Tumor growth and metabolism, cardiac function, ROS and apoptosis levels in the spleen, serum inflammatory factors, and immune cells in the spleen were monitored. STAT3 , p-STAT3, CD31 , and survivin levels in tumor tissues were measured via immunofluorescence. Ras, Raf1, STAT3, p-STAT3, Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9 levels in tumor tissues were determined via Western Blotting . Results The results showed that acteoside inhibited melanoma growth, alleviated inflammation levels in mice, attenuated ROS and apoptosis levels in the spleen, downregulated the levels of CD31, survivin, Ras, Raf1, p-STAT3, and Bcl-2, and upregulated the levels of ER β , Bax, cleaved caspase-3, and cleaved caspase-9. Moreover, the effect of acteoside was blocked by ICI182,780. Conclusion Acteoside may promote the apoptosis of tumor cells by regulating the ER β -Ras/Raf1-STAT3 signaling axis, thus inhibiting the occurrence and development of melanoma.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
·
IF 3.5
Zhou Fengfeng,Li Chenglin,Che Fengyuan
To explore the effect of Licochalcone A on cuproptosis in glioma and the underlying mechanism, U87 MG and U251 cells were treated with 10, 20, and 30 µM Licochalcone A for 24 h. Key assays including immunofluorescence, TEM, mitochondrial membrane potential and morphological analysis, as well as other cuproptosis-related indexes were detected. Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used. An in vivo nude mouse xenograft model was established. Our results demonstrated that Licochalcone A triggered cuproptosis in a dose-dependent manner, and in U87 and U251 cells, 30 µM Licochalcone A treatment increased the Cu²⁺ accumulation by 2.86 ± 0.67 folds and 1.96 ± 0.39 folds, elevated pyruvic acid levels by 2.15 ± 0.23 folds and 2.57 ± 0.46 folds, reduced mitochondrial membrane potential by 34.13 ± 1.70% and 40.43 ± 9.05%, downregulated the protein expression of FDX1 and LIAS, and increased cellular ROS levels by 4.74 ± 0.85 folds and 5.10 ± 2.16 folds, respectively. These changes were accompanied by obvious mitochondrial swelling and cristae disruption, resulting in a significant inhibition of cell proliferation. Mechanistically, it promoted cuproptosis by inactivating RAS/ERK. In vivo, 10 mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.
✓ 已验证
DOI
PubMed
高影响因子
CANCER BIOLOGY & THERAPY
·
2023
·
IF 3.6
Xiaojing Xing,Xuguang Wang,Meichen Liu,Qianxue Guo,Hongyue Wang
A GTPase binding protein, Ras interacting protein 1 (RASIP1), has been reported with a tumor-promoting role in lung cancer cells, and its role in lymphoma remains unknown. The analysis of medical databank shows that RASIP1 is upregulated in diffuse large B-cell lymphoma (DLBCL) specimens. In this article, we demonstrated that RASIP1 is highly expressed in DLBCL cell lines, compared with primary B cells. The gain- and loss-of-function experiments were performed to investigate the effects of RASIP1 on DLBCL cells. CCK-8, flow cytometry, western blot, and transwell assays demonstrated that silence of RASIP1 inhibited proliferation, cell cycle transition, and invasion and induced significant apoptosis in DLBCL cells, and ectopic expression of RASIP1 played opposite roles. Xenograft results revealed that RASIP1 facilitated the growth of DLBCL cells in vivo. These findings suggest that RASIP1 may be required for malignancy of DLBCL cells. In addition, we also found that the expression of RASIP1 was negatively regulated by forkhead box O3 (FOXO3), which has been reported to suppress the proliferation of DLBCL cells. Our results indicate that FOXO3 is bound to the promoter sequence of RASIP1 and inhibits its transcription. The suppressive effects of FOXO3 on proliferation and invasion of DLBCL cells were neutralized by RASIP1. In conclusion, we demonstrate that FOXO3 negatively regulated RASIP1 facilitates growth and invasion of DLBCL cells, provides novel diagnostic markers and therapeutic targets for DLBCL in clinic.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2013
·
IF 4.387
Ying Chen,Mengli Yang,Yun Xiang,Ruo Yuan,Yaqin Chai
Single nucleotide polymorphisms are the most common type of genetic variations among human beings and can serve as biomarkers for various types of diseases. In this work, based on ligase chain reaction amplification for the production of massive hemin/G-quadruplex DNAzymes to quench the electrochemiluminescent (ECL) emission of quantum dots (QDs), a universal and sensitive single nucleotide polymorphism detection method is described. During the ligase chain reaction process, the mutant K-ras target gene is recycled and exponentially duplicated, leading to the attachment of numerous G-rich sequences on the QD-embedded sensing surface. Upon the addition of the assistant sequences and hemin, numerous hemin/G-quadruplex DNAzymes are formed, which consume the dissolved oxygen in the detection buffer and result in significant quenching of QD ECL emission for sensitive single nucleotide polymorphism determination. The developed method shows a linear range of 50 fM to 50 pM and an estimated detection limit of 45 fM for the mutant K-ras gene. The proposed strategy also exhibits high selectivity towards the mutant K-ras gene against the co-existence of 10 3 -fold excess of the wild-type K-ras gene, which makes our method a useful addition to the alternatives for single nucleotide polymorphism monitoring.
研究领域:
分子生物学
·
医学诊断
·
生物传感技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Cell International
·
2026
·
IF 7
Ni Jie,Gao Aidi,Chen Ying,He Chao,Wang Xixi,Savelyeva Natalia,Dong Xin,Wang Yiqiang,Wang Mu
Background Despite significant advances in the treatment of clear cell renal cell carcinoma (ccRCC) over the past two decades, therapeutic intervention for patients at advanced or metastatic stages remains a clinical hurdle. Emerging evidence highlights aberrant CD70 expression during tumor progression, supporting its potential as a therapeutic target in advanced ccRCC. However, the molecular mechanisms underlying CD70-mediated metastatic processes remain poorly defined. Methods CD70 was knocked out or overexpressed in three ccRCC cell lines, and its role in tumor progression was assessed using in vitro migration and invasion assays, as well as in vivo tumorigenesis and metastasis models . Mass spectrometry-based proteomics was performed to identify differentially expressed proteins and potential pathway dysregulation following CD70 depletion. Co-immunoprecipitation (Co-IP) assays confirmed the CD70-NF1 interaction, and NF1 knockdown in CD70-knockout cells was conducted to reverse the effects of CD70 depletion on Ras/ERK signaling, migration, invasion, and epithelial-mesenchymal transition (EMT)-related features. Expression of EMT-related marks were evaluated by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). Results CD70 was significantly upregulated in ccRCC tissues and correlated with poor survival outcomes. CD70 knockout markedly inhibited in vitro cell migration and invasion, as well as in vivo tumor growth and metastasis. Mechanistically, CD70 depletion was associated with increased neurofibromin 1 (NF1) expression in ccRCC cells; CD70 knockout resulted in robust NF1 induction, which in turn suppressed Ras/ERK signaling and downstream EMT-related molecular alterations. Notably, NF1 knockdown largely reversed the inhibitory effects of CD70 knockout on these key molecular and functional phenotype changes. Conclusions Our findings uncover a novel CD70-NF1-Ras/ERK axis that contributes to ccRCC progression and metastasis, involving suppression of NF1 and subsequent activation of the Ras/ERK signaling pathway, which further promotes EMT and enhances metastatic capacity. These insights provide a mechanistic foundation for targeting CD70 as a potential therapeutic strategy in advanced ccRCC. Notably, we propose that CD70-targeted therapy may be more effective when combined with agents blocking adaptive escape pathways (e.g., Ras/ERK inhibitors), a hypothesis generated by mechanistic rescue and pharmacologic inhibition in vitro, which require further preclinical validation to confirm synergistic efficacy and clinical viability.
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Yujie Su,Yahui Hu,Yu Wang,Xiangting Xu,Yang Yuan,Yunman Li,Zeyuan Wang,Kerong Chen,Fangrong Zhang,Xuefang Ding,Min Li,Jianping Zhou,Yuan Liu,Wei Wang
Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT 1 R) and type 2 receptor (AT 2 R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT 2 (pAT 2 ) to form iRGD-PEI-MWNT-SS-CD/pAT 2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT 1 R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT 2 and efficiently inhibited angiogenesis . iRGD-PEI-MWNT-SS-CD/pAT 2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice . Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy.
研究领域:
肿瘤学
·
纳米医学
·
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）