GENE
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2022
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IF 3.913
Defeng Zhao,Gaoyu Hu,Ran Chen,Guoqiang Xiao,Shuangshuang Teng
Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa ( T. granosa ) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. In the present study, the full-length T. granosa c-Myc (Tgc-Myc) cDNA was cloned for the first time. The 3063-bp cDNA consisted of a 129-bp 5′ untranslated region (UTR), a 1746-bp 3′ UTR, and a 1188-bp open reading frame encoding a predicted protein of 395 amino acid residues. The predicted protein had a calculated molecular weight of 44.9 kDa and an estimated isoelectric point of 6.82. The predicted protein contained an N-terminal transactivation domain and a C-terminal basic helix-loop-helix leucine zipper domain, which are conserved functional domains of c-Myc proteins. Tgc-Myc showed broad tissue distribution in blood clams, with the highest expression detected in the gill and hepatopancreas. Exposure to Cd, a major heavy metal pollutant in coastal regions of the East China Sea, induced Tgc-Myc expression in gill tissues. Tgc-Myc knockdown led to reduced expression of a variety of stress response/detoxification genes in blood clams cultivated in Cd-contaminated seawater. Tgc-Myc knockdown also led to decreased expression of IGF1R , a proto-oncogene that promotes cell proliferation. These findings indicated that Tgc-Myc regulates Cd-induced stress response and detoxification in blood clams. The upregulation of Tgc-Myc may serve as an approach to generate strains with an enhanced detoxification response and consequently a low heavy metal buildup.
研究领域:
分子生物学
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环境毒理学
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海洋生物学
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PubMed
高影响因子
Molecular Therapy-Nucleic Acids
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2023
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IF 8.8
Yufei Pan,Jing Guan,Yujing Gao,Yuejie Zhu,Huantong Li,Hua Guo,Qianyi He,Zhu Guan,Zhenjun Yang
Antisense oligonucleotides (ASOs) are a class of therapeutics targeting mRNAs or genes that have attracted much attention. However, effective delivery and optimal accumulation in target tissues in vivo are still challenging issues. CT102 is an ASO that targets IGF1R mRNA and induces cell apoptosis. Herein, a detailed exploration of the tissue distribution of ASOs delivered by liposomes was carried out. A formulation that resulted in increased hepatic accumulation was identified based on multiple intermolecular interactions between DCP (cytidinyl/cationic lipid DNCA/CLD and DSPE-PEG) and oligonucleotides, including hydrogen bonding, π-π stacking, and electrostatic interactions. The structurally optimized CT102s present a novel strategy for the treatment of hepatocellular carcinoma. The gapmer CT102 MOE5 and conjugate Glu-CT102 MOE5 showed superior antiproliferation and IGF1R mRNA suppression effects at 100 nM in vitro and achieved greater efficacy at a lower dose and administration frequency in vivo . Combined transcriptome and proteome analyses revealed that additional associated targets and functional regulations might simultaneously exist in ASO therapy. These results showed that a combination of lipid encapsulation and structural optimization in the delivery of oligonucleotide drugs has favorable prospects for clinical application.
研究领域:
分子生物学
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肿瘤学
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药物递送系统
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PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2021
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IF 6.514
Haoran Xu,Yue Zhao,Xin Gao,Fang Wang,Yueqing Gu
Breast cancer is the most dangerous, among all malignant tumors that threaten women’s lives and health. Surgical resection can effectively prolong the survival time of patients with early breast cancer. Insulin-like growth factor type 1 receptor (IGF1R) is a member of the large family of receptor tyrosine kinases , and it’s significantly overexpressed in breast cancer cells, which make them ideal biomarkers for the diagnosis and surgery navigation of breast cancer. Herein, we developed a series of IGF1R-targeted probes ( YQ-L ) for fluorescent imaging in breast cancer based on the strategy of drug repositioning . YQ-L exhibited specific IGF1R binding both in vitro and in vivo, especially probe 5d exhibited higher tumor uptake with a high tumor/normal ratio in the MCF-7 tumor bearing mouse. The maximum T/N ratio of probe 5d was 4.9, which was about 3 times that of indocyanine green (ICG). Meanwhile, probe 5d displayed more favorable in vivo pharmacokinetic properties than that of ICG with less hepatic and intestinal uptake. Convenient preparation, excellent IGF1R specificity in breast cancer, rapid clearance from normal organs and good biosafety profiles of probe 5d warrant further investigations for clinical translation in detection and surgery navigation of breast cancer.
研究领域:
肿瘤学
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药学
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医学成像
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF SURGICAL RESEARCH
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2025
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IF 1.7
Jimin Cai,Jiacheng Zhang,Nan Wang,Yan Wang,Di Jia,Xin Ge
Introduction Hemorrhagic shock (HS), a life-threatening condition characterized by significant blood loss, often leads to multiple organ dysfunction, particularly renal impairment. Previous studies have demonstrated that interferon regulatory factor 1 (IRF1) deficiency exerts a protective effect against kidney function deterioration. This study aims to investigate the role of IRF1 in HS-induced renal injury and elucidate its underlying mechanisms. Materials and Methods HS model was established in male Sprague–Dawley rats by inducing shock through femoral artery bloodletting to maintain a mean arterial pressure of 40-50 mmHg for 1 h, followed by resuscitation via intravenous fluid infusion. Three days prior to HS induction, rat kidneys were injected with interfering lentivirus LV-shIRF1 (2 × 10ˆ9 TU/mL, 50 μL/d). For in vitro experiments, human monocyte-derived macrophages were generated by differentiating Tohoku Hospital Pediatrics-1 cells with 50 nM phorbol 12-myristate 13-acetate (PMA). Pyroptosis was subsequently induced by treating the differentiated macrophages with 5 μg/mL lipopolysaccharide (LPS) and 5 mM adenosine triphosphate (ATP). Results IRF1 was significantly upregulated in HS-induced rat kidneys. Histologic assays showed that IRF1 deficiency demonstrated that IRF1 deficiency alleviated kidney injury, suppressed inflammatory responses, and reduced cellular pyroptosis. Dual-luciferase reporter assays confirmed that IRF1 bound to the promoter region of insulin-like growth factor binding protein 7 (IGFBP7) and enhanced its transcriptional activity. Co-immunoprecipitation (Co-IP) and Western blot analysis further verified that IGFBP7 physically interacted with insulin like growth factor 1 receptor (IGF1R) protein. Notably, IRF1 knockdown downregulated IGFBP7 expression while concurrently increasing IGF1R phosphorylation in both in vivo and in vitro models. Functional rescue experiments revealed that IGFBP7 overexpression counteracted the suppressive effects of IRF1 deficiency on cellular pyroptosis and inflammation. Conclusions In summary, IRF1 deficiency mitigated macrophage pyroptosis and protected against HS-induced kidney injury through IGFBP7/IGF1R.
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高影响因子
Frontiers in Molecular Biosciences
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2025
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IF 4
Li Ji,Anqi Deng,Huiying Chen,Shuangyan Guo,Pingyu Wang,Ruiyi Zhang,Wenyang Chen,Taotao Fan,Lijuan Jiang,Bing Shen
Introduction BaoTaiyin (BTY) is a traditional Chinese medicine decoction. It has been used to treat recurrent miscarriage (RM). However, there are no comprehensive systematic studies to identify the chemical compositions of BTY and molecular mechanisms on RM. Finding the chemical components of BTY and clarifying the underlying processes in the treatment of RM were the goals of the study. Methods We used ultra-high-performance liquid chromatography coupled with triple quadruple time-of-flight tandem mass spectrometry to analyze the chemical components of BTY, network analysis to predict the pharmacological effects of the identified active ingredients, and cell experiments to identify potential molecular mechanisms. Results We found 12 active ingredients among 61 components identified in BTY. These identified activities were linked to regulatory effects on 127 key signaling pathways, targeting 107 proteins. Through network analysis, we determined that insulin-like growth factor 1 receptor, matrix metalloproteinases, PI3K, and STAT3 may be the core targets of BTY’s therapeutic effects on RM. We further explored this mechanism to find that aqueous extracts of BTY significantly enhanced IGFBP2 and CaMKK2 expression and trophoblast proliferation, whereas inhibitors of IGF1R/PI3K/AKT pathway or CaMKK2 blocked the effect of BTY on trophoblast proliferation. In addition, IGFBP2 siRNA suppressed BTY-induced CaMKK2 expression. Caffeic acid, as one of components of BTY, increased intracellular Ca 2+ concentration and proliferation in trophoblast. Conclusion Our research showed that BTY may have therapeutic benefits on RM through multiple targets and pathways, such as the IGF1R/PI3K/AKT and Ca 2+ /calmodulin signaling pathways.
研究领域:
中药学
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分子生物学
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生殖医学
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PubMed
高影响因子
BRAIN RESEARCH
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2025
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IF 2.6
Shan Hui,Yi Long,Lemei Zhu,Wei Shi,Qing Zheng,Lihui Liang
Background Alzheimer’s disease (AD) is characterized by cognitive decline and neuronal loss, with cellular senescence emerging as a key driver. The insulin-like growth factor-1 receptor (IGF1R) pathway is implicated in aging and AD pathology. IGF2 mRNA binding protein 2 (IGF2BP2) can stabilize IGF1R mRNA, but its role in AD-associated neuronal senescence remains unclear. Methods We established AD mouse models and H 2 O 2 -induced senescent neuronal cell models to explore the impact of IGF2BP2 in neuronal senescence and cognitive deficits. RNA pull-down assays, methylated RNA immunoprecipitation (MeRIP)-qPCR, and behavioral tests were used to elucidate the molecular mechanisms and therapeutic potential of targeting IGF2BP2. Results IGF2BP2 was significantly up-regulated in the hippocampal neurons of AD mice. This upregulation correlated with increased β-amyloid (Aβ) deposition, neuronal damage, and cognitive impairments. In vitro , IGF2BP2 knockdown in H 2 O 2 -induced senescent neurons reduced IGF1R expression and alleviated neuronal senescence, as evidenced by decreased senescence-associated secretory phenotype factors and improved cell viability. Mechanistically, IGF2BP2 stabilized IGF1R mRNA through m6A modification, enhancing its expression. Knockdown of IGF2BP2 decreased IGF1R mRNA stability and expression, thereby mitigating neuronal senescence. In AD mice, IGF2BP2 knockdown improved cognitive function, reduced Aβ deposition, and delayed neuronal senescence. Conclusion IGF2BP2 contributes to neuronal senescence and cognitive deficits in AD by regulating IGF1R expression through m6A modification.
研究领域:
神经科学
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分子生物学
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表观遗传学
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衰老研究
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神经退行性疾病
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PubMed
高影响因子
Journal of Translational Medicine
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2023
·Vol. 21
·期 1
·1-14
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IF 7.4
Chen Shengnan,Li Bo,Chen Lei,Jiang Hongli
Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.Conclusion sRES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
研究领域:
药理学
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分子生物学
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糖尿病
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肾病学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2026
·Vol. 27
·期 5
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IF 5.6
Tong Chen,Jing Zhang,Shaoqin Jian,Bocen Chen,Yingjie Ma,Wenguang Wang,Tianpeng Ma,Jiran Shi,Jin Yang,Man Xiao
Paederia scandens(Lour.)Merris a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects ofpaederoside(PSG) have not been thoroughly investigated; therefore, in this study,Caenorhabditis elegans(C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan ofC. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant geneskn-1and longevity-associated genedaf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited inC. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component ofPaederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feedingC. elegansPSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.
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高影响因子
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