期刊:
Mini-Reviews in Medicinal Chemistry,2024年 ISSN:1389-5575
作者机构:
[Peng, Junmei Peng; Lei, Xiaoyong; Huang, Honglin; Yang, Jun; Zhang, Yuan; Wu, Xin; Sun, Xueyan; Tang, Guotao; Liu, Chang] Department of Pharmacy, School of Pharmacy, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China
摘要:
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease. According to the American Cancer Society's 2021 cancer data report, new cases of CML account for about 15% of all leukemias. CML is generally divided into three stages: chronic phase, accelerated phase, and blast phase. Nearly 90% of patients are diagnosed as a chronic phase. Allogeneic stem cell transplantation and chemotherapeutic drugs, such as interferon IFN-α were used as the earliest treatments for CML. However, they could generate obvious side effects, and scientists had to seek new treatments for CML. A new era of targeted therapy for CML began with the introduction of imatinib, the first-generation BCR-ABL kinase inhibitor. However, the ensuing drug resistance and mutant strains led by T315I limited the further use of imatinib. With the continuous advancement of research, tyrosine kinase inhibitors (TKI) and BCR-ABL protein degraders with novel structures and therapeutic mechanisms have been discovered. From biological macromolecules to classical target protein inhibitors, a growing number of compounds are being developed to treat chronic myelogenous leukemia. In this review, we focus on summarizing the current situation of a series of candidate small-molecule drugs in CML therapy, including TKIs and BCR-ABL protein degrader. The examples provided herein describe the pharmacology activity of small-molecule drugs. These drugs will provide new enlightenment for future treatment directions.
期刊:
Mini-Reviews in Medicinal Chemistry,2024年 ISSN:1389-5575
作者机构:
[Chen, Ke-Qian; Wang, Shu-Zhi; Wang, Zong-Bao; Zhang, Yu-Qing] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China;[Chen, Ke-Qian; Wang, Shu-Zhi; Wang, Zong-Bao; Zhang, Yu-Qing] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China
摘要:
Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson's disease, ischemic heart disease, myocardial ischemia-reperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.
作者机构:
[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Zhao, Jun; Fan, Shifan; Song, Chao] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Zhang, Qinyi; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Zhang, Yuexin; Li, Chunquan; Zhao, Yu; Huang, Xuemei; Xie, Liyuan; Zhang, Guorui; Fan, Shifan; Song, Chao] Univ South China, Affiliated Hosp 1, Cardiovasc Lab Big Data & Imaging ArtificialIntell, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent,Natl Hlth Commi, Hengyang 421001, Hunan, Peoples R China.
摘要:
Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237 051 cell type-specific GRNs (62 999 692 TF-target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF-target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizing and downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions. Graphical Abstract
作者机构:
[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhu, Hongxia] Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China;[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhu, Hongxia] School of Pharmacy, Hengyang Medical College, University of South China, Hengyang, Hunan, China;[Zhang, Taolan] Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China;[Hu, Hongjuan] Department of Public Health Service, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China;[Jiang, Lingxiang] Department of Radiation Oncology, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA
通讯机构:
[Zou, Mingxiang; Feng, Yaoguang] D;[Zhou, Junlin] T;Department of Cardiothoracic Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. Electronic address:;The First Affiliated Hospital, Health Management Center, Hengyang Medical School, University of South China, Hengyang 421001, China. Electronic address:;Department of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. Electronic address:
摘要:
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and recent studies have found that CRC patients are at increased risk for cardiovascular disease (CVD). This study aimed to investigate competing causes of death and prognostic factors among a large cohort of CRC patients and to describe cardiovascular-specific mortality in relation to the US standard population. METHODS: This registry-based cohort study identified patients diagnosed with CRC between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database in the US. Cumulative mortality functions, conditional standardized mortality ratios, and cause-specific hazard ratios were calculated. RESULTS: Of the 563,298 eligible CRC patients included in this study, 407,545 died during the follow-up period. CRC was the leading cause of death, accounting for 49.8% of all possible competing causes of death. CVD was the most common non-cancer cause of death, accounting for 17.8% of total mortality. This study found that CRC patients have a significantly increased risk of cardiovascular-specific mortality compared to the US standard population, with the risk increasing with age and extended survival time. CONCLUSION: This study highlights the need to develop multidisciplinary prevention and management strategies for CRC and CVD to improve CRC patients' survival and quality of life.
期刊:
Naunyn-Schmiedeberg's Archives of Pharmacology,2024年 ISSN:0028-1298
通讯作者:
Xiao, Junhui;Li, R
作者机构:
[Shen, Lixian; Tang, Lijing; Li, Rong; Li, R; Xiao, Junhui; Wang, Mei; Xiao, JH; Liu, Meng] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Wang, Mei; Liu, Meng] Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.
通讯机构:
[Li, R ; Xiao, JH] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.
关键词:
Doxorubicin;Ferroptosis;Liquiritin;Solute carrier family 7 member;Glutathione peroxidase 4
摘要:
Solute carrier family 7 member (SLC7A11) and glutathione peroxidase 4 (GPX4) mediated ferroptosis in doxorubicin-induced cardiotoxicity. Based on the bioinformatics analysis, liquiritin, a flavonoid isolated from the rhizome part of Glycyrrhiza glabra with activities of anti-inflammatory and anti-oxidant, is forecasted to synchronously with ferroptosis-relevant protein. This study aims to investigate the effect of liquiritin on doxorubicin-induced cardiotoxicity and the underlying mechanisms. The C57BL/6 J mice heart or cardiomyocytes were subjected to doxorubicin in vivo or in vitro, which were treated with liquiritin at different dosages. The heart or H9c2 cell cardiotoxicity, relevant protein levels, and ferroptosis were measured by methods of biochemistry, flow cytometry, or Western blot. The mice treated with doxorubicin showed evident cardiotoxicity, concomitant with the downregulation of SLC7A11 and GPX4, and accelerate ferroptosis. Administration of liquiritin could relieve the heart injury, accompanied by restoration of the levels of SLC7A11 and GPX4, and inhibit ferroptosis. And liquiritin ameliorated similar effects in doxorubicin-treated H9c2 cells. Based on these findings, we conclude that liquiritin can protect the doxorubicin-induce mice's cardiotoxicity, and its beneficial effect is related to the reduction of ferroptosis through a mechanism involving the regulation of the SLC7A11/GPX4 pathway.
作者机构:
[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Mu, Xinxin; Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Song, Chao; Tang, Huifang; Yin, Mingxue; Zhang, Hang] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qinyi; Li, Chunquan; Song, Shuang; Zhang, Guorui; Yin, Mingxue] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要:
Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs. Graphical Abstract
摘要:
Endothelial cell apoptosis driven by inflammation (TNF-alpha) plays a critical role in the pathogenesis of atherosclerosis, but the exact molecular mechanisms are not clearly elucidated. MicroRNA (miR)-29 families (a/b/c) take important roles in pathophysiological processes of atherosclerosis, also the underlying mechanisms have not been fully clarified. The aims are to explore whether or not miR-29 families mediate the apoptotic effects of TNF-alpha on endothelial cells and uncover the underlying molecular mechanisms. In this study, MTT assay and flow cytometer analysis were employed respectively to determine the proliferation and apoptosis of human umbilical vascular endothelial cells (HUVECs) under TNF-alpha exposure. Real-time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF-alpha could inhibit HUVEC proliferation and induce HUVEC apoptosis in a positive dose-and time-dependent manner, with a similar way of miR-29a upregulation, but no effects on miR-29b/c. Upregulation of miR-29a with its mimics enhanced the apoptotic effect of TNF-alpha on HUVECs, but downregulation of miR-29a using anti-miR-29a blocked up its apoptotic effect. MiR-29a inhibited the expression of PI3Kp85 alpha and Bcl-2 and blocked up the signal transduction of PI3K/AKT/Bcl-2 axis to mediate the apoptotic effect of TNF-alpha on HUVECs. Mediating the inflammation-driven endothelial cell apoptosis is an important biology mechanism by which miR-29a promotes atherosclerosis and its complications. MiR-29a will be a potential diagnostic and therapeutic target for atherosclerotic cardiovascular diseases; it is worthwhile to further study.
期刊:
Journal of Hazardous Materials,2024年464:132986 ISSN:0304-3894
通讯作者:
Wang, Jikai
作者机构:
[Zhu, Yanli] School of Resources and Environment, Hunan University of Technology and Business, Changsha 410205, Hunan, PR China;[Wang, Jikai] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China. Electronic address: jkwang@hnu.edu.cn;[Xie, Zhulan; Sun, Yiyang; Zeng, Pengfei] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China;[Chen, Danjun; Fu, Chengxiao] The First Affiliated Hospital, Department of Pharmacy, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, 421001 Hunan, PR China;[Jiang, Yuehua] Department for Animal Husbandry & Aquaculture Products Quality Control, Hengyang Animal Husbandry and Aquaculture Affairs Center, Hengyang 421001, Hunan, PR China
通讯机构:
[Wang, Jikai] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China. Electronic address:
关键词:
Desorption ionization mechanism;Environmental analysis;MALDI-MS;Nano-matrix;Two-dimensional material
摘要:
Laser desorption ionization mass spectrometry (LDI-MS) aroused intensive concerns for the merits of label-free and high-throughput analysis. Here, we designed a silver nanoparticles (AgNP)-modified indium vanadate nanosheets with doping samarium (AgNP@InVO(4):Sm) nanosheets. The developed AgNP@InVO(4):Sm nanosheets (AIVON) were synthesized based on the microemulsion-mediated solvothermal method and ultraviolet-assisted in situ formation of AgNP, then for the first time applied as a matrix in LDI-MS analysis. With the advantages including enhanced MS signal, little matrix-related background, high reproducibility, and good salt tolerance, AIVON exhibited much better prospect than non-modified indium vanadate nanosheets with doping samarium (IVON) and traditional organic matrix, thus allowing sensitive MS detection for a wide range of low-molecular-weight (LMW) molecules. Moreover, by coupling with headspace sampling thin-film microextraction (TFME), a kind of representative pollutant chlorophenols were identified and quantified via AIVON-assisted LDI-MS in environmental and biological samples. Volatile LMW pollutants could be preconcentrated after TFME, hence a sensitive and rapid assay with negligible sample matrix effect was realized by using AIVON-assisted LDI-MS. It is anticipated that this novel nano-matrix AIVON and the proposed TFME coupling detection strategy were of competitive merits for LDI-MS analysis in the fields of environment, biomedicine, and agriculture.
期刊:
Molecular and Cellular Biochemistry,2023年 ISSN:0300-8177
通讯作者:
Jiang, Zhisheng
作者机构:
[He, Shuya; He, Siqi; Jiang, Zhisheng; Ma, Yun; Gu, Tianhe] Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Zhisheng; Ma, Yun] Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Hunan, Peoples R China.;[Ma, Yun] Univ South China, Hengyang Med Sch, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Jiang, Zhisheng] I;Institute of Biochemistry and Molecular Biology, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, China.;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, 421001, Hunan, China.
摘要:
Cardiovascular disease (CVD) has a high incidence and low cure rate worldwide, and atherosclerosis (AS) is the main factor inducing cardiovascular disease, of which lipid deposition in the vessel wall is the main marker of AS. Currently, although statins can be used to lower lipids and low-density lipoprotein (LDL) in AS, the cure rate for AS remains low. Therefore, there is an urgent need to develop new therapeutic approaches, and stem cells are now widely studied, while stem cells are a class of cell types that always maintain the ability to differentiate and can differentiate to form other cells and tissues, and stem cell transplantation techniques have shown efficacy in the treatment of other diseases. With the establishment of cellular therapies and continued research in stem cell technology, stem cells are also being used to address the problem of AS. In this paper, we focus on recent research advances in stem cell therapy for AS and briefly summarize the relevant factors that induce the formation of AS. We mainly discuss the efficacy and application prospects of mesenchymal stem cells (MSCs) for the treatment of AS, in addition to the partial role and potential of exosomes in the treatment of AS. Further, provide new ideas for the clinical application of stem cells.
期刊:
Combinatorial Chemistry & High Throughput Screening,2023年 ISSN:1386-2073
作者机构:
[Xiang, Yijun; Yang, Zehua; Wang, Yanjie; Mi, Pengbing; Yao, Xu; Ai, Wenbin; Li, Jiaxin; Li, Xiaoshun; Zheng, Zitong; Jiang, Jingyi] Department of Pharmacy, Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
摘要:
Resveratrol is one of the most interesting naturally-occurring nonflavonoid phenolic compounds with various biological activities, such as anticancer, neuroprotection, antibacterial, and anti-inflammatory. However, there is no clinical usage of resveratrol due to either its poor activity or poor pharmacokinetic properties. Heteroarenes-modified resveratrol is one pathway to improve its biological activities and bioavailability, and form more modification sites. In this review, we present the progress of heteroaryl analogues of resveratrol with promising biological activities in the latest five years, ranging from the synthesis to the structure-activity relationship and mechanism of actions. Finally, introducing heteroarenes into resveratrol is an effective strategy, which focuses on the selectivity of structure-activity relationship in vivo.
关键词:
Anti-breast cancer activities;Baker-Venkataraman reaction;Fluorinated-genistein derivatives;Genistein;MTT assay;structure-activity relationship
摘要:
Background: Genistein has been limited in clinical application due to its low bioavailability, extremely poor liposolubility, and fast glycosylation rate, though it possesses anti-breast cancer activity. Therefore, the discovery of novel genistein derivatives is an urgency.<&wdkj&>Objective: To enhance the anti-breast cancer activity of genistein, a series of novel fluorinated genistein derivatives were synthesized.<&wdkj&>Methods: Their in vitro antitumor activity was investigated by the MTT assay against three cancer cell lines, via, MDA-MB-231, MCF-7, and MDA-MB-435, respectively.<&wdkj&>Results: Analogs 1d, 2b, and 3b showed remarkable anticancer activities compared to tamoxifen, a clinical anti-breast cancer drug on the market.<&wdkj&>Conclusion: The activities against breast cancer of genistein were enhanced by introducing the 7- alkoxyl group and fluorine atom into the B-ring. Therefore, these compounds may be potential candidates for treating breast cancer.
摘要:
HYPOTHESIS: Construction of dual gatekeepers-functionalized mesoporous organic silica nanoparticles (MONs) with both physical and chemical mechanisms for modulated drug delivery properties provides one solution to the extracellular stability vs. intracellular high therapeutic efficiency of MONs that hold great potential for clinical translations. EXPERIMENTS: We reported herein facile construction of diselenium-bridged MONs decorated with dual gatekeepers, i.e., azobenzene (Azo)/polydopamine (PDA) for both physical and chemical modulated drug delivery properties. Specifically, Azo can act as a physical barrier to block DOX in the mesoporous structure of MONs for extracellular safe encapsulation. The PDA outer corona serves not only as a chemical barrier with acidic pH-modulated permeability for double insurance of minimized DOX leakage in the extracellular blood circulation but also for inducing a PTT effect for synergistic PTT and chemotherapy of breast cancer. FINDINGS: An optimized formulation, DOX@(MONs-Azo3)@PDA resulted in approximately 1.5 and 2.4 fold lower IC50 values than DOX@(MONs-Azo3) and (MONs-Azo3)@PDA controls in MCF-7 cells, respectively, and further mediated complete tumor eradication in 4T1 tumor-bearing BALB/c mice with insignificant systematic toxicity due to the synergistic PTT and chemotherapy with enhanced therapeutic efficiency.
作者机构:
[Zhou, Jing; Yao, Xu; Xiang, Yi-Jun; Liu, Shun] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Peoples R China.;[Lin, Jin-Hong; Xiao, Ji-Chang; Xiang, Yi-Jun] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.;[Lin, Jin-Hong] Shanghai Univ, Innovat Drug Res Ctr, Dept Chem, Shanghai 200444, Peoples R China.
通讯机构:
[Jin-Hong Lin; Ji-Chang Xiao] K;[Xu Yao] I;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 421001 Hengyang, PR China<&wdkj&>Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, 200032 Shanghai, PR China<&wdkj&>Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, 200032 Shanghai, PR China<&wdkj&>Department of Chemistry, Innovative Drug Research Center, Shanghai University, 200444 Shanghai, PR China
摘要:
Described here is the R3P/ICH2CH2I-promoted dehydroxylative sulfonylation of alcohols with a variety of sulfinates. In contrast to previous dehydroxylative sulfonylation methods, which are usually limited to active alcohols, such as benzyl, allyl, and propargyl alcohols, our protocol can be extended to both active and inactive alcohols (alkyl alcohols). Various sulfonyl groups can be incorporated, such as CF3SO2 and HCF2SO2, which are fluorinated groups of interest in pharmaceutical chemistry and the installation of which has received increasing attention. Notably, all reagents are cheap and widely available, and moderate to high yields were obtained within 15 min of reaction time.
作者机构:
[Fu, Yuting; Jiang, Binyuan; Yuan, Yeqin] Univ South China, Affiliated Changsha Cent Hosp, Med Res Ctr, Hengyang Med Sch, Changsha 410004, Peoples R China.;[Zhou, Ziwei; Long, Huizhi] Univ South China, Sch Pharm, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Jiang, Binyuan] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Peoples R China.
通讯机构:
[Binyuan Jiang] M;Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China<&wdkj&>Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China
关键词:
breast cancer;clinical trial drugs;natural products;PI3K–AKT pathway
摘要:
Abstract: Breast cancer is the most commonly diagnosed cancer in women. The high incidence of breast cancer, which is continuing to rise, makes treatment a significant challenge. The PI3K–AKT pathway and its downstream targets influence various cellular processes. In recent years, mounting evidence has shown that natural products and synthetic drugs targeting PI3K–AKT signaling have the potential to treat breast cancer. In this review, we discuss the role of the PI3K–AKT signaling pathway in the occurrence and development of breast cancer and highlight PI3K–AKT-targeting natural products and drugs in clinical trials for the treatment of breast cancer. Keywords: PI3K–AKT pathway; breast cancer; natural products; clinical trial drugs
期刊:
Clinical and Experimental Medicine,2023年 ISSN:1591-8890
通讯作者:
Zhang, TL
作者机构:
[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, Hongxia; Zhang, Jingdi; Wang, Siyu] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, Hongxia; Zhang, Jingdi; Wang, Siyu] Univ South China, Hengyang Med Coll, Sch Pharm, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Taolan; Zhang, TL] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Phase Clin Trial Ctr 1, Hengyang 421001, Hunan, Peoples R China.;[Yan, Ting] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Lingxiang] Indiana Univ Sch Med, Melvin & Bren Simon Comprehens Canc Ctr, Dept Radiat Oncol, Indianapolis, IN 46202 USA.
通讯机构:
[Zhang, TL ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Pharm, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Phase Clin Trial Ctr 1, Hengyang 421001, Hunan, Peoples R China.
关键词:
Breast cancer;Immune checkpoint-related genes;Immune infiltration;Immunotherapy
摘要:
Breast cancer is one of the most prevailing forms of cancer globally. Immunotherapy has demonstrated efficacy in improving the overall survival of breast cancer. The aim of us was to formulate a novel signature predicated on immune checkpoint-related genes (ICGs) that could anticipate the prognosis and further analyze the immune status of patients with breast cancer. After acquiring data, we pinpointed the definitive ICGs for constructing the prognostic model of breast cancer. We constructed a novel prognostic model and created a fresh risk score called Immune Checkpoint-related Risk Score in breast cancer (ICRSBC). The nomogram was constructed to evaluate the accuracy of the model, and the new web-based tool was created to be more intuitive for predicting prognosis. We also investigated immunotherapy responsiveness and analyzed the tumor mutational burden (TMB) in ICRSBC subgroups. The ICRSBC was found to have significant correlations with the immune environment, immunotherapy responsiveness, and TMB. The expression levels of the 9 ICGs that construct the prognostic model and their promoter methylation levels are significantly different between breast cancer and normal tissues. Furthermore, the mutation profiles, the copy number alterations, and the levels of protein expression also exhibit marked disparities among the 9 ICGs. We have identified and validated a novel signature related to ICGs that is strongly associated with breast cancer progression. This signature enables us to create a risk score for prognosticating the survival and assessing the immune status of individuals affected by breast cancer.
摘要:
Research on porphyrin-based photosensitizing drugs is becoming increasingly popular. They possess unique diagnostic capabilities and therapeutic effects that have gained wide recognition in oncology drug development. In recent years, the rapid growth of nanotechnology has brought great hope for nanopharmaceutical formula-tions. By combining porphyrins with various nanomaterials, people have improved the properties of porphyrin compounds, making drug delivery easier. Porphyrin-based nanoparticles can enhance the effect of photodynamic therapy for cancer treatment, providing opportunities for achieving complex targeting strategies and versatility with promising applications in drug carriers, tumor imaging, and treatment. This paper reviews recent porphyrin nanodrugs, including inorganic-organic hybrid nanoparticles, nanomicelles, self-assembled nanoparticles, and combination therapeutic nanodrugs, and their actions and effects on cancer cells when performing photodynamic therapy. It also discusses the drawbacks as well as the prospects for development.
期刊:
Journal of Pharmacy and Pharmacology,2023年75(3):363-369 ISSN:0022-3573
通讯作者:
Shu-zhi Wang
作者机构:
[Liu, Shu-ting; Wang, Shu-zhi; Wang, Zong-bao; Chen, Ming-xin; Deng, Bo-yan] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Liu, Shu-ting; Wang, Shu-zhi; Wang, Zong-bao; Chen, Ming-xin; Deng, Bo-yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
通讯机构:
[Shu-zhi Wang] I;Institute of Pharmacy and Pharmacology, University of South China , Hengyang , China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China , Hengyang , China
摘要:
Salusins are discovered in 2003 and divided into salusin-α and salusin-β, which are bioactive peptides with hemodynamic and mitotic activity and mainly distributed in plasma, urine, endocrine glands and kidneys. A large number of studies have shown that salusins can regulate lipid metabolism, inflammatory response and vascular proliferation. Despite the profound and diverse physiological properties of salusins, the exact mechanism of their cardiovascular effects remains to be determined. The potential mechanisms of action of salusins in cardiovascular-related diseases such as atherosclerosis, hypertension, heart failure, myocardial infarction and myocarditis, and their use as biomarkers of cardiovascular disease are discussed. This review aims to provide a new strategy for the diagnosis and prevention of clinical cardiovascular diseases.
作者机构:
[Lv, Yun-Cheng; Tang, Yan-Yan; Xie, Wei; Li, Yuan; Lan, Gan; Zhang, Min; Zhang, Chi; Shi, Jin-Feng; Yin, Wei-Dong; Tang, Chao-Ke] Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China;Yongzhou Vocational and Technical College, Yongzhou, Hunan, 425000, China;School of Nursing, University of South China, Hengyang, Hunan, 421001, China;[Liu, Xiang-Yu] Department of Biochemistry and Molecular Biology, School of Life Sciences and Technology, University of South, Hengyang, Hunan, 421001, China;[Zheng, Xi-Long] Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada
摘要:
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs.6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig.6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig.2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.