作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hengyang Med Sch, Canc Res Inst, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Res Inst, Hengyang, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Cancer Research Institute, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
作者机构：
[Zhang, Taolan; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, HongXia] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421000, Hunan, Peoples R China.;[Zhang, Taolan; Yang, Xiaoyan; Hu, Haihong; Zhan, Wendi; Li, Zhicheng; Zhang, TL; Wang, Hanbin; Zhu, HongXia] 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, Affiliated Hosp 1, Hengyang Med Sch, Chinese Tradit Med CTM Res Platform Major Epidem T, Hengyang 421000, Hunan, Peoples R China.
通讯机构：
[Zhang, TL ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421000, 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, Affiliated Hosp 1, Hengyang Med Sch, Chinese Tradit Med CTM Res Platform Major Epidem T, Hengyang 421000, Hunan, Peoples R China.
摘要：
Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancerand PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases.
期刊：
Drug Development Research,2023年84(3):406-422 ISSN：0272-4391
通讯作者：
Tang, G.;Wang, Z.
作者机构：
[Xie, Zhizhong; Zhao, Yin; Lei, Xiaoyong; Sun, Xueyan; Zhao, Jingduo; Tang, Guotao] Heng Yang Med Sch, Inst Pharm & Pharmacol, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang, Hunan, Peoples R China.;[Li, Yong; Liu, Xingyun] Univ South China, Nanhua Hosp, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Huang, Sheng] Jiuzhitang Co Ltd, Changsha, Hunan, Peoples R China.;[Wang, Zhe] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang, Hunan, Peoples R China.;[Wang, Zhe] Univ South China, Affiliated Hosp 2, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhe Wang] T;[Guotao Tang] I;The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hunan, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, HengYang Medicial School, Hengyang, Hunan, China
摘要：
Treatment of Klebsiella pneumoniae causing pyogenic infections is challenging. The clinical and molecular characteristics of Klebsiella pneumoniae causing pyogenic infections are poorly understood, and antibacterial treatment strategies are limited. We analyzed the clinical and molecular characteristics of K. pneumoniae from patients with pyogenic infections and used time-kill assays to reveal the bactericidal kinetics of antimicrobial agents against hypervirulent K. pneumoniae (hvKp). A total of 54 K. pneumoniae isolates were included, comprising 33 hvKp and 21 classic K. pneumoniae (cKp) isolates, and the hvKp and cKp isolates were identified using five genes (iroB, iucA, rmpA, rmpA2, and peg-344) that have been applied as hvKp strain markers. The median age of all cases was 54 years (25th and 75th percentiles, 50.5 to 70), 62.96% of individuals had diabetes, and 22.22% of isolates were sourced from individuals without underlying disease. The ratios of white blood cells/procalcitonin and C-reactive protein/procalcitonin were potential clinical markers for the identification of suppurative infection caused by hvKp and cKp. The 54 K. pneumoniae isolates were classified into 8 sequence type 11 (ST11) and 46 non-ST11 strains. ST11 strains carrying multiple drug resistance genes have a multidrug resistance phenotype, while non-ST11 strains carrying only intrinsic resistance genes are generally susceptible to antibiotics. Bactericidal kinetics revealed that hvKp isolates were not easily killed by antimicrobials at susceptible breakpoint concentrations compared with cKp. Given the varied clinical and molecular features and the catastrophic pathogenicity of K. pneumoniae, it is critical to determine the characteristics of such isolates for optimal management and effective treatment of K. pneumoniae causing pyogenic infections.IMPORTANCE Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited. We analyzed the clinical and molecular features of 54 isolates from patients with various pyogenic infections. We found that most patients with pyogenic infections had underlying diseases, such as diabetes. The ratio of white blood cells to procalcitonin and the ratio of C-reactive protein to procalcitonin were potential clinical markers for differentiating hypervirulent K. pneumoniae strains from classical K. pneumoniae strains that cause pyogenic infections. K. pneumoniae isolates of ST11 were generally more resistant to antibiotics than non-ST11 isolates. Most importantly, hypervirulent K. pneumoniae strains were more tolerant to antibiotics than classic K. pneumoniae isolates. Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited.
期刊：
CURRENT MOLECULAR MEDICINE,2023年23(7):668-677 ISSN：1566-5240
通讯作者：
Long, Shuanglian;Mo, Zhongcheng;He, WG
作者机构：
[Luo, Min; Liu, Jiang; He, Weiguo; Mo, Zhongcheng; Gui, Zihao; Long, Shuanglian] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Li, Tangluo] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Peng, Mindan; Liu, Jiang] Univ South China, Hunan Prov Innovat Training Base Med Postgrad, Yueyang 416000, Hunan, Peoples R China.;[Peng, Mindan; Liu, Jiang] Yueyang Women & Childrens Med Ctr, Yueyang 416000, Hunan, Peoples R China.;[Mo, Zhongcheng] Guilin Med Univ, Guangxi Key Lab Diabet Syst Med, Guilin 541000, Guangxi, Peoples R China.
通讯机构：
[He, WG ; Mo, ZC; Long, SL] U;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.
关键词：
CPP;Central precocious puberty;GnRH.;MKRN3;Makorin RING finger protein 3;Puberty initiation
摘要：
Puberty is initiated from the continuous and growing pulsatile secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus and then the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Numerous factors involve pubertal initiation, whose abnormality may come from the dysfunction of these regulators. Makorin RING finger protein 3 (MKRN3) inhibits the secretion of GnRH and plays indispensable roles during the development of pubertal onset, and mutations of MKRN3 showed the commonest genetic cause of central precocious puberty (CPP). Recently, growing studies have revealed the functional mechanisms of MKRN3 in the pubertal initiation and the occurrence of CPP. In this review, we mainly summarized the research advances on the roles of MKRN3 in the development of pubertal onset and their underpinning mechanisms, contributing to a better understanding of the precise mechanisms of pubertal initiation and the pathogenesis of CPP.
关键词：
Breast cancer;Lead compounds;Multidrug resistance
摘要：
Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.
作者机构：
[Zhang, Jing; Xie, Zhizhong; Lei, Xiaoyong; Ouyang, Chenglin; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang Medicial Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhe] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Li, Yong; Liu, Xingyun] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Huang, Sheng] Jiuzhitang Co Ltd, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Zhe Wang] T;[Guotao Tang] I;The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medicial School, University of South China, Hengyang, Hunan 421001, China
摘要：
Generally, hypoxia-inducible factor-1 alpha (HIF-1 alpha) is highly expressed in solid tumors, it plays a key role in the occurrence and development of tumors, hindering cancer treatment in various ways. The antitumor activity and pharmacological mechanism of YC-1 [3-(5 '-hydroxymethyl-2 '-furyl)-1-benzyl indazole], an HIF-1 alpha inhibitor, and the design and synthesis of its derivatives have attracted tremendous attention in the field of antitumor research. YC-1 is a potential drug candidate and a lead compound for tumor therapy. Hence, the multifaceted mechanism of action of YC-1 and the structure activity relationship (SAR) of its derivatives are important factors to be considered for the development of HIF-1 alpha inhibitors. Therefore, this review aimed to provide a comprehensive overview of the various antitumor mechanisms of YC-1 in antitumor research and an in-depth summary of the SAR for the development of its derivatives. A full understanding and discussion of these aspects are expected to provide potential ideas for developing novel HIF-1 alpha inhibitors and antitumor drugs belonging to the YC-1 class. The review also highlighted the application prospects of the YC-1 class of potential antitumor candidates, and provided some unique insights about these antitumor agents.
期刊：
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY,2023年26(9):e202200727- ISSN：1434-1948
通讯作者：
Dr. Pengbing Mi<&wdkj&>Prof. Dr. Ying-Wu Lin<&wdkj&>Dr. Pengbing Mi Dr. Pengbing Mi Dr. Pengbing Mi<&wdkj&>Prof. Dr. Ying-Wu Lin Prof. Dr. Ying-Wu Lin Prof. Dr. Ying-Wu Lin
作者机构：
[Lang, Jia-Jia; Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Mi, Pengbing] Univ South China, Dept Pharm, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Gao, Shu-Qin; Lin, Ying-Wu; Wang, Xiao-Juan] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.;[Tan, Xiangshi] Fudan Univ, Dept Chem & Inst Biomed Sci, Shanghai 200433, Peoples R China.
通讯机构：
[Dr. Pengbing Mi; Dr. Pengbing Mi Dr. Pengbing Mi Dr. Pengbing Mi] D;[Prof. Dr. Ying-Wu Lin; Prof. Dr. Ying-Wu Lin Prof. Dr. Ying-Wu Lin Prof. Dr. Ying-Wu Lin] H;Hengyang Medical College School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001 P. R. China<&wdkj&>Key Lab of Protein Structure and Function of Universities in Hunan Province, University of South China, Hengyang, 421001 P. R. China<&wdkj&>Department of Pharmacy Hengyang Medicinal School, University of South China, Hengyang, Hunan, 421001 P. R. China
关键词：
enzymes;model complex;molybdenum;oxygen atom transfer;nitrate reduction;S, N-bidentate ligands
摘要：
Two new Mo‐complexes with N, S‐bidentate ligands were synthesized, and show good catalytic activity in the reduction of nitrate to nitrite. The addition of Lewis acid Sc(III) significantly accelerated the cycle rate of the Mo‐catalyst. Abstract Two readily‐accessible molybdenum complexes with low sterically hindered S, N‐bidentate ligands were designed for the reduction of nitrate to nitrite. The Lewis acid Sc(III) acted as a significant co‐catalyst to enhance the catalytic efficiency by activating the N−O bond of nitrate. This study indicates that molybdenum complexes in cooperation with a Lewis acid offer functional Mo‐catalyst systems, which present functional artificial models of the natural molybdenum enzymes.
摘要：
Impaired endothelium-dependent vasodilation in atherosclerosis is a high-risk factor for myocardial infarction and ischemic stroke, and inflammation, necroptosis and apoptosis contribute to endothelial dysfunction in atherosclerosis. Although DL-3-n-butylphthalide (NBP) has been widely used in treating ischemic stroke, its effect on endothelium-dependent vasodilation remains unknown. This study aims to explore whether NBP is able to improve endothelium-dependent vasodilation in atherosclerosis and the underlying mechanisms. Male ApoE(-/-) mice were fed with a high-fat diet (HFD) for 9-16 weeks to establish a model of atherosclerosis. NBP were given to the mice after eating HFD for 6 weeks and atorvastatin served as a positive control. The endothelium-dependent vasodilation, the blood flow velocity, the atherosclerotic lesion area, the serum levels of lipids, inflammatory cytokines and necroptosis-relevant proteins (RIPK1, RIPK3 and MLKL), and the endothelial necroptosis and apoptosis within the aorta were measured. Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL) for 48h to mimic endothelial injury in atherosclerosis, lactate dehydrogenase release, the ratio of necroptosis and apoptosis and the expression of necroptosis-relevant proteins were examined. Similar to atorvastatin, NBP improves endothelium-dependent vasodilation, decreases aortic flow velocity and reduces atherosclerotic lesion area in HFD-fed ApoE(-/-) mice, concomitant with a reduction in serum lipids, inflammatory cytokines and necroptosis-relevant proteins, and endothelial necroptosis and apoptosis. Consistently, NBP inhibited necroptosis and apoptosis in ox-LDL-treated HUVECs. Based on these observations, we conclude that NBP exerts beneficial effects on improving the endothelium-dependent vasodilation in atherosclerosis via suppressing inflammation, endothelial necroptosis and apoptosis.
作者机构：
[Liu, Qian; Yang, Xuefeng; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang 421002, Hunan, Peoples R China.;[Yuan, Lin; Yuan, Jie; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.;[Yuan, Jie] Henan Normal Univ, Sch Chem & Chem Engn, Henan Key Lab Green Chem Media & React, Key Lab Green Chem Media & React,Minist Educ, Xinxiang 453007, Peoples R China.;[He, Longwei; Jiang, Renfeng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Hunan, Peoples R China.
通讯机构：
[Lin Yuan] S;[Dan Cheng] H;State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China<&wdkj&>Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
摘要：
γ-Glutamyltransferase (GGT) has been recognized as an important clinical biomarker that is closely related to many diseases. Visualizing the GGT fluctuation facilitates early disease-related diagnosis and therapy. Herein, an activated probe (NIR-GGT) for the imaging of GGT activity was prepared. The probe consists of a stable NIR fluorophore with the tunable amino group decorated with the γ-glutamate group as a GGT-sensing unit linked by a self-elimination group. NIR-GGT can sensitively recognize GGT and cause a strong turn-on fluorescent and photoacoustic signal. The up-regulation of the GGT expression in acetaminophen-induced acute liver injury was imaged using NIR-GGT. The probe can track changes in the GGT level in the early stages of drug-induced acute liver injury (DIALI) and its remedy process by fluorescent and photoacoustic dual-modality imaging with a high temporal-spatial resolution. NIR-GGT can also be used to differentiate between tumor and para-carcinowa tissues in vivo. The probe may be a potential tool for the diagnosis of early-stage DIALI and accurate tumor resection in the clinical field.
摘要：
With the continuous cognition of the relationship between tumor cells and tumor immune microenvironment, immunotherapy based on the immune checkpoint blockade has achieved great breakthroughs, led to improved clinical outcomes, and prolonged survival for cancer patients in recent years. Nevertheless, the de novo or acquired resistance to immunotherapy has greatly counteracted the efficacy, leading to a 20%-40% overall response rate. Thus, further in-depth understanding of the regulation of the tumor microenvironment and antitumor immunity is urgently warranted. Ubiquitination-mediated protein degradation plays vital roles in protein stabilization, activation, and dynamics as well as in cellular homeostasis modulation. The dysregulated ubiquitination and deubiquitination are closely related to the changes in physiological and pathological processes, which subsequently result in a variety of diseases including cancer. In this review, the authors first summarize the current knowledge about the involvement of the ubiquitin-proteasome system in tumor development with the ubiquitin conjugation-regulated stability of p53, phosphatase and tensin homolog, and Myc protein as examples, then dissect the potential implications of ubiquitination-mediated immune checkpoints degradation in tumor microenvironment and immune responses, and finally discuss the effects of therapeutically targeting the ubiquitin-proteasome pathway on immunotherapy, with the goal of providing deep insights into the exploitation of more precise and effective combinational therapy against cancer.
通讯机构：
[Yu, CY; Wei, H ] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
摘要：
Cyclic polymers with cleavable backbones triggered by either external or internal stimuli can realize simultaneous extracellular stability and intracellular destabilization of cyclic polymer-based nanocarriers but remain seldom reported. To this end, we prepared herein cyclic-ONB-P(OEGMA-st-DMAEMA) (c-ONB-P(OEGMA-st-DMAEMA)) with a light-cleavable junction in the polymer backbone based on oligo (ethylene glycol) monomethyl ether methacrylate (OEGMA) and N,N-dimethylaminoethyl methacrylate (DMAEMA) using a light-cleavable atom transfer radical polymerization (ATRP) initiator containing an o-nitrobenzyl (ONB) ester group. Together with the pH-sensitivity of DMAEMA, c-ONB-P(OEGMA-st-DMAEMA) shows a light-cleavable mainchain and pH-sensitive side chains. Notably, doxorubicin (DOX)-loaded c-ONB-P(OEGMA(4)-st-DMAEMA(38)) (C2) micelles mediated an IC(50) value of 2.28 μg/mL in Bel-7402 cells, which is 1.7-fold lower than that acquired without UV irradiation. This study thus reported the synthesis of a cyclic copolymer with a UV-cleavable backbone and uncovered the effects of topological modulation on the in vitro controlled release properties of cyclic polymers.
通讯机构：
[Li, CQ ] U;[Guo, MZ ] B;Univ South China, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;Beijing Univ Civil Engn & Architecture, Sch Elect & Informat Engn, Beijing 100044, Peoples R China.
摘要：
Transcription factors (TFs), transcription co-factors (TcoFs) and their target genes perform essential functions in diseases and biological processes. KnockTF 2.0 (http:////www.licpathway.net//KnockTF//index.html) aims to provide comprehensive gene expression profile datasets before//after T(co)F knockdown//knockout across multiple tissue//cell types of different species. Compared with KnockTF 1.0, KnockTF 2.0 has the following improvements: (i) Newly added T(co)F knockdown//knockout datasets in mice, Arabidopsis thaliana and Zea mays and also an expanded scale of datasets in humans. Currently, KnockTF 2.0 stores 1468 manually curated RNA-seq and microarray datasets associated with 612 TFs and 172 TcoFs disrupted by different knockdown//knockout techniques, which are 2.5 times larger than those of KnockTF 1.0. (ii) Newly added (epi)genetic annotations for T(co)F target genes in humans and mice, such as super-enhancers, common SNPs, methylation sites and chromatin interactions. (iii) Newly embedded and updated search and analysis tools, including T(co)F Enrichment (GSEA), Pathway Downstream Analysis and Search by Target Gene (BLAST). KnockTF 2.0 is a comprehensive update of KnockTF 1.0, which provides more T(co)F knockdown//knockout datasets and (epi)genetic annotations across multiple species than KnockTF 1.0. KnockTF 2.0 facilitates not only the identification of functional T(co)Fs and target genes but also the investigation of their roles in the physiological and pathological processes. Graphical Abstract
作者机构：
[Wu, Yimou; Li, Yuehua; Wu, YM] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Lijun; Zhu, Hongbo; Li, Yuehua; Tang, Yuanbin; Feng, Wenjie; Wan, Zhixing; Qi, Xiaowen; Xie, Liming; Zhu, HB] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[He, Rongfang] Univ South China, Affiliated Hosp 1, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, YM ; Zhu, HB ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.
关键词：
CircCRIM1;Environmental factors;Exosomes;Immune infiltration;OGA;Triple-negative breast cancer
摘要：
Triple-negative breast cancer (TNBC) has an escalating morbidity and a dismal prognosis. Obesity has been reported to be strongly linked to adverse TNBC outcomes. Exosomes (Exos) transport RNA and proteins between cells and serve as intermediaries for cell-to-cell communication. Accumulated evidence suggests that adipose-secreted circular RNAs (circRNAs) can modulate protein glycosylation in TNBC to facilitate tumor cell outgrowth. Herein, exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. Functional experiments demonstrated that by inhibiting miR-503-5p, exo-circCRIM1 enhanced TNBC evolution and metastasis while activating glycosylation hydrolase OGA. Furthermore, OGA negatively regulates FBP1 by decreasing its protein stability. Moreover, the levels of OGA and FBP1 were positively related to the infiltration level of some immune cells in TNBC. These findings indicate that exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503-5p and activating the OGA/FBP1 signaling pathway. The findings reveal a novel intercellular signaling pathway mediated by adipose-derived exosomes and suggest that treatment targeting the secreted exosome-circCRIM1 may reverse TNBC progression.
作者机构：
[Luo, Ying; Huang, Shiting; Zhou, Yishan; Tang, Shuangyang; Shen, Haiyan; Xiang, Jing] Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Key Lab Environm & Crit Human Dis Prevent,Educ Dep, Hengyang 421001, Peoples R China.
通讯机构：
[Shen, HY ] U;Univ South China, Inst Biochem & Mol Biol, Hengyang Med Coll, Key Lab Environm & Crit Human Dis Prevent,Educ Dep, Hengyang 421001, Peoples R China.
关键词：
Ursolic acid;Acute B lymphoblastic leukaemia;Apoptosis;Pyroptosis;JNK
摘要：
Objective: To explore the mechanism of ursolic acid (UA) against acute B lymphoblastic leukaemia (B-ALL) based on network pharmacological analysis, molecular docking and experimental verification.Methods: The core targets, functional processes, and biological pathways of UA in B-ALL were predicted by network pharmacology and molecular docking. The efficacy and mechanism of UA against B-ALL were verified through in vitro experiments such as cell viability assays, CCK-8 assays, LDH assays, AO/EB staining, flow cytometry, and Western blot assays.Results: Network pharmacology analysis of the core targets indicated that the effects of UA on B-ALL were related to programmed cell death (apoptosis and pyroptosis). Molecular docking results showed that FOS, CASP8, MAPK8, IL-1 beta and JUN were the key targets of UA against B-ALL. The MTS assay showed that UA decreased the viability of Reh cells in a concentration-and time -dependent manner. Cellular and Western blot experiments found that UA induced Reh cell apoptosis and pyroptosis by upregulating the JNK signalling pathwayConclusions: Our findings demonstrated that UA could induce Reh cell apoptosis and pyroptosis by activating the JNK signalling pathway to exert anti-B-ALL effects. This indicates that UA may become a potential drug for the effective treatment of B-ALL.
摘要：
As an integral organelle in the eukaryote, the lysosome is the degradation center and metabolic signal center in living cells, and partakes in significant physiological processes such as autophagy, cell death and cellular senescence. Fluorescent probe has become a favorite tool for studying organelles and their chemical microenvironments because of its high specificity and non-destructive merits. Over recent years, it has been reported that increasingly new lysosome-targeted probes play a major role in the diagnosis and monitor of diseases, in particular cancer and neurodegenerative diseases. In order to deepen the relevant research on lysosome, it is challenging and inevitability to design novel lysosomal targeting probes. This review first introduces the concepts of lysosome and its closely related biological activities, and then introduces the fluorescent probes for lysosome in detail according to different detection targets, including targeting mechanism, biological imaging, and application in diseases. Finally, we summarize the specific challenges and discuss the future development direction facing the current lysosome-targeted fluorescent probes. We hope that this review can help biologists grasp the application of fluorescent probes and broaden the research ideas of researchers targeting fluorescent probes so as to design more accurate and functional probes for application in diseases.
摘要：
Cancer is a malignant tumor that seriously threatens human life and health. At present, the main treatment methods include surgical resection, chemotherapy, radiotherapy, and immunotherapy. However, the mechanism of tumor occurrence and development is complex, and it produces resistance to some traditional treatment methods, leading to treatment failure and a high mortality rate for patients. Therefore, exploring the molecular mechanisms of tumor occurrence, development, and drug resistance is a very important task. MiRNAs are a type of non-coding small RNA that regulate a series of biological effects by binding to the 3′-UTR of the target mRNA, degrading the mRNA, or inhibiting its translation. MiR-1-3p is an important member of them, which is abnormally expressed in various tumors and closely related to the occurrence and development of tumors. This article introduces miR-1-3p from multiple aspects, including its production and regulation, role in tumor occurrence and development, clinical significance, role in drug resistance, and approaches for targeting miR-1-3p. Intended to provide readers with a comprehensive understanding of the important role of miR-1-3p in tumors.
作者机构：
[Ding, Yiteng; Zhong, Rongbin; Yang, Xuefeng; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang 421002, Hunan, Peoples R China.;[He, Longwei; Jiang, Renfeng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Hunan, Peoples R China.;[Yuan, Lin; He, Longwei; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.
通讯机构：
[Longwei He; Dan Cheng] H;Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang 421002, Hunan, China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
关键词：
acute kidney injury;fluorescent probe;near-infrared;peroxynitrite and glutathione;reversible imaging
摘要：
The multifunctional chemotherapeutic prodrugs that possess an effective combination of tumor targeting capability, activable chemotherapeutic activity, photodynamic therapy (PDT) assistance and near‐infrared fluorescence imaging (NIRFI) guidance are desirable to be engineered for real‐time monitoring of drug delivery, distribution, and synergistic chemo‐PDT in cancer treatment. Abstract Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor‐targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near‐infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real‐time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo‐drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging‐guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging‐guided therapy are provided.
