作者机构：
[Chu, Chun] Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China;[Nie, Liangui; Hu, Hongming; Liu, Shengquan] Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China;[Liu, Yi] Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China. Electronic address: xiziju48262422@163.com;[Yang, Jun] Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China. Electronic address: weidongyang@mailfence.com
通讯机构：
[Liu, Yi; Yang, Jun] D;Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China. Electronic address:;Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China,Hengyang,Hunan Province 421001,China. Electronic address:
摘要：
BACKGROUND: Through bioinformatics analysis, this study explores the interactions and biological pathways involving metabolomic products in patients diagnosed with coronary heart disease (CHD). METHODS: A comprehensive search for relevant studies focusing on metabolomics analysis in CHD patients was conducted across databases including CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Nature, Web of Science, Springer, and Science Direct. Metabolites reported in the literature underwent statistical analysis and summarization, with the identification of differential metabolites. The pathways associated with these metabolites were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular annotation of metabolites and their relationships with enzymes or transporters were elucidated through analysis with the Human Metabolome Database (HMDB). Visual representation of the properties related to these metabolites was achieved using Metabolomics Pathway Analysis (metPA). RESULTS: A total of 13 literatures satisfying the criteria for enrollment were included. A total of 91 metabolites related to CHD were preliminarily screened, and 87 effective metabolites were obtained after the unrecognized metabolites were excluded. A total of 45 pathways were involved. Through the topology analysis (TPA) of pathways, their influence values were calculated, and 13 major metabolic pathways were selected. The pathways such as Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism primarily involved the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression. CONCLUSION: Multiple pathways, including Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism, were involved in the occurrence of CHD. The occurrence of CHD is primarily associated with the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression.
作者机构：
[Wu, Min; Song, Zhiyin; He, H; Chen, Li; He, He; Liu, Bing; Meng, Qingtao; Ye, Fei; Dong, Jun; Lin, Jiacheng; Tang, Junhui; Zhou, Pang-Hu] Wuhan Univ, Renmin Hosp, Coll Life Sci, TaiKang Ctr Life & Med Sci,Frontier Sci Ctr Immuno, Wuhan, Hubei, Peoples R China.;[Song, Zhiyin; He, H; Chen, Li; He, He] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathol, Wuhan, Hubei, Peoples R China.;[Song, Zhiyin; He, H; Chen, Li; He, He] Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Wuhan, Hubei, Peoples R China.;[Lu, Bin] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;[Lu, Jia-Hong] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.
通讯机构：
[Song, ZY; He, H ] W;Wuhan Univ, Renmin Hosp, Coll Life Sci, TaiKang Ctr Life & Med Sci,Frontier Sci Ctr Immuno, Wuhan, Hubei, Peoples R China.;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathol, Wuhan, Hubei, Peoples R China.;Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Wuhan, Hubei, Peoples R China.
摘要：
Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid beta-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis. The molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, authors uncover a role for the EMC2- SLC25A46-Mic19 axis in mitochondrial lipid metabolism and liver disease
期刊：
Clinical Drug Investigation,2024年44(3):199-207 ISSN：1173-2563
通讯作者：
Fu, CX
作者机构：
[Pan, Wei; Li, Dan; Chen, Danjun; Fu, Chengxiao; Yang, Bo; Yang, Xiongwen] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Pan, Wei; Li, Dan; Chen, Danjun; Wang, Lili; Fu, Chengxiao; Yang, Bo; Yang, Xiongwen] Univ South China, Hengyang Med Sch, Inst Pharm & Pharmacol, Coll Basic Med Sci, Hengyang 421200, Hunan, Peoples R China.;[Fu, Chengxiao] Univ South China, Affiliated Hosp 1, Clin Pharmacol Res Ctr, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Tong, Qin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Fu, CX ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Inst Pharm & Pharmacol, Coll Basic Med Sci, Hengyang 421200, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Clin Pharmacol Res Ctr, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要：
Background and ObjectivesAlthough thromboembolic events (TEEs) have been reported with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), their association remains largely unknown. In this study, we aimed to provide a comprehensive review of TEEs associated with EGFR-TKIs.MethodsWe collected EGFR-TKIs (gefitinib, erlotinib, afatinib, and osimertinib) adverse reaction reports from 2015 Q1 to 2023 Q1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Disproportionality analysis was conducted to identify thromboembolic adverse events associated with EGFR-TKIs by comparing them with the overall FAERS database according to the reporting odds ratio (ROR). Associated factors were explored using univariate logistic regression.ResultsWe identified 1068 reports of TEEs associated with EGFR-TKIs (1.24% accounts for all TEEs). Affected patients were females (49.72%) and those older than 65 years (41.20%). The reported TEE case fatality was 30.24%. The median time to onset (TTO) of all cases was 39 days [interquartile range (IQR) 11-161], and the median TTO of fatalities [31 days (IQR 10-116)] was significantly shorter than that of non-fatal cases [46 days (IQR 12-186)].ConclusionThis study yielded three key findings. Firstly, EGFR-TKIs seem to exhibit prothrombotic effects, elevating the risk of TEEs. Secondly, the clinical outcomes of TEEs associated with EGFR-TKIs were poor. Thirdly, most TEEs occurred within the initial 3 months, and fatal cases occurred earlier than non-fatal cases.
期刊：
Computational and Structural Biotechnology Journal,2024年23:77-86 ISSN：2001-0370
通讯作者：
Zhang, Jian;Zhu, J;Li, CQ
作者机构：
[Zhang, Jian; Gao, Yu; Zhao, Jun; Zhu, Jiang; Zhang, J] Harbin Med Univ, Sch Med Informat, Daqing Campus, Daqing 163319, Peoples R China.;[Wang, Qiuyu; Li, Chunquan; Song, Chao] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.;[Feng, Chenchen; Wang, Qiuyu; Song, Chao; Yin, Mingxue; Li, Chunquan] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Wang, Qiuyu; Song, Chao; Yin, Mingxue; Li, Chunquan] Univ South China, Hunan Prov Key Lab Multiomics&Artificial Intellige, Hengyang 421001, Hunan, Peoples R China.;[Wang, Qiuyu; Yin, Mingxue; Li, Chunquan] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, CQ ] U;[Zhang, J; Zhu, J ] H;Harbin Med Univ, Sch Med Informat, Daqing Campus, Daqing 163319, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.
关键词：
Single cell integration database;Cell heterogeneity;Multi-method automatic cell-type annotation;Cell to cell communication
摘要：
Single-cell RNA sequencing (scRNA-seq), which profiles gene expression at the cellular level, has effectively explored cell heterogeneity and reconstructed developmental trajectories. With the increasing research on diseases and biological processes, scRNA-seq datasets are accumulating rapidly, highlighting the urgent need for collecting and processing these data to support comprehensive and effective annotation and analysis. Here, we have developed a comprehensive Single -Cell transcriptome integration database for human and mouse (SCInter, https://bio.liclab.net/SCInter/index.php), which aims to provide a manually curated database that supports the provision of gene expression profiles across various cell types at the sample level. The current version of SCInter includes 115 integrated datasets and 1016 samples, covering nearly 150 tissues/cell lines. It contains 8016,646 cell markers in 457 identified cell types. SCInter enabled comprehensive analysis of cataloged single-cell data encompassing quality control (QC), clustering, cell markers, multi-method cell type automatic annotation, predicting cell differentiation trajectories and so on. At the same time, SCInter provided a user-friendly interface to query, browse, analyze and visualize each integrated dataset and single cell sample, along with comprehensive QC reports and processing results. It will facilitate the identification of cell type in different cell subpopulations and explore developmental trajectories, enhancing the study of cell heterogeneity in the fields of immunology and oncology.
摘要：
In recent years, there has been a growing interest in antimicrobial peptides as innovative antimicrobial agents for combating drug-resistant bacterial infections, particularly in the fields of biofilm control and eradication. In the present study, a novel cationic antimicrobial peptide, named LC-AMP-F1, was derived from the cDNA library of the Lycosa coelestis venom gland. The sequence, physicochemical properties and secondary structure of LC-AMP-F1 were predicted and studied. LC-AMP-F1 was tested for stability, cytotoxicity, drug resistance, antibacterial activity, and antibiofilm activity in vitro compared with melittin, a well-studied antimicrobial peptide. The findings indicated that LC-AMP-F1 exhibited inhibitory effects on the growth of various bacteria, including five strains of multidrug-resistant bacteria commonly found in clinical settings. Additionally, LC-AMP-F1 demonstrated effective inhibition of biofilm formation and disruption of mature biofilms. Furthermore, LC-AMP-F1 exhibited favorable stability, minimal hemolytic activity, and low toxicity towards different types of eukaryotic cells. Also, it was found that the combination of LC-AMP-F1 with conventional antibiotics exhibited either synergistic or additive therapeutic benefits. Concerning the antibacterial mechanism, scanning electron microscopy and SYTOX Green staining results showed that LC-AMP-F1 increased cell membrane permeability and swiftly disrupted bacterial cell membranes to exert its antibacterial effects. In summary, the findings and studies facilitated the development and clinical application of novel antimicrobial agents.
作者机构：
[Feng, Wen-Jie; Wu, Xiao-Ping; Zhu, Hong -Bo; He, Zhi-Long; Tan, Ye-Ru; Xun, Yi; Li, Yue-Hua; Jiang, Yi-Ling; Zhu, HB] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.;[Jiang, Bao-Hong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zhu, HB ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.
关键词：
AIFM2;GPX4;circRNAs;hepatocellular cancer (HCC);miR-6085
摘要：
BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.
期刊：
CURRENT PHARMACEUTICAL BIOTECHNOLOGY,2024年25(6):655-664 ISSN：1389-2010
作者机构：
Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P.R. China;Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P.R. China;NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Pharmacy School of Fudan University, Shanghai, 200032, P.R. China;[Hu, Xiangyan; Ye, Shiying] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P.R. China ;[Huang, Sisi] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, P.R. China <&wdkj&> NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Pharmacy School of Fudan University, Shanghai, 200032, P.R. China
摘要：
Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has received a rising attention for its remarkable roles in cancer therapy. In recent years, increasing evidence have revealed that oridonin inhibits the occurrence and development of tumor cells through multiple mechanisms, including induction of apoptosis and autophagy, cell cycle arrest, and inhibition of angiogenesis as well as migration and invasion. In addition, several molecular signal targets have been identified, including ROS, EGFR, NF-κB, PI3K/Akt, and MAPK. In this paper, we review considerable knowledge about the molecular mechanisms and signal targets of oridonin, which has been studied in recent years. It is expected that oridonin may be developed as a novel anti-tumor herbal medicine in human cancer treatment.
通讯机构：
[Wang, PY; Liu, XL ] C;Chinese Acad Sci, Key Lab Design & Assembly Funct Nanostruct, Fujian Inst Res Struct Matter, Fuzhou 350002, Peoples R China.;Fujian Agr & Forestry Univ, Coll Life Sci, Fuzhou 350002, Peoples R China.;Hosp Fujian Med Univ, United Innovat Mengchao Hepatobiliary Technol Key, Mengchao Hepatobiliary, Fuzhou 350025, Peoples R China.
摘要：
Triggering the healing process of drug-resistant bacteria-infected wounds has attracted great attention due to global morbidity that may induce gangrene, amputation, and even death. Here, a chitin derivative, carboxymethyl chitosan (CMC), tannic acid (TA), and Cu(2+) were used for hydrogel engineering. Using sodium bicarbonate as the neutralizer and reductant, hydrogen bonds between CMC and TA and in situ Cu(OH)(2) generation via ion coordination force between Cu(2+) and TA facilitated the synthesis of CMC/TA/Cu hydrogel. Cu(2+) and TA release, cytotoxicity, in vitro cell migration, angiogenesis, and antidrug-resistant bacteria were measured. Besides, wound closure was evaluated in vivo using the methicillin-resistant Staphylococcus aureus (MRSA)-infected excisional dermal wound mouse model. Negligible toxicity was observed both in vitro and in vivo. Dermal cell migration and angiogenesis were significantly enhanced. In vivo, the CMC/TA/Cu hydrogel induced effective re-epithelialization, collagen deposition, inflammatory alleviation, and MRSA inhibition during wound repair in mice. All these results confirmed that the CMC/TA/Cu hydrogel is a promising novel dressing for chronic wound healing in clinic.
摘要：
As an important characteristic of tumor, acidic tumor microenvironment (TME) is closely related to immune escape, invasion, migration and drug resistance of tumor. The acidity of the TME mainly comes from the acidic products produced by the high level of tumor metabolism, such as lactic acid and carbon dioxide. pH regulators such as monocarboxylate transporters (MCTs), carbonic anhydrase IX (CA IX), and Na+/H+ exchange 1 (NHE1) expel protons directly or indirectly from the tumor to maintain the pH balance of tumor cells and create an acidic TME. We review the functions of several pH regulators involved in the construction of acidic TME, the structure and structure-activity relationship of pH regulator inhibitors, and provide strategies for the development of small-molecule antitumor inhibitors based on these targets.
摘要：
Metabolism is reprogrammed in a variety of cancer cells to ensure their rapid proliferation. Cancer cells prefer to utilize glycolysis to produce energy as well as to provide large amounts of precursors for their division. In this process, cancer cells inhibit the activity of pyruvate dehydrogenase complex (PDC) by upregulating the expression of pyruvate dehydrogenase kinases (PDKs). Inhibiting the activity of PDKs in cancer cells can effectively block this metabolic transition in cancer cells, while also activating mitochondrial oxidative metabolism and promoting apoptosis of cancer cells. To this day, the study of PDKs inhibitors has become one of the research hotspots in the field of medicinal chemistry. Novel structures targeting PDKs are constantly being discovered, and some inhibitors have entered the clinical research stage. Here, we reviewed the research progress of PDKs inhibitors in recent years and classified them according to the PDKs binding sites they acted on, aiming to summarize the structural characteristics of inhibitors acting on different binding sites and explore their clinical application value. Finally, the shortcomings of some PDKs inhibitors and the further development direction of PDKs inhibitors are discussed.
期刊：
CHEMISTRY-AN ASIAN JOURNAL,2024年19(4):e202301036- ISSN：1861-4728
通讯作者：
Tan, Xiaofeng;Yang, QL
作者机构：
[Xiao, Hao; Yang, Qinglai; Tan, Xiaofeng; Wu, Gui-long; Yang, QL; Tan, Senyou] Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;[Xiao, Hao; Yang, Qinglai; Tan, Xiaofeng; Wu, Gui-long; Yang, QL; Tan, Senyou] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, 28 West Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;[Yang, Qinglai; Tan, Xiaofeng; Yang, QL] Hunan Prov Maternal & Child Hlth Care Hosp, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, 53 Xiangchun Rd, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Tan, XF; Yang, QL ] U;Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, 28 West Changsheng Rd, Hengyang City 421001, Hunan, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, 53 Xiangchun Rd, Changsha 410008, Hunan, Peoples R China.
关键词：
Tumor microenvironment factors;NIR-II phototheranostic agents;Simultaneous activation;Integration of diagnosis and treatment
摘要：
This review examines the recent advances in developing dual‐functional NIR‐II activatable phototheranostic agents over the past years. It systematically presents NIR‐II phototheranostic agents activated by various TME factors such as acidity (pH), hydrogen peroxide (H2O2), glutathione (GSH), hydrogen sulfide (H2S), enzymes, as well as multiple TME factors. Abstract Malignant tumors seriously threaten human life and well‐being. Emerging Near‐infrared II (NIR‐II, 1000–1700 nm) phototheranostic nanotechnology integrates diagnostic and treatment modalities, offering merits including improved tissue penetration and enhanced spatiotemporal resolution. This remarkable progress has opened promising avenues for advancing tumor theranostic research. The tumor microenvironment (TME) differs from normal tissues, exhibiting distinct attributes such as hypoxia, acidosis, overexpressed hydrogen peroxide, excess glutathione, and other factors. Capitalizing on these attributes, researchers have developed TME‐activatable NIR‐II phototheranostic agents with diagnostic and therapeutic attributes concurrently. Therefore, developing TME‐activatable NIR‐II phototheranostic agents with diagnostic and therapeutic activation holds significant research importance. Currently, research on TME‐activatable NIR‐II phototheranostic agents is still in its preliminary stages. This review examines the recent advances in developing dual‐functional NIR‐II activatable phototheranostic agents over the past years. It systematically presents NIR‐II phototheranostic agents activated by various TME factors such as acidity (pH), hydrogen peroxide (H2O2), glutathione (GSH), hydrogen sulfide (H2S), enzymes, and their hybrid. This encompasses NIR‐II fluorescence and photoacoustic imaging diagnostics, along with therapeutic modalities, including photothermal, photodynamic, chemodynamic, and gas therapies triggered by these TME factors. Lastly, the difficulties and opportunities confronting NIR‐II activatable phototheranostic agents in the simultaneous diagnosis and treatment field are highlighted.
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.
关键词：
gated blood-pool imaging;chromatin;genetics;mice;enhancer of transcription;candidate disease gene;single nucleotide polymorphism;crispr;genes;rna;genome;methylation
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：
BACKGROUND: The cellular endoplasmic reticulum (ER) is responsible for various functions, including protein synthesis, folding, distribution, and calcium ion storage. Studies have linked ER stress with acute lung injury (ALI), which can result in oxidative stress and even cell death. Peroxynitrite (ONOO(-)) is a well-known reactive oxygen species (ROS) that contributes to various physiological and pathological processes in oxidative stress diseases. To understand the role of ER ONOO(-) in ALI, it is crucial to accurately measure its level in the ER. Unfortunately, there is currently no probe available to detect ER ONOO(-) in an ALI model. RESULTS: To address this, we developed three near-infrared (NIR) fluorescent probes (DCM-F-ONOO, DCM-Cl-ONOO, and DCM-Br-ONOO) for the detection of ONOO(-) using pentafluorobenzenesulfonate (PFBS) moieties as fluorescence quenchers. Through comprehensive testing, we selected DCM-Br-ONOO as the best NIR fluorescent probe due to its rapid response (within 3min), high selectivity, good sensitivity (LOD=2.3nM), and approximately 66-fold enhanced response to ONOO(-) in fluorescence intensity. The probe was successfully applied to detect changes in ONOO(-) levels induced by different drugs in the ER of living cells. Importantly, a significant increase in the level of ONOO(-) was observed in the ER of an ALI cell model (4.5-fold) and an ALI mouse model (2.5-fold) using the probe, which is essential for understanding the role of ONOO(-) in ER-associated diseases. SIGNIFICANCE: Using DCM-Br-ONOO as a probe, present work further validated that the elevated levels of ONOO(-) secretion were accompanied by the ALI progressed. These findings may provide valuable results for figuring out the biological roles that ONOO(-) played in ALI.
期刊：
PATHOLOGY RESEARCH AND PRACTICE,2024年253:155042 ISSN：0344-0338
通讯作者：
Lian, Gaojian;Su, ZH
作者机构：
[Li, Zheng; Lian, Gaojian; Su, Zehong; Gong, Huifang; Wu, Zhimin] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Lian, GJ; Su, ZH ] U;Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Biomarker;Cancer therapy;Ferroptosis;NcRNAs;Programmed cell death
摘要：
Ferroptosis is a recently discovered cell programmed death. Extensive researches have indicated that ferroptosis plays an essential role in tumorigenesis, development, migration and chemotherapy drugs resistance, which makes it become a new target for tumor therapy. Non-coding RNAs (ncRNAs) are considered to control a wide range of cellular processes by modulating gene expression. Recent studies have indicated that ncRNAs regulate the process of ferroptosis via various pathway to affect the development of cancer. However, the regulation network remains ambiguous. In this review, we outlined the major metabolic processes of ferroptosis and concluded the relationship between ferroptosis-related ncRNAs and cancer progression. In addition, the prospect of ncRNAs being new therapeutic targets and early diagnosis biomarkers for cancer by regulating ferroptosis were presented, and the possible obstacles were also predicted. This could help in discovering novel cancer early diagnostic methods and therapeutic approaches.
期刊：
Journal of Advanced Research,2024年 ISSN：2090-1232
通讯作者：
Hu, Haoliang;Chen, Linxi
作者机构：
[Wang, Jin; Hu, Haoliang] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China;[Jiang, Jinyong] Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou 416000, China;[Hu, Haoliang] College of Medicine, Hunan University of Arts and Science, Changde 415000, China. Electronic address: huhl@huas.edu.cn;[Chen, Linxi] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China. Electronic address: 1995001765@usc.edu.cn
通讯机构：
[Haoliang Hu; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China<&wdkj&>College of Medicine, Hunan University of Arts and Science, Changde 415000, China<&wdkj&>Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China
摘要：
BACKGROUND: Globally, the onset and progression of multiple human diseases are associated with mitochondrial dysfunction and dysregulation of Ca(2+) uptake dynamics mediated by the mitochondrial calcium uniporter (MCU) complex, which plays a key role in mitochondrial dysfunction. Despite relevant studies, the underlying pathophysiological mechanisms have not yet been fully elucidated. AIM OF REVIEW: This article provides an in-depth analysis of the current research status of the MCU complex, focusing on its molecular composition, regulatory mechanisms, and association with diseases. In addition, we conducted an in-depth analysis of the regulatory effects of agonists, inhibitors, and traditional Chinese medicine (TCM) monomers on the MCU complex and their application prospects in disease treatment. From the perspective of medicinal chemistry, we conducted an in-depth analysis of the structure-activity relationship between these small molecules and MCU and deduced potential pharmacophores and binding pockets. Simultaneously, key structural domains of the MCU complex in Homo sapiens were identified. We also studied the functional expression of the MCU complex in Drosophila, Zebrafish, and Caenorhabditis elegans. These analyses provide a basis for exploring potential treatment strategies targeting the MCU complex and provide strong support for the development of future precision medicine and treatments. KEY SCIENTIFIC CONCEPTS OF REVIEW: The MCU complex exhibits varying behavior across different tissues and plays various roles in metabolic functions. It consists of six MCU subunits, an essential MCU regulator (EMRE), and solute carrier 25A23 (SLC25A23). They regulate processes, such as mitochondrial Ca(2+) (mCa(2+)) uptake, mitochondrial adenosine triphosphate (ATP) production, calcium dynamics, oxidative stress (OS), and cell death. Regulation makes it a potential target for treating diseases, especially cardiovascular diseases, neurodegenerative diseases, inflammatory diseases, metabolic diseases, and tumors.
作者机构：
[Guo, Zifen; Chen, Shang; Yang, Gun; Liao, Ke] Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China;[Huang, Xin; Chen, Shang; Yang, Gun; Liao, Ke; Yin, Lei; Liu, Quan; Long, Shoubin; Wang, Tianyuan; Wang, Jing] Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen University, Shenzhen, 518052, PR China;[Chen, Shang] Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, PR China;[Huang, Xin] Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230032, PR China;[Zou, Qingshuang] Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China
关键词：
Black phosphorus;Dendritic cells;Liver cancer;Photothermal therapy;Tertiary lymphatic structures
摘要：
Cellular immunotherapy is a crucial aspect of current tumor immunotherapy, though it presents several challenges such as immune cell dysfunction, limited recognition of neoantigens, and inadequate lymphocyte infiltration into the tumor microenvironment. This study proposes a novel approach utilizing a combination of dendritic cell (DC)-based cellular immunotherapy and a photothermal nanoadjuvant black phosphorus (BP) nanoparticles to overcome these challenges. A new platform called PLGA@BP-R848, which consists of modifying poly-(lactic-co-glycolic acid) (PLGA) onto BP nanosheets loading the immune adjuvant R848. The PLGA@BP-R848 nanoparticles demonstrated exceptional drug delivery and release capabilities, as well as a photothermal effect, biocompatibility, and the ability to activate the mitochondrial apoptotic pathway Blc-2-Bax-Cytochrome c-caspase-3 and inhibit the PI3K-AKT-mTOR signaling pathway. In a hepatocellular carcinoma mouse model, the binding of PLGA@BP-R848 nanoparticles and dendritic cells primed with GPC3 peptides, successfully induced a systemic anti-tumor immune response. PLGA@BP-R848 nanoparticles bolster immune cell infiltration into tumors and induce cancer cell apoptosis. The synergistic therapy involving dendritic cells and photothermal nanoadjuvant effectively suppressed tumor growth, and facilitated the formation of tertiary lymphatic structures (TLS) in tumors. This study presents a novel approach in using photothermal nanoadjuvants to advance antitumor effect of cellular immunotherapy, such as DCs therapy.
摘要：
The signal pathway of TNF‐α inducing human umbilical vascular endothelial cells apoptosis. Abstract Endothelial cell apoptosis driven by inflammation (TNF‐α) 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‐α 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‐α exposure. Real‐time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF‐α 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‐α on HUVECs, but downregulation of miR‐29a using anti‐miR‐29a blocked up its apoptotic effect. MiR‐29a inhibited the expression of PI3Kp85α and Bcl‐2 and blocked up the signal transduction of PI3K/AKT/Bcl‐2 axis to mediate the apoptotic effect of TNF‐α 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.
摘要：
BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.
期刊：
Journal of Hazardous Materials,2024年464:132986 ISSN：0304-3894
通讯作者：
Wang, JK
作者机构：
[Zhu, Yanli] Hunan Univ Technol & Business, Sch Resources & Environm, Changsha 410205, Hunan, Peoples R China.;[Wang, Jikai; Xie, Zhulan; Wang, JK; Sun, Yiyang; Zeng, Pengfei] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Chen, Danjun; Fu, Chengxiao] Univ South China, Affiliated Hosp 1, Hengyang Clin Pharmacol Res Ctr, Hengyang Med Sch,Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Yuehua] Hengyang Anim Husb & Aquaculture Affairs Ctr, Dept Anim Husb & Aquaculture Prod Qual Control, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wang, JK ] U;Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
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.
