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.
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.
摘要：
Chemodynamic therapy (CDT), as an emerging therapeutic strategy, kills cancer cells by converting in-tracellular hydrogen peroxide (H2O2) into cytotoxic oxidizing hydroxyl radicals ( center dot OH). However, the ther-apeutic efficiency of CDT is compromised due to the insufficient endogenous H2O2 and metal catalysts in tumor cells. The use of multivalent polyphenols with multiple hydroxyl functions provides a facile yet robust means for efficient CDT augmentation. For this purpose, we reported herein the construc-tion of polyphenol-metal nanoparticles (NPs) via a phenol-metal coordination strategy. The unique-ness of this study is the preparation of only one polymer construct with multivalency that can afford various supramolecular interactions for simultaneous "one-pot" loading of different therapeutic species, i.e., doxorubicin (DOX), glucose oxidases (GOD), and Fe3 + and further co-self-assembly into a stabilized nanomedicine for cascade amplified chemo-chemodynamic therapy. Specifically, the tumor intracellular acidic pH-triggered DOX release could serve for chemotherapy as well as enhance the intracellular H2O2 level. Together with the extra H2O2 and gluconic acid produced by the GOD-triggered glucose consump-tion, DOX@POAD-Fe@GOD NPs promoted Fe3+participation in the Fe-mediated Fenton reaction for cascade amplified chemo-chemodynamic therapy. Notably, this formulation displayed a greater anti-tumor effect with a tumor inhibition ratio 1.6-fold higher than that of free DOX in a BALB/c mice model bearing 4T1 tumors. Overall, the multivalent polyphenol-metal nanoplatform developed herein integrates chemother-apy, starvation therapy, and CDT for synergistic enhanced anticancer efficiency, which shows great poten-tial for clinical translations. Statement of significance Chemodynamic therapy (CDT) generally suffers from compromised therapeutic efficiency due to insuf-ficient endogenous H2O2 and metal catalysts in tumor cells. To develop a facile yet robust strategy for efficient CDT augmentation, we reported herein construction of a multivalent polyphenol-metal nanoplat-form, DOX@POAD-Fe@GOD nanoparticles (NPs) via a phenol-metal coordination strategy. This nanoplat-form integrates multiple supramolecular dynamic interactions not only for simultaneously safe encapsu-lation of doxorubicin (DOX), Fe3 +, and glucose oxidases (GOD), but also for cascade amplified chemo-chemodynamic therapy. Specifically, the intracellular acidic pH-triggered dissociation of DOX@POAD-Fe@GOD NPs promoted the release of Fe3 +, DOX, and GOD for significantly increased ROS levels that can accelerate Fenton reactions for cascaded chemotherapy, starvation therapy, and CDT with amplified antitumor efficiency in vivo .(c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
摘要：
Inflammation is a complex biological response triggered when an organism encounters internal or external stimuli. These triggers activate various signaling pathways, leading to the release of numerous inflammatory mediators aimed at the affected tissue. Ensuring precision and avoiding the excessive activation, the inflammatory process is subject to tight regulation. Histone deacetylase 3 (HDAC3), a member of class I HDACs family, stands out for its significant role in modulating various inflammatory signaling, including Nuclear Factor kappa B (NF-κB) signaling, Mitogen-activated protein kinase (MAPK) signaling and Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling. In this review, we illuminate the intricate molecular mechanisms of HDAC3 across these inflammatory pathways. We emphasize its importance in orchestrating a balanced inflammatory response and highlight its promising potential as a therapeutic target.
期刊：
Biosensors and Bioelectronics,2024年249:116002 ISSN：0956-5663
通讯作者：
Wang, WG
作者机构：
[Tan, Ting; Wang, Weiguo; Yang, Lin; Cao, Qianqian; Liu, Aizhe; Chen, Lijing; Deng, Yuqian] Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.;[Li, Ranhui; Duan, Minghui] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.
通讯机构：
[Wang, WG ] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.
关键词：
Ferrous disulfide;Nickel doping;Oxidase mimics;Total antioxidant capacity;Transition metal sulfides
摘要：
The development of nanomaterials that mimic oxidase-like activities has recently attracted an increasing amount of attention. Obtaining highly active and cost-effective oxidase mimics has posed a significant challenge in this area of research. In this study, we successfully synthesized nickel-doped ferrous disulfide nanocubes (Ni-FeS(2)) via a facile one-step method. Characterization by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Ni was predominantly distributed within the surface layer of the Ni-FeS(2) nanocubes. The incorporation of nickel in density functional theory (DFT) calculations effectively reduced the d-band center of Fe, resulting in weakened adsorption to intermediates and thereby enhancing its catalytic efficiency. Moreover, we developed a novel approach based on Ni-FeS(2) (the Ni-FeS(2) method) for detecting reducing substances, which exhibited good sensitivity toward ascorbic acid (AA), glutathione (GSH), and cysteine (Cys). Remarkably, the established Ni-FeS(2) method was successfully employed for in vitro assessment of total antioxidant capacity (TAC) in cellular and organ samples, thereby enabling discrimination between normal, senescent, and malignant cells as well as distinguishing among healthy liver tissue, cancerous liver tissue, and metastatic organs.
摘要：
Ferroptosis is a newly recognized type of regulated cell death that is characterized by the accumulation of iron and lipid peroxides in cells. Studies have shown that ferroptosis plays a significant role in the pathogenesis of various diseases, including cardiovascular diseases. In cardiovascular disease, ferroptosis is associated with ischemia-reperfusion injury, myocardial infarction, heart failure, and atherosclerosis. The molecular mechanisms underlying ferroptosis include the iron-dependent accumulation of lipid peroxidation products, glutathione depletion, and dysregulation of lipid metabolism, among others. This review aims to summarize the current knowledge of the molecular mechanisms of ferroptosis in cardiovascular disease and discuss the potential therapeutic strategies targeting ferroptosis as a treatment for cardiovascular disease.
摘要：
Tripterygium wilfordii Hook F (TwHF) has a long history of use as a traditional Chinese medicine and has been widely administered to treat various inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are endogenous, short, non-coding RNAs that regulate gene expression post-transcriptionally. They participate in the efficacies and even toxicities of the components of TwHF, rendering miRNAs an appealing therapeutic strategy. This review summarizes the recent literature related to the roles and mechanisms of miRNAs in the pharmacological and toxicological effects of main components of TwHF, focusing on two active compounds, triptolide (TP) and celastrol (CEL). Additionally, the prospects for the "You Gu Wu Yun" theory regarding TwHF nephrotoxicity are presented.
摘要：
L<bold>-</bold>Tryptophan (L-Trp), one of the essential amino acids, is crucial for human physiological homeostasis and a limiting amino acid in animal feed. In addition, L-Trp is a precursor of some important biomolecules in the body, such as pentraxin and melatonin. Disorders of L-Trp metabolism in the body may cause Alzheimer's or Parkinson's disease. Therefore, monitoring L-Trp levels in the body fluids quickly and accurately is essential. A colorimetric biosensor was developed for the rapid detection of L-Trp in solutions by coupling a novel, screened, and validated peptide aptamer with Au nanoparticles via the Au-S bond. The biosensor showed a wide linear detection range of 1 mu M - 1000 mu M, and in addition, it was simple to construct, and the reaction time was as short as 10 s. In the analysis of L-Trp in actual porcine serum samples, the relative standard deviations were 4.52 % to 3.01 % compared with those of the high-performance liquid chromatography method, and the spiked recoveries were 99.2 % to 100.2 %. This new type of recognition probe is likely to gain attention in the field of bioanalysis owing to its biocompatibility, ease of modification, and easy linkage to nanomaterials.
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：
[Tan, Huaxin; Hu, Lidan; Wei, Xiaojie; Li, Yongzhen; Ma, Jiaying] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Basic Med,Key Lab Ecol Environm & Crit Human D, Dept Biochem & Mol Biol,Dept Educ, Hengyang 421001, Peoples R China.;[Jiang, Suhua; Wang, Peiyuan; Ma, Jiaying] Chinese Acad Sci, Fujian Inst Res Struct Matter, Key Lab Design & Assembly Funct Nanostruct, Fuzhou 350002, Peoples R China.;[Jiang, Suhua; Zhu, Fukai] Minnan Normal Univ, Collaborat Innovat Ctr Mushroom Hlth Ind, Zhangzhou 363000, Fujian, Peoples R China.;[Ji, Xiaoxuan] Xiamen Univ, Sch Pharmaceut Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.;[Wang, Peiyuan] Chinese Acad Sci, Xiamen Inst Rare Earth Mat, Dept Translat Med, Xiamen 361021, Peoples R China.
通讯机构：
[Huaxin Tan] D;[Peiyuan Wang] K;Department of Biochemistry and Molecular Biology, the Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Basic Medicine, University of South China, Hengyang 421001, PR China<&wdkj&>Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, PR China<&wdkj&>Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361021, PR China
摘要：
Tyrosine-protein phosphatase non-receptor type 2(PTPN2), an important member of the protein tyrosine phosphatase family, can regulate various signaling pathways and biological processes by dephosphorylating receptor protein tyrosine kinases. Accumulating evidence has demonstrated that PTPN2 is involved in the occurrence and development of atherosclerotic cardiovascular disease. Recently, it has been reported that PTPN2 exerts an anti-atherosclerotic effect by regulating vascular endothelial injury, monocyte proliferation and migration, macrophage polarization, T cell polarization, autophagy, pyroptosis, and insulin resistance. In this review, we summarize the latest findings on the role of PTPN2 in the pathogenesis of atherosclerosis to provide a rationale for better future research and therapeutic interventions.
