通讯机构：
[Zeng-Ping Chen] S;State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, People’s Republic of China
关键词：
Single particle inductively coupled plasma mass spectrometry;Hybridization chain reaction;RecJ(f) exonuclease;Target recycling amplification;Biomarkers;DNA-templated metal nanoclusters
摘要：
A versatile triple cascade amplification strategy was developed for ultrasensitive simultaneous detection of multiple cancer biomarkers using single particle inductively coupled plasma mass spectrometry (spICP-MS). The triple cascade amplification strategy consisted of an enhanced RecJ(f) exonuclease-assisted target recycling amplification module, a hybridization chain reaction amplification module, and a signal amplification module based on DNA-templated multiple metal nanoclusters. In the enhanced RecJ(f) exonuclease-assisted target recycling amplification module, the DNA bases at the 5 & PRIME; ends of aptamers for specific recognition of biomarkers were deliberately replaced by the corresponding RNA bases to enhance amplification efficiency. The signal amplification module based on DNA-templated multiple metal nanoclusters was innovatively used to amplify the signals measured by spICP-MS and at the same time effectively suppress possible background interferences. The proposed spICP-MS platform achieved satisfactory quantitative results for both carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) in human serum samples with accuracy comparable to that of the commercial ELISA kits. Moreover, it has wide dynamic ranges for both CEA (0.01-100 ng/mL) and AFP (0.01-200 ng/mL). The limit of detection for CEA and AFP was 0.6 and 0.5 pg/mL, respectively. Compared with conventional biomarkers detection methods, the proposed spICP-MS platform has the advantages of operational simplicity, ultra-high sensitivity, wide dynamic range, and low background. Therefore, it is reasonable to expect that the proposed spICP-MS platform can be further developed to be a promising alternative tool for biomarker detection in fields of clinical diagnosis and biomedical research.
摘要：
Steroids are tetracyclic aliphatic compounds, and most of them contain carbonyl groups. The disordered homeostasis of steroids is closely related to the occurrence and progression of various diseases. Due to high structural similarity, low concentrations in vivo, poor ionization efficiency, and interference from endogenous substances, it is very challenging to comprehensively and unambiguously identify endogenous steroids in biological matrix. Herein, an integrated strategy was developed for the characterization of endogenous steroids in serum based on chemical derivatization, ultra-performance liquid chromatography quadrupole Exactive mass spectrometry (UPLC-Q-Exactive-MS/MS), hydrogen/deuterium (H/D) exchange, and a quantitative structure-retention relationship (QSRR) model. To enhance the mass spectrometry (MS) response of carbonyl steroids, the ketonic carbonyl group was derivatized by Girard T (GT). Firstly, the fragmentation rules of derivatized carbonyl steroid standards by GT were summarized. Then, carbonyl steroids in serum were derivatized by GT and identified based on the fragmentation rules or by comparing retention time and MS/MS spectra with those of standards. H/D exchange MS was utilized to distinguish derivatized steroid isomers for the first time. Finally, a QSRR model was constructed to predict the retention time of the unknown steroid derivatives. With this strategy, 93 carbonyl steroids were identified from human serum, and 30 of them were determined to be dicarbonyl steroids by the charge number of characteristic ions and the number of exchangeable hrdrogen or comparing with standards. The QSRR model built by the machine learning algorithms has an excellent regression correlation, thus the accurate structures of 14 carbonyl steroids were determined, among which three steroids were reported for the first time in human serum. This study provides a new analytical method for the comprehensive and reliable identification of carbonyl steroids in biological matrix.
摘要：
As a novel third-generation ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown excellent systemic and intracranial activity in non-small cell lung cancer (NSCLC) patients who carry sensitizing ALK-activating mutations and progress on first- and second-generation TKIs. In comparison with other ALK-TKIs, lorlatinib has a unique safety profile for hyperlipidemia and central nervous system adverse events. Lorlatinib-induced adverse events are well tolerated, permanent discontinuations are rarely reported, and dose modifications and/or standard medical therapy are useful for the management of adverse events. Our present study reviews the safety profile of lorlatinib as well as the relevant management strategies. Our present study aims to provide a practical guide for the scientific management and application of lorlatinib.
摘要：
L-Lysine (L-Lys) quantification in serum using a novel and highly selective amperometric biosensor has been reported. In this study, an efficient, enzyme-free, and simple anti-fouling biosensor was developed based on a self-screened peptide aptamer. A glassy carbon electrode (GCE) was used to construct anti-fouling interfaces by modifying its surface with polyaniline (PANI) polymer. The peptide aptamer, Cys-Pro-Pro-Pro-Pro-Arg-Glu-AsnIle-Gln-Arg-Leu-Thr, was then immobilized onto this electrode via an electroactive cysteine linker and its potential in the determination of L-Lys was examined. Under optimised experimental conditions, the peptide modified electrodes exhibited excellent anti-fouling and electrochemical sensing. The biosensor was effective in resisting biofouling in a wide range of serum samples and amino acid solutions, and its linear range for L-Lys detection ranged from 1 nM to 10 mM, with a comparatively lower detection limit (0.3 nM; S/N = 3). The antifouling biosensor could detect L-Lys in real serum samples, and this approach of designing peptide aptamers based low-fouling biosensors can easily be extended to the development of a bio-sensing platform system for a variety of other metabolites.
作者机构：
[Wang, Zhe; Zou, Yang; Wang, Z] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Yang, Xiaoyan; Xie, Zhizhong; Lei, Xiaoyong; Zou, Yang; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.;[Lu, Na] Univ South China, Sch Nursing, Hengyang Med Sch, 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：
[Wang, Z ; Tang, GT ] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.
摘要：
Simultaneous inhibition of tumor vasculature and the glycolysis pathway may be a targeted anti-tumor strategy to inhibit tumor nutrient supply. Flavonoids are natural products with strong biological activity, which inhibit hypoxia induction factor 1α (HIF-1α) regulating glycolysis and tumor angiogenesis, while salicylic acid can reduce the glycolysis level of tumor cells by inhibiting related rate-limiting enzymes. A series of salicylic acid-modified indole trimethoxy-flavone derivatives were designed and synthesized by introducing benzotrimethoxy-structure commonly used in blood vessel blockers, and their anti-tumor activities were evaluated. Among them, compound 8f exhibited significant anti-proliferative activity against two hepatoma cells, HepG-2 and SMMC-7721, with IC(50) values of 4.63 ± 1.13 μM and 3.11 ± 0.35 μM, respectively. Colony formation experiments also further verified its excellent in vitro anti-tumor activity. In addition, compound 8f showed the ability to induce apoptosis in SMMC-7721 cells in a concentration-dependent manner. After treatment with compound 8f, the expressions of the rate-limiting enzymes PKM2, PFKM, HK2 and tumor angiogenesis-related vascular endothelial growth factor of the glycolytic pathway were all down-regulated, and the lactate level in the hepatoma cell SMMC-7721 was significantly reduced. The morphology of the nucleus and tubulin was also observed to disperse gradually with the increase of compound 8f concentration. And compound 8f showed strong binding ability to tubulin. Our results suggest that the strategy of synthesizing the salicylic acid-modified indole flavone derivative 8f is a way to obtain active anti-tumor candidate compounds that may be further developed as targeted agents to inhibit tumor vasculature and glycolytic pathways.
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Canc Res Inst, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Hunan Prov Key Lab Tumor Microenv, Hengyang 421001, Peoples R China.;[Zhong, Rongbin; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang 421001, 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, 421001, PR 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
期刊：
Sensors and Actuators B-Chemical,2023年385:133696 ISSN：0925-4005
通讯作者：
Dan Cheng<&wdkj&>Longwei He
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Heat stroke is devastating pathology associated with a high morbidity and mortality rate. If heat cytotoxicity mechanisms are understood early, stroke-related diseases can be prevented or treated. Unfortunately, the details of lysosome's role in heat stroke remain poorly understood due to a lack of adequate tools. Recent studies indicate a correlation between lysosome HClO and the development of heat stroke. For better interpretation and treatment of heat stroke, the urgent and reliable real-time tools for tracking the correlation between HClO level and heat stroke is necessary. Herein, we present MB-HClO, a near-infrared (NIR) probe for rapidly detecting lysosome HClO. In addition to being an easy chemical to synthesize, MB-HClO shows remarkable selectivity and sensitivity to HClO. By applying MB-HClO to living cells, we have successfully monitored levels of both exogenous and endogenous HClO. Furthermore, this probe can distinguish inflammation from a normal brain state in LPS-induced neuroinflammation. Additionally, HClO can be measured non-invasively and visually for the first time in response to heat shock by imaging lysosome HClO increase. Therefore, MB-HClO is a promising candidate for research on heat stroke's complex biological mechanism.
通讯机构：
[Yunmei Liu] I;Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, Hunan Province 421001, PR China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, 28 Western Changshen Road, Hengyang City, Hunan Province 421001, PR China
摘要：
Photodynamic therapy is a promising novel tumor treatment method. In this study, novel porphyrin-chrysin photosensitizer derivatives were synthesized. Most of the compounds showed antitumor activity against human cervical cancer HeLa cells and human lung cancer A549 cells, among which compound 4c had the best photodynamic therapy effect on HeLa cells and A549 cells, with IC(50) values of 6.26μM and 23.37μM, respectively. Free-base porphyrin-chrysin derivatives bind to DNA through surface self-stacking, and zinc metalloporphyrin-chrysin derivatives bind to ct-DNA through intercalation. Notably, the tightness of compound binding to ct-DNA was positively correlated with its antitumor activity. What's more, three-dimensional quantitative conformation studies have shown that increasing the positive charge of the porphyrin ring and introducing a strong electron-withdrawing group at the meso position of the porphyrin ring at the para-position of the benzene ring or reducing the space volume of the compound can enhance the antitumor activity.
作者机构：
[Yao, Xu; Tang, Wei-Ying; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zheng, Xing] Hunan Vocat Coll Sci & Technol, Dept Pharm, Third Zhongyi Shan Rd, Changsha 410004, Hunan, Peoples R China.;[Lin, JH; Lin, Jin-Hong] Shanghai Univ, Innovat Drug Res Ctr, Dept Chem, Shanghai 200444, Peoples R China.;[Zheng, Qu-Tong] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Xiao, Ji-Chang; Lin, Jin-Hong; Lin, JH; Tang, Wei-Ying] Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Chinese Acad Sci, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.
通讯机构：
[Lin, JH ] S;[Xiao, JC ; Lin, JH] U;[Zheng, QT ] H;Shanghai Univ, Innovat Drug Res Ctr, Dept Chem, Shanghai 200444, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
摘要：
Owing to the ubiquity of the hydroxyl group, reductive deoxygenation of alcohols has become an active research area. The classic Barton–McCombie reaction suffers from a tedious two-step procedure. New efficient methods have been developed, but they have some limitations, such as a narrow substrate scope and the use of moisture-sensitive Lewis acids. In this work, we describe the Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols with NaBH4. The process is applicable to benzyl, allyl and propargyl alcohols, and also to primary and secondary alcohols, demonstrating a wide substrate scope and a good level of functional group tolerance. This protocol features convenient operation and low cost of all reagents.
通讯机构：
[Zhiqiang Mao] C;[Longwei He] H;College of Health Science and Engineering, Hubei University, Wuhan 430062, 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, China
期刊：
JOURNAL OF MEDICINAL CHEMISTRY,2023年66(10):6725-6742 ISSN：0022-2623
通讯作者：
Mi, Pengbing;Zheng, Xing;Lin, YW
作者机构：
[Lang, Jia-Jia; Mi, Pengbing; Lin, Ying-Wu; Zheng, Xing; Zheng, X] Univ South China, Hengyang Med Coll, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Tan, Yan; Mi, Pengbing; Lin, Ying-Wu; Chen, Limei; Zheng, Xing; Chen, Hongfei; Zheng, X] Univ South China, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Lang, Jia-Jia; Mi, Pengbing; Lin, Ying-Wu] Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.;[Wang, Xuechuan; Lv, You] Univ Sci & Technol, Coll Bioresources Chem & Mat Engn, Xian 710021, Shaanxi, Peoples R China.;[Lv, You] Xian Amazinggene Co Ltd, Xian 710026, Shaanxi, Peoples R China.
通讯机构：
[Mi, PB; Lin, YW ; Zheng, X] U;Univ South China, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;Univ South China, Key Lab Prot Struct & Funct Univ Hunan Prov, Hengyang 421001, Peoples R China.
摘要：
Developing selective inhibitors for Janus kinase 1 (JAK1) is a significant focus for improving the efficacy and alleviating the adverse effects in treating immune-inflammatory diseases. Herein, we report the discovery of a series of C-5 pyrazole-modified pyrrolopyrimidine derivatives as JAK1-selective inhibitors. The potential hydrogen bond between the pyrazole group and E966 in JAK1 is the key point that enhances JAK1 selectivity. These compounds exhibit 10- to 20-fold JAK1 selectivity over JAK2 in enzyme assays. Compound 12b also exhibits excellent JAK1 selectivity in Ba/F3-TEL-JAK cellular assays. Metabolism studies and the results of the hair growth model in mice indicate that compound 12b may be a viable lead compound for the development of highly JAK1-selective inhibitors for immune and inflammatory diseases.
摘要：
Starch‐binding domain‐containing protein 1 (STBD1) is a glycogen‐binding protein that is pivotal to glycogen transport and metabolism and consists of a hydrophobic N‐terminal, a glycogen‐binding C‐terminal, and two specific motifs. STBD1 is mainly found in skeletal muscle, cardiac muscle, and liver, and its subcellular localization is mainly found in the endoplasmic reticulum, mitochondria‐associated membranes, and Golgi apparatus. STBD1 is involved in biological processes such as glycophagy, glycogen accumulation, and lipid droplet formation, as well as in the pathogenesis of cardiovascular diseases, metabolic diseases, and cancer. Abstract Starch‐binding domain‐containing protein 1 (STBD1) is a glycogen‐binding protein discovered in skeletal muscle gene differential expression that is pivotal to cellular energy metabolism. Recent studies have indicated that STBD1 is involved in many physiological processes, such as glycophagy, glycogen accumulation, and lipid droplet formation. Moreover, dysregulation of STBD1 causes multiple diseases, including cardiovascular disease, metabolic disease, and even cancer. Deletions and/or mutations in STBD1 promote tumorigenesis. Therefore, STBD1 has garnered considerable interest in the pathology community. In this review, we first summarized the current understanding of STBD1, including its structure, subcellular localization, tissue distribution, and biological functions. Next, we examined the roles and molecular mechanisms of STBD1 in related diseases. Based on available research, we discussed the novel function and future of STBD1, including its potential application as a therapeutic target in glycogen‐related diseases. Given the significance of STBD1 in energy metabolism, an in‐depth understanding of the protein is crucial for understanding physiological processes and developing therapeutic strategies for related diseases.
摘要：
Background: Curcumin is a polyphenol compound extracted from plant turmeric with high pharmacological activities. The clinical application of curcumin is limited due to the shortcomings of poor water solubility, instability, and low bioavailability.<&wdkj&>Objective: Modifying the 4', 4''-bit of curcumin is an effective strategy to improve the pharmacological activity of curcumin.<&wdkj&>Conclusion: In this review, we focused on the strategy of synthesis, medicinal properties, and structurefunction relationship of 4', 4''-bit modified curcumin derivatives.
摘要：
Breast cancer is one of the most common malignant tumors with high mortality and poor prognosis in women. There is an urgent need to discover new therapeutic targets for breast cancer metastasis. Herein, we identified that Apolipoprotein C1 (APOC1) was up-regulated in primary tumor of breast cancer patient that recurrence and metastasis by immunohistochemistry (IHC). Kaplan-Meier Plotter database showed that high levels of APOC1 in breast cancer patients were strongly associated with worse overall survival (OS) and relapse-free survival (RFS). Mechanistically, APOC1 silencing significantly inhibits MAPK/ERK kinase pathway and restrains the NF-κB to decrease the transcription of target genes related to growth and metastasis in vitro. Based on this regulatory mechanism, we developed these findings into potential therapeutic drugs, glutathione (GSH) responsive nano-particles (NPs) were used for systemic APOC1 siRNA delivery, NPs (siAPOC1) silenced APOC1 expression, and subsequently resulted in positive anti-tumor effects in orthotopic and liver metastasis models in vivo. Taken together, GSH responsive NP-mediated siAPOC1 delivery was proved to be effective in regulating growth and metastasis in multiple tumor models. These findings show that APOC1 could be a potential biomarker to predict the prognosis of breast cancer patients and NP-mediated APOC1 silencing could be new strategies for exploration of new treatments for breast cancer metastasis.
期刊：
Dyes and Pigments,2023年211:111083 ISSN：0143-7208
通讯作者：
Li, S.;He, L.
作者机构：
[Wang, Peipei; Li, Songjiao] Univ South China, Ctr Mol Imaging Probe, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang Med Sch,Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Liu, Ying; Yang, Ke; He, Longwei; Li, Songjiao] Univ South China, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构：
[Songjiao Li] C;[Longwei He] D;Center for Molecular Imaging Probe, Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China<&wdkj&>Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, China
摘要：
A near-infrared methylene blue-based fluorogenic probe with an on/off activation ability has emerged as an important means to detect and monitor biological analytes and to understand the biological processes involved in understanding these analytes within cells and organisms. By using biomarker-activated methylene blue-based probes, it is possible to produce more precise results with a lower risk of photodamage to biological samples and fewer biological interferences in the background. This brief review aims to give a rigorous but concise account of recent developments in activatable methylene blue-based fluorogenic probes by reporting the significant accomplishments in that field. Several strategies for detecting and imaging disease-related biomarkers (such as ROS, RRS, enzymes, ions, and other related species) have been discussed and analyzed. Additionally, methylene blue-based fluoroscopic probes are emphasized for use in developing new methods to detect and image biomarkers to address potential challenges and opportunities.
作者机构：
[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Wang, Yuezhu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Xilong; Feng, Chenchen; Wang, Qiuyu; Bai, Xuefeng; Zhang, Jian; Wang, Yuezhu; Ai, Bo; Liu, Xinyu; Zhou, Liwei; Zhao, Jun; Li, Chunquan; Zhu, Jiang; Wang, Fan] Harbin Med Univ, Sch Med Informat, Daqing Campus, Daqing 163319, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Zhang, Guorui; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Wang, Qiuyu; Song, Chao; Li, Chunquan; Qian, Fengcui] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Inte, Hengyang 421001, Hunan, Peoples R China.;[Wang, Qiuyu; Li, Chunquan] Univ South China, Hunan Prov Base Sci & Technol Innovat Cooperat, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chunquan Li] T;The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>School of Medical Informatics, Daqing Campus, Harbin Medical University , Daqing 163319, China<&wdkj&>School of Computer, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China , Hengyang , Hunan 421001, China<&wdkj&>The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China<&wdkj&>Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China , Hengyang , Hunan 421001, China<&wdkj&>Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang , Hunan 421001, China
摘要：
Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including ‘Search SE by TF-based’, ‘Differential-Overlapping-SE analysis’ and ‘SE-based TF–Gene analysis’. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.
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; Hu, Haihong; Zhan, Wendi; Zhang, TL; Zhu, Hongxia] Univ South China, Hengyang Med Coll, Sch Pharm, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Taolan; Hu, Haihong; Zhang, TL] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Phase 1 Clin Trial Ctr, Hengyang 421000, Hunan, Peoples R China.;[Zou, Mingxiang] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Spine Surg, Hengyang 421000, Hunan, Peoples R China.;[Hu, Hongjuan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Publ Hlth Serv, 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, Phase 1 Clin Trial Ctr, Hengyang 421000, Hunan, Peoples R China.
摘要：
This study sought to identify molecular subtypes of breast cancer (BC) and develop a breast cancer stem cells (BCSCs)-related gene risk score for predicting prognosis and assessing the potential for immunotherapy. Unsupervised clustering based on prognostic BCSC genes was used to determine BC molecular subtypes. Core genes of BC subtypes identified by non-negative matrix factorization algorithm (NMF) were screened using weighted gene co-expression network analysis (WGCNA). A risk model based on prognostic BCSC genes was constructed using machine learning as well as LASSO regression and multivariate Cox regression. The tumor microenvironment and immune infiltration were analyzed using ESTIMATE and CIBERSORT, respectively. A CD79A+CD24-PANCK+-BCSC subpopulation was identified and its spatial relationship with microenvironmental immune response state was evaluated by multiplexed quantitative immunofluorescence (QIF) and TissueFAXS Cytometry. We identified two distinct molecular subtypes, with Cluster 1 displaying better prognosis and enhanced immune response. The constructed risk model involving ten BCSC genes could effectively stratify patients into subgroups with different survival, immune cell abundance, and response to immunotherapy. In subsequent QIF validation involving 267 patients, we demonstrated the existence of CD79A+CD24-PANCK+-BCSC in BC tissues and revealed that this BCSC subtype located close to exhausted CD8+FOXP3+ T cells. Furthermore, both the densities of CD79A+CD24-PANCK+-BCSCs and CD8+FOXP3+T cells were positively correlated with poor survival. These findings highlight the importance of BCSCs in prognosis and reshaping the immune microenvironment, which may provide an option to improve outcomes for patients.
