摘要：
Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized. Thus, this work provides a review of this emerging subject of research, focusing on immunomodulatory anticancer peptides. This review introduces the role of peptides in the immunomodulation of innate and adaptive immune cells, followed by a link between peptides in the innate and adaptive immune systems. The peptides are discussed in detail, following a classification according to their effects on different innate and adaptive immune cells, as well as immune checkpoints. Subsequently, two delivery strategies for peptides as drugs are presented: peptide self-assemblies and peptide-functionalized nanocarriers. The concluding remarks regarding the challenges and potential solutions of peptides for tumor immunotherapy are presented. This work introduces the role of peptides in immune regulation of innate and adaptive immune cells, as well as immune checkpoints. Then this work introduces two strategies for delivering polypeptides: peptide self-assemblies, and peptide-functionalized nanocarriers. Finally, the challenges and prospects of peptides in tumor immunotherapy are summarized. image
摘要：
Microcystin-LR (MC-LR) is a toxin that causes hepatic steatosis. Our previous study found that exposure to 60 μg/L MC-LR for 9 months resulted in liver lipid accumulation, but the underlying mechanisms remain elusive. Herein, for the first time, fatty acid-targeted metabolome and RNA-seq were combined to probe the effect and mechanism of chronic (12-month) MC-LR treatment on mice lipid metabolism at environmental-related levels (1, 60, and 120 μg/L). It was found that MC-LR dose-dependently raised serum and liver lipid levels. The total cholesterol (TC) levels in the liver were significantly increased following treatment with 1 μg/L MC-LR (equivalent to 0.004 μ/L in human). Treatment with 60 and 120 μg/L MC-LR significantly elevated TC and triglyceride (TG) levels in both serum and liver. Serum fatty acid-targeted metabolome analysis demonstrated that exposure to 1, 60, and 120 μg/L MC-LR caused significant alterations in the fatty acid profile. Chronic 1, 60, and 120 μg/L MC-LR treatment significantly increased serum polyunsaturated fatty acids (PUFAs), including conjugated linoleic acid and eicosapentaenoic acid, which positively correlated with serum or liver TG levels. Chronic exposure to 120 μg/L MC-LR led to a significant decrease in the accumulation of saturated fatty acids, including citramalic acid, pentadecanoic acid, and docosanoic acid, which were negatively correlated with serum or liver lipid levels. These findings suggested that 1 μg/L MC-LR exposure caused mild lipid metabolism disruption, while 60 and 120 μg/L MC-LR treatment resulted in pronounced hepatic steatosis in mice. Transcriptome analysis revealed that chronic environmental MC-LR treatment regulated the expression of genes involved in the phosphatidylinositol 3-kinase (PI3K) complex and fatty acid metabolism. Western blotting and RT-qPCR confirmed that chronic environmental MC-LR exposure activated the PI3K/AKT/mTOR signaling pathway, the downstream of fads3 gene that participates in fatty acid desaturation was upregulated, fatty acid degradation-related genes, including acsl1, acsl4, and ehhadh were inhibited, and lipid transport-related genes, including slc27a4 and apol7a, were promoted. Thus, chronic environmental MC-LR exposure boosts hepatic steatosis. Our work indicated that the limit concentration of 1 μg/L MC-LR in human drinking water for safety needs to be discussed. The study provides the first evidence of the fatty acid profile and gene changes and gains new insights into the mechanisms of chronic environmental MC-LR treatment-induced hepatic steatosis.
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD; Wu, GL] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
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作者机构：
[Liu, Ying; Deng, Min; Zhai, Zibo; He, Longwei; Wang, Peipei; Li, Songjiao; Cheng, Dan; He, LW] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch,Dept Gastroenterol, Hengyang 421002, Peoples R China.;[He, LW; He, Longwei] Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
通讯机构：
[He, LW ] H;[Li, SJ ; He, LW] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
摘要：
Revealing changes in the tumor microenvironment is crucial for understanding cancer and developing sensitive methods for precise cancer imaging and diagnosis. Intracellular hydrogen peroxide (H(2)O(2)) and microenvironmental factors (e.g., viscosity and polarity) are closely linked to various physiological and pathological processes, making them potential biomarkers for cancer. However, a triple-response theranostic probe for precise tumor imaging and therapy has not yet been achieved due to the lack of effective tools. Herein, we present a mitochondria-targeting near-infrared (NIR) fluorescent probe, VPH-5DF, capable of simultaneously monitoring H(2)O(2), viscosity, and polarity through dual NIR channels. The probe specifically detects H(2)O(2) via NIR emission (λ(em) = 650 nm) and shows high sensitivity to microenvironmental viscosity/polarity in the deep NIR channel (λ(em) ≈ 750 nm). Furthermore, the probe not only monitors mitochondrial polarity, viscosity, and fluctuations in endogenous/exogenous H(2)O(2) levels but also distinguishes cancer cells from normal cells through multiple parameters. Additionally, VPH-5DF can be employed to monitor alterations in H(2)O(2) levels, as well as changes in viscosity and polarity, during drug-induced pyroptosis in living cells. After treatment with VPH-5DF, chemotherapy-induced oxidative damage to the mitochondria in tumor cells activated the pyroptosis pathway, leading to a robust antitumor response, as evidenced in xenograft tumor models. Thus, this triple-response theranostic prodrug offers a new platform for precise in vivo cancer diagnosis and anticancer chemotherapy.
期刊：
Drug Design, Development and Therapy,2025年19:1655-1668 ISSN：1177-8881
通讯作者：
Long, MH;Xie, N
作者机构：
[Yan, Ting; Fu, Yilan; Zhang, Jiwen; Long, Minghui; Chen, Yun; Long, MH; Liao, Dehua] Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med,Dept Pahrm, Changsha, Peoples R China.;[Zhang, Jiwen] Univ South China, Sch Pharm, Hengyang 421001, Peoples R China.;[Xie, Ning] Cent South Univ, Hunan Canc Hosp, Med Dept Breast Canc, Affiliated Canc Hosp,Xiangya Sch Med, Changsha, Peoples R China.
通讯机构：
[Long, MH ; Xie, N ] C;Cent South Univ, Hunan Canc Hosp, Affiliated Canc Hosp, Xiangya Sch Med,Dept Pahrm, Changsha, Peoples R China.;Cent South Univ, Hunan Canc Hosp, Med Dept Breast Canc, Affiliated Canc Hosp,Xiangya Sch Med, Changsha, Peoples R China.
关键词：
T-DXd;AEs;ILD/pneumonitis;HER2;ADC
摘要：
Trastuzumab deruxtecan (T-DXd) has been approved to treat various tumors. While most adverse events (AEs) associated with T-DXd are manageable, interstitial lung disease (ILD)/pneumonitis is a notable AE of special concern. This review describes the incidence, severity, and management of T-DXd-induced ILD/pneumonitis across different tumors. We conducted a systematic search of PubMed, Embase, Cochrane Library, and Web of Science for literature published up to 13 September 2024, regarding the use of T-DXd in the treatment of HER2-positive tumors. Studies included were clinical trials involving HER2-positive tumors with reported ILD/pneumonitis cases.The main data extracted from the full-text articles included the incidence and severity of T-DXd-induced ILD. 18 studies involving 3380 patients with various advanced solid malignancies were included in our review. The overall incidence of adjudicated drug-related ILD/pneumonitis was 12.40%. Although most ILD/pneumonitis cases were low-grade, the risk of ILD/pneumonitis-related death should not be overlooked. Given the prolonged exposure to the drug, careful monitoring and management of T-DXd-induced ILD/pneumonitis are critical. Management strategies include dose reduction, treatment interruption, discontinuation, corticosteroids, and supportive care. Further research is needed to clarify the risk factors and mechanisms underlying T-DXd-induced ILD/pneumonitis. This review highlights critical gaps in understanding the risk factors and mechanisms of T-DXd-induced ILD, underscoring the need for further research.
摘要：
Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa ) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N -acetylcysteine-ε-poly- l -lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro . Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDR P. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.
Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa ) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N -acetylcysteine-ε-poly- l -lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro . Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDR P. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.
作者机构：
[Yuan, Peng-Xiang; Wang, Li-Li; Wang, Yu-Ping; Du, Fangfang] School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;[Du, Fangfang] Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma, Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, Hainan, China;[Yang, Liu-Pan] School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: yanglp@usc.edu.cn;[Wang, Li-Li] Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: wangll@usc.edu.cn
通讯机构：
[Li-Li Wang] S;School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China<&wdkj&>Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
摘要：
As widely used antibiotics, tetracycline residues exist in food and environmental media, which pose certain hidden dangers and negative effects on public health. Therefore, the sensing and discrimination of tetracycline analogs (TCs) have great significance for improving food safety and preventing environmental pollution. Herein, a 7-hydroxycoumarin-3-carboxylic acid-embedded Eu-MOF (HC@Eu-MOF) material was constructed and then developed for the detection of TCs. Upon addition of TCs, the synthesized sensor displays opposite fluorescence changes at two different wavelengths due to the simultaneous presence of the inner filter effect (IFE) and the antenna effect (AE), and achieves a stable ratio signal response within 90s. In addition, six important tetracycline analogs, including chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC), metacycline (MC), doxycycline (DC) and demeclocycline (DMC) can be discriminated with 100% accuracy through the principal component analysis even in extremely complicated mixtures. Further, a smartphone-assisted portable device was applied for visual sensing of TCs. The as-developed platform possessed the characteristics of simple synthesis, fast response, high sensitivity, and high stability, which further lays a further foundation for the on-site visual detection and discrimination of TCs in real samples.
摘要：
Cardiovascular diseases (CVDs), the leading cause of human death worldwide, are diseases that affect the heart and blood vessels and include arrhythmias, coronary atherosclerotic heart disease, hypertension, and so on. Resveratrol (RSV) is a natural nonflavonoid phenolic compound with antioxidant, anti-inflammatory, anticancer, and cardiovascular protection functions. RSV has shown significant protective effects against CVD. However, RSV's clinical application is limited by its tendency to be oxidized and metabolized easily. Therefore, it is necessary to optimize the RSV structure. This review will introduce the activity, synthesis, and structure-activity relationships of RSV derivatives, and the mechanism of the action of RSV in CVDs in recent years.
摘要：
There is relatively little research on cyclic amphiphilic block polymers, having both hydrophilic and hydrophobic segments placed in the ring and thus resulting in a higher degree of topological restriction, as drug vehicles. Cyclic amphiphilic binary block polymer is synthesized by the click coupling reaction of bimolecular homodifunctional precursors. The results indicate that cyclization between linear polymer precursors is successful if the trace linear by-products generated are ignored, which also suggests that the small molecule bifunctional terminating agent applied in traditional bimolecular homodifunctional ring-closure process can be extended to large molecule. Moreover, the study on the self-assembly behavior of polymers shows that, compared with linear counterparts, the stability and drug loading capacity of micelles based on the resultant cyclic polymer are not significantly improved due to the influence of topological structure and linear impurities. Nevertheless, drug loaded micelles formed by the obtained cyclic polymers still exhibit superior cellular uptake ability. It can be seen that topological effects do play an irreplaceable role in the application performance of polymers. Therefore, the construction and synthesis of cyclic and its derivative polymers with moderate topological confinement and high purity may be a key direction for future exploration of polymer drug delivery carriers.
作者机构：
[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Wang, Xuan; Song, Chao; Yu, Zhengmin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Wang, Xuan; Song, Chao; Yu, Zhengmin] Univ South China, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, Hengyang 421001, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Yu, Zhengmin] Univ South China, Hengyang Med Coll, Inst Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Wang, Xuan; Song, Chao; Yu, Zhengmin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Wang, Xuan; Song, Chao; Yu, Zhengmin] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Li, CQ ] U;[Guo, MZ ] B;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Sch, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Inst Biochem & Mol Biol, Hengyang 421001, Peoples R China.
关键词：
genes;genome-wide association study;rna, small cytoplasmic;datasets
摘要：
Identifying cell populations associated with risk variants is essential for uncovering cell-specific mechanisms that drive disease development and progression. Integrating genome-wide association studies (GWAS) with single-cell RNA sequencing (scRNA-seq) has become an effective strategy for detecting trait-cell relationships. The accumulation of trait-related single cell data has led to an urgent need for its comprehensively processing. To address this, we developed sc2GWAS (https://bio.liclab.net/sc2GWAS/), which aims to document large-scale GWAS trait-cell regulatory pairs at single-cell resolution and provide comprehensive annotations and enrichment analyses for these related pairs. The current version of sc2GWAS curates a total of 15 078 310 candidate trait-cell pairs from > 6 300 000 individual cells, offering a valuable resource for exploring complex regulatory relationships between traits and cells. We applied strict quality control measures on both scRNA-seq data and GWAS data, ensuring the reliability and accuracy of the datasets for the identification of trait-relevant cells and genes. In addition, sc2GWAS provides ranked lists of trait-relevant genes and extensive (epi) genetic annotations, making it a valuable resource for downstream analyses. We demonstrate the utility of the platform by investigating Alzheimer's disease, where we identified significant associations between the disease and microglial cells, with the APOE gene emerging as particularly significant. This platform facilitates detailed research into complex trait-cell and trait-gene interactions, we anticipate that sc2GWAS will become a comprehensive and valuable platform for exploring GWAS trait-cell regulatory mechanisms.<br /> [GRAPHICS] .
作者机构：
[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Hengyang Med Sch, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Yuexin; Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui; Zhang, Jianing; Song, Chao] Univ South China, Hunan Prov Key Lab Multiomics&Artificial Intellige, Hengyang 421001, Hunan, Peoples R China.;[Li, Ye; Yin, Mingxue; Li, Chunquan; Liu, Liyuan; Zhang, Guorui] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Li, Chunquan; Song, Chao] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, CQ ] U;[Guo, MZ ] B;Univ South China, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hunan Prov Key Lab Multiomics&Artificial Intellige, Hengyang 421001, Hunan, Peoples R China.
摘要：
It is challenging to identify regulatory transcriptional regulators (TRs), which control gene expression via regulatory elements and epigenomic signals, in context-specific studies on the onset and progression of diseases. The use of large-scale multi-omics epigenomic data enables the representation of the complex epigenomic patterns of control of the regulatory elements and the regulators. Herein, we propose Transcription Regulator Activity Prediction Tool (TRAPT), a multi-modality deep learning framework, which infers regulator activity by learning and integrating the regulatory potentials of target gene cis-regulatory elements and genome-wide binding sites. The results of experiments on 570 TR-related datasets show that TRAPT outperformed state-of-the-art methods in predicting the TRs, especially in terms of forecasting transcription co-factors and chromatin regulators. Moreover, we successfully identify key TRs associated with diseases, genetic variations, cell-fate decisions, and tissues. Our method provides an innovative perspective on identifying TRs by using epigenomic data. Here, the authors propose Transcription Regulator Activity Prediction Tool (TRAPT), a multi-modality deep learning framework, which infers regulator activity by learning and integrating the regulatory potentials of target gene cis-regulatory elements and genome-wide binding sites.
摘要：
Detergents are essential molecular tools for membrane protein (MP) research, yet traditional detergents with static properties often fail to address the diverse and evolving needs of MP studies. To this end, this study introduces "living detergents", an innovative class of detergents equipped with functional tags that enable bioorthogonal modifications with externally introduced structural elements. This approach allows for not only the parallel generation of new detergents, but also in situ tuning of MP samples within freshly formed detergents. The efficacy of this strategy was demonstrated through the rapid identification of optimal detergents for high-quality electron microscopy studies of A(2A)AR. Overall, this flexible and robust platform enables efficient tailoring of detergents, advancing the exploration of detergent structure-function relationships in MP research and opening pathways for more specialized solutions for diverse experimental demands.
摘要：
Funding Pyroptosis is a type of programmed cell death (PCD) pathway distinguished by inflammation. It is activated by specific inflammasomes. Once activated, it causes the physical breakdown of the cell, along with the discharge of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). Abundant evidence has demonstrated the existence of pyroptotic cell death within atherosclerotic plaques, which has significance for the development of atherosclerosis (AS). As a result, pyroptosis has become a new and important topic in cardiovascular disease (CVD) research. Cholesterol, it is recognized to have a connection with inflammation, exerts a crucial function in the development process of AS, and has been linked to the initiation of pyroptosis. This review aims to briefly summarize the fundamental aspects of pyroptosis and the influence of cholesterol-related inflammation in AS. Additionally, this review will explore potential therapeutic approaches based on pyroptosis that could be utilized for the prevention and treatment of AS.
摘要：
Tannic acid (TA) is the primary bioactive component in the gallnut (Galla chinensis) and has exhibited the anticancer effects. However, the mechanism of its anti-cancer activity in nasopharyngeal carcinoma (NPC) remains unclear. This research aims to explore the underlying mechanism of TA in the treatment of nasopharyngeal cancer using network pharmacology, molecular docking and experimental validation. Firstly, the targets of TA and NPC were predicted and collected through databases, and the intersection targets were identified. Subsequently, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics (MD) simulation were conducted to uncover the potential mechanisms of TA in treatment of NPC. Finally, in vitro experiments were utilized to verify the mechanism of TA with anticancer activity in NPC. The results of network pharmacology revealed 42 intersection targets between NPC-related targets and TA-related targets. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling was identified as the main target pathway of TA against NPC. Additionally, molecular docking and MD simulation confirmed the closely binding affinities of TA with AKT1. Furthermore, the results of in vitro experiments demonstrated that TA exerts anticancer activity against NPC by targeting the PI3K/AKT signaling pathway, leading to the suppression of cell proliferation. TA is a promising therapeutic candidate for NPC through PI3K/AKT signaling pathway. These results provide insights into the clinical application of TA, particularly when considered in combination with other therapeutic modalities.
摘要：
Aptamers have recently become novel probes for biosensors because of their good biocompatibility, strong specificity, and high sensitivity. Biosensors based on peptides or nucleic acid aptamers are used in implantable and wearable devices owing to their ease of synthesis and economic efficiency. Simultaneously, amphoteric ionic peptides are being explored as antifouling layers for biosensors resistant to interference from extraneous proteins in serum. Thus, this paper reviews recently developed aptamer-based biosensors and introduces peptide- and nucleic acid-based biosensors, while focusing on the three primary classes of biosensors: electrochemical sensors, fluorescent or colorimetric biosensors, and electroluminescent sensors. Furthermore, we summarize their general construction strategies, describe specific electrochemical sensors that use peptides as an antipollution layer, and elucidate their advantages.
摘要：
α‑1 Antitrypsin (AAT) is an acute phase protein encoded by the serine protease inhibitor family A member 1 gene. This multifunctional protein serves several roles, including anti‑inflammatory, antibacterial, antiapoptotic and immune regulatory functions. The primary role of AAT is to protect tissues and organs from protease‑induced damage due to its function as a serine protease inhibitor. AAT is associated with the development of lung inflammation, liver inflammation and immune‑mediated inflammatory diseases, which are influenced by environmental and genetic factors. For instance, AAT acts as an anti‑inflammatory protein to prevent and reverse type I diabetes. The present study briefly reviewed the molecular properties and mechanisms of AAT, as well as advances in the study of lung, liver and inflammatory diseases associated with AAT. The potential of AAT as a diagnostic and therapeutic target for inflammatory and immune‑mediated inflammatory diseases was reviewed. In addition, the damaging and protective effects of AAT, and its effects on organ function were discussed.
作者：
Wang, Xiaoman;Xie, Qian;Ke, Linling;Gong, Yuanhang;Li, Min
期刊：
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS,2025年(215) ISSN：1940-087X
通讯作者：
Li, M
作者机构：
[Ke, Linling; Li, Min; Xie, Qian; Li, M; Wang, Xiaoman; Gong, Yuanhang] Univ South China, Hengyang Med Sch, Inst Biochem & Mol Biol, Hengyang, Peoples R China.;[Li, Min; Li, M] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha, Peoples R China.
通讯机构：
[Li, M ] U;Univ South China, Hengyang Med Sch, Inst Biochem & Mol Biol, Hengyang, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss, Key Lab Birth Defect Res & Prevent, Changsha, Peoples R China.
摘要：
Replication stress induced by exposure to extrinsic agents can lead to DNA breaks at common fragile sites, which are regions in the genome known to be prone to structural instability. The gamma H2A.X chromatin immunoprecipitation (ChIP) assay serves as a powerful tool in genotoxicity studies, as gamma H2A.X phosphorylation is a well-established marker for DNA double-strand breaks. Traditional gamma H2A.X ChIP assays, however, are often labor-intensive and involve multiple, time-consuming steps. In this study, we present a simplified yet effective method that combines subcellular fractionation with native ChIP to isolate gamma H2A.X-associated complexes. This approach is particularly suitable for analyzing gamma H2A.X-chromatin interactions with enhanced specificity and efficiency. Using subcellular fractionation, chromatin-unbound materials are effectively removed, resulting in a purified chromatin fraction. Subsequent micrococcal nuclease (MNase) digestion under mild conditions allows chromatin fragmentation while preserving physiological interactions between gamma H2A.X and its associated protein complexes. This preservation is essential for studying native interaction partners involved in DNA damage response pathways. This optimized native ChIP protocol substantially reduces the time and labor associated with conventional gamma H2A.X ChIP assays. The streamlined procedure not only simplifies the workflow but also yields highly reproducible results, making it particularly advantageous in settings where high-throughput processing of multiple samples is required. This method has broad applicability in studies focused on genome stability, DNA repair, and chromatin biology, where accurate and efficient detection of DNA damage sites is critical. By employing optimized protocols and streamlined steps, this method enables the detection of DNA damage at fragile sites with improved sensitivity and minimal sample handling, making it a valuable tool for studies on genome stability and DNA damage response.
摘要：
Percutaneous coronary intervention (PCI) can effectively restore myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, STEMI patients may still experience a “no-reflow” phenomenon after PCI. Accordingly, this study focused on the clinical value of low-dose dobutamine stress myocardial contrast echocardiography (MCE) for evaluating myocardial microcirculation perfusion and long-term prognosis in STEMI patients after PCI. This study included 70 STEMI patients receiving PCI. Low-dose dobutamine stress MCE was performed to detect viable myocardium at 72 h after PCI and quantitatively analyze myocardial microcirculation perfusion at 72 h and 6 months after PCI. Patients were categorized into dobutamine stress echocardiography (DSE)-positive and DSE-negative groups, followed by comparisons of LVEF. The 3-year survival of STEMI patients after PCI was analyzed. No adverse reactions occurred during low-dose dobutamine stress MCE. Low-dose dobutamine stress MCE effectively detected viable myocardium at 72 h after PCI (AUC: of 0.849). Under the basal or stress state, A, β, and A × β values of viable myocardium at 6 months after PCI were prominently higher than values at 72 h after PCI. A and A × β values of viable myocardium at 6 months after PCI were considerably higher in the stress state than in the basal state. LVEF and long-term survival rates after PCI were markedly higher in the DSE-positive group than in the DSE-negative group. Low-dose dobutamine stress MCE is an effective evaluation method for myocardial perfusion, left ventricular function recovery, and poor long-term prognosis in STEMI patients after PCI.
期刊：
Life Sciences,2025年366-367:123461 ISSN：0024-3205
通讯作者：
Huang, Z;Chen, LX
作者机构：
[Liu, Duo; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang 421001, Peoples R China.;[Wang, Lingzhi] Jishou Univ, Affiliated Hosp 1, Dept Pharm, Jishou 416000, Hunan, Peoples R China.;[Huang, Zhen] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, 28 Changsheng West Rd, Hengyang, Hunan, Peoples R China.
通讯机构：
[Chen, LX ; Huang, Z ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, 28 Changsheng West Rd, Hengyang, Hunan, Peoples R China.
关键词：
Calcium homeostasis;Cardiovascular diseases;Nervous system diseases;Neural calcium sensor 1;cancer
摘要：
Neuronal calcium sensor 1 (NCS1) belongs to the family of neuronal calcium sensing proteins, which are distributed in various tissues of the human body, mainly in nerve tissues. NCS1 has multiple functions, including participating in the transduction of intracellular calcium signals, neuronal morphology, development and exocytosis. NCS1 performs related functions by interacting with a variety of proteins, including inositol 1,4,5-trisphosphate receptors (InsP3Rs), voltage-gated K + and Ca 2+ channels, phosphatidylinositol 4-kinase IIIβ (PI (4) KIIIβ). Over the years, researches on NCS1 and diseases have mostly focused on the nervous system and cardiovascular system, it is found that the abnormal expression of NCS1 is also related to cancer. Starting from the structure of NCS1 and the proteins that interact with it, this review expounds the mechanism or potential mechanism of NCS1 imbalance leading to various diseases.
Neuronal calcium sensor 1 (NCS1) belongs to the family of neuronal calcium sensing proteins, which are distributed in various tissues of the human body, mainly in nerve tissues. NCS1 has multiple functions, including participating in the transduction of intracellular calcium signals, neuronal morphology, development and exocytosis. NCS1 performs related functions by interacting with a variety of proteins, including inositol 1,4,5-trisphosphate receptors (InsP3Rs), voltage-gated K + and Ca 2+ channels, phosphatidylinositol 4-kinase IIIβ (PI (4) KIIIβ). Over the years, researches on NCS1 and diseases have mostly focused on the nervous system and cardiovascular system, it is found that the abnormal expression of NCS1 is also related to cancer. Starting from the structure of NCS1 and the proteins that interact with it, this review expounds the mechanism or potential mechanism of NCS1 imbalance leading to various diseases.
摘要：
NAD(P)H dehydrogenase quinone 1 (NQO1) is overexpressed in various cancers and is strongly associated with an immunosuppressive microenvironment and poor prognosis. In this study, we explored the role of NQO1 in the microenvironment, prognosis and immunotherapy of Hepatocellular carcinoma (HCC) using multi-omics analysis and machine learning. The results revealed that NQO1 was significantly overexpressed in HCC cells. NQO1(+)HCC cells were correlated with poor prognosis and facilitated tumor-associated macrophages (TAMs) polarization to M2 macrophages. We identified core NQO1-related genes (NRGs) and developed the NRGs-related risk-scores in hepatocellular carcinoma (NRSHC). The comprehensive nomogram integrating NRSHC, age, and pathological tumor-node-metastasis (pTNM) Stage achieved an area under the curve (AUC) above 0.7, demonstrating its accuracy in predicting survival outcomes and immunotherapy responses of HCC patients. High-risk patients exhibited worse prognoses but greater sensitivity to immunotherapy. Additionally, a web-based prediction tool was designed to enhance clinical utility. In conclusion, NQO1 may play a critical role in M2 polarization and accelerates HCC progression. The NRSHC model and accompanying tools offer valuable insights for personalized HCC treatment.
