期刊：
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY,2026年344(Pt 1):126623 ISSN：1386-1425
通讯作者：
Longwei He<&wdkj&>Songjiao Li
作者机构：
[Deng, Min; Ai, Siwei; Liu, Ying; Zhang, Hailin; Zhai, Zibo; Li, Songjiao] 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;Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, PR China;School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, PR China;[Cheng, Dan] 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<&wdkj&>Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, PR China;[He, Longwei] 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<&wdkj&>School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, PR China
通讯机构：
[Longwei He; Songjiao Li] 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 421002, 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<&wdkj&>School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, PR China
摘要：
In osteoarthritis , hypochlorous acid (HClO)—a critical biomarker of inflammation—and neutrophil elastase (NE)—a key mediator of inflammatory responses—undergo significant changes. Fluorescent probes , which offer high sensitivity and real-time visualization, have been widely employed for osteoarthritis imaging. However, most existing probes are designed to detect only a single biomarker, which can lead to false-positive signals in complex biological environments. In contrast, dual-locked fluorescent probes, which require activation by two distinct biomarkers, offer improved specificity and reliability. These probes are particularly advantageous for multiplexed detection in arthritis-related imaging. To date, no dual-responsive fluorescent probe targeting both HClO and NE has been reported. In this study, we introduce Cou-HN, a dual-locked fluorescent probe that exhibits a significant fluorescence enhancement at 470 nm only when both HClO and NE are present simultaneously. Neither HClO nor NE alone is sufficient to trigger a notable fluorescence response. This dual-activation strategy provides Cou-HN with superior imaging accuracy compared to single-locked probes. Both in vitro and in vivo experiments confirm its excellent performance, highlighting its promise for more precise diagnosis and monitoring of osteoarthritis.
In osteoarthritis , hypochlorous acid (HClO)—a critical biomarker of inflammation—and neutrophil elastase (NE)—a key mediator of inflammatory responses—undergo significant changes. Fluorescent probes , which offer high sensitivity and real-time visualization, have been widely employed for osteoarthritis imaging. However, most existing probes are designed to detect only a single biomarker, which can lead to false-positive signals in complex biological environments. In contrast, dual-locked fluorescent probes, which require activation by two distinct biomarkers, offer improved specificity and reliability. These probes are particularly advantageous for multiplexed detection in arthritis-related imaging. To date, no dual-responsive fluorescent probe targeting both HClO and NE has been reported. In this study, we introduce Cou-HN, a dual-locked fluorescent probe that exhibits a significant fluorescence enhancement at 470 nm only when both HClO and NE are present simultaneously. Neither HClO nor NE alone is sufficient to trigger a notable fluorescence response. This dual-activation strategy provides Cou-HN with superior imaging accuracy compared to single-locked probes. Both in vitro and in vivo experiments confirm its excellent performance, highlighting its promise for more precise diagnosis and monitoring of osteoarthritis.
期刊：
World Journal of Surgical Oncology,2025年23(1):1-2 ISSN：1477-7819
通讯作者：
Guo Wang
作者机构：
[Hai-Bo Zhang] Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China;[Ying Zeng] Department of Pharmacy, Hengyang Medical School, The Affiliated Changsha Central Hospital, University of South China, Changsha, China;[Guo Wang] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
通讯机构：
[Guo Wang] D;Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
作者机构：
[Xie, Zhizhong; Zou, Wei; Wang, Jiaying] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Sch Pharm, Hengyang 421001, Peoples R China.;[Gao, Yinhuang; Liu, Menghua; Miao, Zhishuo] Southern Med Univ, Sch Pharmaceut Sci, Key Lab Drug Metab Res & Evaluat State Drug Adm, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China.
通讯机构：
[Liu, MH ] S;[Zou, W ] U;Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Sch Pharm, Hengyang 421001, Peoples R China.;Southern Med Univ, Sch Pharmaceut Sci, Key Lab Drug Metab Res & Evaluat State Drug Adm, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China.
摘要：
Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its "double-edged sword" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.
摘要：
Background: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed composite indicator of atherogenic lipids. Nevertheless, few studies concern the relationship between NHHR and early-onset post-stroke depression (PSD). Methods: After two weeks of acute ischemic stroke (AIS), early-onset PSD was identified. The Hamilton Depression Scale-17 items (HAMD-17) was used to assess the severity of depression. Patients with HAMD-17 scores ≥7 were divided into an early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between NHHR and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the associations between the NHHR and early-onset PSD. Sensitivity analyses were performed to test the robustness of our findings. Receiver operating characteristic curve (ROC) analysis was used to determine the predictive value of the NHHR for early-onset PSD. Results: Among the 846 patients who were enrolled prospectively, a total of 283 (33.45%) patients were diagnosed with early-onset PSD. The NHHR showed a positive correlation with the HAMD-17 scores (r=0.498, P<0.001). A binary logistic regression model demonstrated that the NHHR (odds ratio [OR], 1.796; 95% confidence interval [CI] 1.452-1.996, P<0.001) was an independent factor for early-onset PSD. The NHHR for early-onset PSD had an area under the curve (AUC) value of 0.798. Conclusions: The findings suggest that the NHHR may be an independent risk factor for early-onset PSD, providing valuable insights for prevention and prognostic management in affected patients.
期刊：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2025年73(26):16011–16027 ISSN：0021-8561
通讯作者：
Bo Su
作者机构：
[Xinyi Guo; Bo Su] Institute of Pharmacy and Pharmacology, School of Pharmacy, Hengyang Medical School, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, China
通讯机构：
[Bo Su] I;Institute of Pharmacy and Pharmacology, School of Pharmacy, Hengyang Medical School, University of South China, Chang Sheng Xi Avenue 28, Hengyang, Hunan 421001, China
摘要：
Diallyl trisulfide (DATS), an organosulfur compound from the common food garlic, has been attracting attention by exhibiting low toxicity, tumor susceptibility, and, especially, multiple antitumor activities, despite its simple molecular structure. The mounting data suggest that the effects of DATS are related to its induction of oxidative stress cell death in various forms via reactive oxygen species (ROS), such as apoptosis, ferroptosis, autophagy, and pyroptosis. Disruption of redox equilibrium by DATS involves not only the induction of ROS generation but also the inhibition of ROS scavenging through modulation of antioxidant systems, which in turn affects the redox-dependent key molecules in the signaling pathways, consequently curbing the malignant behavior of cancers. Retracing the progress of DATS antitumor research in the past decade, we conduct an in-depth analysis of the multitarget mechanisms of DATS intervening in redox homeostasis. This review provides clues for future studies to further reveal its potential antitumor effects.
作者机构：
[Gao, Yuan; Tang, Shengsong; Zhao, Xuhong; Zhang, Mengxia; Liao, Shuxian; Li, Shengfen; Ning, Qian; Huang, Ruilei] Hunan Univ Med, Biomed Res Inst, Hunan Prov Key Lab Antibody Based Drug & Intellige, Huaihua, Peoples R China.;[Tang, Shengsong; Liao, Shuxian; Li, Shengfen; Ning, Qian] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Tang, Shengsong; Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha, Peoples R China.;[Gao, Yuan; Tang, Shengsong] Ningxia Med Univ, Dept Pharmacol, Yinchuan, Peoples R China.;[Ning, Qian] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha, Peoples R China.
通讯机构：
[Tang, SS ; Ning, Q ; Ning, Q] H;Hunan Univ Med, Biomed Res Inst, Hunan Prov Key Lab Antibody Based Drug & Intellige, Huaihua, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha, Peoples R China.;Ningxia Med Univ, Dept Pharmacol, Yinchuan, Peoples R China.
关键词：
C11orf53;glycolysis;metabolism;NCI-H526;small cell lung cancer
摘要：
Small cell lung cancer (SCLC), the most malignant subtype of lung cancer, is a major cause of death among lung cancer patients. Drug resistance, high recurrence, and limitations of surgery are all obstacles to SCLC treatment. Consequently, clarifying the underlying mechanism of SCLC progression and identifying potential targets for therapeutic intervention are of paramount significance for improving the clinical outcomes of SCLC patients. C11orf53 has been demonstrated to play a crucial role in the NCI-H526 cell activity. However, few studies have focused on how C11orf53 affects the activity of NCI-H526 cells and the corresponding regulatory pathways. Herein, our study shows that C11orf53 affects the viability and proliferation of SCLC NCI-H526 cells by influencing the glycolytic pathway. We established the C11orf53 overexpression and knockdown systems in the NCI-H526 cell line with C11orf53-specific small-interfering RNA and lentivirus to assess the effects of C11orf53 on the activity and proliferation of NCI-H526 cells. Furthermore, the NCI-H526 cells with C11orf53 knockdown and overexpression were utilized to elucidate the molecular mechanism of C11orf53. Our study shows that C11orf53 knockdown significantly reduced the viability and proliferation of NCI-H526 cells. Additionally, adenosine triphosphate levels, glucose consumption, lactate secretion, and the expression of key enzymes involved in the glycolytic pathway were markedly decreased in NCI-H526 cells. These findings confirmed that the effect of C11orf53 on the activity and proliferation of NCI-H526 cells is mediated by its role in regulating cellular glycolysis.
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.
期刊：
Molecular and Cellular Biochemistry,2025年480(4):2143-2157 ISSN：0300-8177
通讯作者：
Wang, J
作者机构：
[Jiang, Tingting] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Dept Clin Lab, Hengyang 421000, Peoples R China.;[Zeng, Qun] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421000, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
通讯机构：
[Wang, J ] C;Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
摘要：
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
摘要：
The major facilitator superfamily (MFS) type efflux pumps of Acinetobacter baumannii play important roles in antibiotic resistance. However, the molecular mechanism of these transporters remains poorly understood. To address the molecular basis of substrate polyspecificity mediated by multidrug MFS transporters, we compared the substrate binding modes of A. baumannii CraA with its well-studied homolog, Escherichia coli MdfA. MdfA and CraA share similar structural features, including a cavity accessible to drugs from the cytoplasm when these transporters adopt the inside-out conformation. This predominantly hydrophobic cavity contains several distinct titratable and hydrophilic residues. Through substitution analysis, we demonstrate that these polar residues within the CraA drug binding cavity contribute to the transport of all tested drugs, whereas mutations of hydrophobic residues result in altered drug recognition profiles. In addition to the known titratable residues E38 and D46, we identified E338 as the only titratable residue that plays a substrate-specific role, as it is required for efficient transport of norfloxacin, but not ethidium. Substitution of E338 with asparagine or glutamine changes substrate specificity, enabling specific recognition of phenicols and mitomycin C. Furthermore, we show that the aromaticity of Y42 is crucial for phenicol recognition, while general hydrophobicity at this position is critical for mitomycin C specificity. We propose that E338 and Y42 function as key substrate selectivity determinants in CraA. IMPORTANCE Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
The major facilitator superfamily (MFS) type efflux pumps of Acinetobacter baumannii play important roles in antibiotic resistance. However, the molecular mechanism of these transporters remains poorly understood. To address the molecular basis of substrate polyspecificity mediated by multidrug MFS transporters, we compared the substrate binding modes of A. baumannii CraA with its well-studied homolog, Escherichia coli MdfA. MdfA and CraA share similar structural features, including a cavity accessible to drugs from the cytoplasm when these transporters adopt the inside-out conformation. This predominantly hydrophobic cavity contains several distinct titratable and hydrophilic residues. Through substitution analysis, we demonstrate that these polar residues within the CraA drug binding cavity contribute to the transport of all tested drugs, whereas mutations of hydrophobic residues result in altered drug recognition profiles. In addition to the known titratable residues E38 and D46, we identified E338 as the only titratable residue that plays a substrate-specific role, as it is required for efficient transport of norfloxacin, but not ethidium. Substitution of E338 with asparagine or glutamine changes substrate specificity, enabling specific recognition of phenicols and mitomycin C. Furthermore, we show that the aromaticity of Y42 is crucial for phenicol recognition, while general hydrophobicity at this position is critical for mitomycin C specificity. We propose that E338 and Y42 function as key substrate selectivity determinants in CraA.
IMPORTANCE
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
期刊：
JOURNAL OF ORGANIC CHEMISTRY,2025年90(4):1656-1662 ISSN：0022-3263
通讯作者：
Lei, Zhengwen;Wang, Zhen;Zeng, YF;Wang, Z
作者机构：
[Shen, Lixian] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm,Hunan Prov Key Lab Basic & Clin Pharmac, Hengyang 421001, Hunan, Peoples R China.;[Shen, Lixian; Liu, Jie; Wang, Zhen; Peng, Xue; Lei, Zhengwen; Zeng, Yao-Fu; Lei, ZW] Univ South China, Affiliated Hosp 1, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhen] Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhen] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China.
通讯机构：
[Wang, Z; Zeng, YF ; Wang, Z ; Lei, ZW] U;Univ South China, Affiliated Hosp 1, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China.
摘要：
We report a photoredox-catalyzed three-component sulfonaminoalkynylation of alkenes with N -aminopyridine salts and potassium alkynyltrifluoroborate salts. This aminoalkylation reaction underwent a radial/polar crossover mechanism, which was distinguished from the previous reports. A variety of β-alkynylated sulfonamides were obtained in moderate to excellent yields. The versatility of this method was further evidenced by its successful application in modifying biological molecules in advanced stages of development.
We report a photoredox-catalyzed three-component sulfonaminoalkynylation of alkenes with N -aminopyridine salts and potassium alkynyltrifluoroborate salts. This aminoalkylation reaction underwent a radial/polar crossover mechanism, which was distinguished from the previous reports. A variety of β-alkynylated sulfonamides were obtained in moderate to excellent yields. The versatility of this method was further evidenced by its successful application in modifying biological molecules in advanced stages of development.
Download: Download high-res image (72KB) Download: Download full-size image
Download: Download high-res image (72KB) Download: Download full-size image
作者机构：
[Dai, Miao; Yan, Jialong; Xu, Si; Xi, Hanqing; Ou, Guifang; Li, Xiaoxue; Xue, Wen; Chen, Guang; Tang, Yonghong; Wang, Jiwu; Liu, Xuelian] Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Dai, Miao; Xu, Si; Xi, Hanqing; Ou, Guifang; Tang, Yonghong] Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Li, Xiaoxue] Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang 421002, China;[Luo, Si; Wei, Ping] Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
作者机构：
[Song, Zhijun; Zhang, Mengli; Tan, Zhien; Lu, Na; Jiang, Xing; Ou, Min; Wu, Fangfang; Ruan, Lijun; Liang, Ying] National Engineering Research Center for Southwest Endangered Medicinal Resources Development, Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning, Guangxi 530023, PR China;[Jiang, Xing] Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Department of Pharmacy, lnstitute of Pharmacy and Pharmacology, the Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China;[Tang, Guotao] Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China;[Quan, Haiyan] Hunan Polytechnic of Environment and Biology, Hengyang, Hunan 421001, PR China;[Wu, Fangfang] Engineering Research Center of Innovative Traditional Chinese, Zhuang and Yao Materia Medica, Ministry of Education, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, PR China. Electronic address: wffttn@163.com
通讯机构：
[Yang, Xiaonan] N;[Wu, Fangfang] E;Engineering Research Center of Innovative Traditional Chinese, Zhuang and Yao Materia Medica, Ministry of Education, Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, PR China. Electronic address:;National Engineering Research Center for Southwest Endangered Medicinal Resources Development, Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning, Guangxi 530023, PR China. Electronic address:
摘要：
Scutellarein, a flavonoid compound from the traditional Chinese herb Scutellaria baicalensis , exhibits inhibitory effects against hepatocellular carcinoma (HCC), but its clinical application is limited by relatively weak potency. To enhance its antitumor activity, we synthesized a novel derivative, 5,6,7-trimethoxy-4′-benzimidazolyl scutellarein 6b (TBS6b), by introducing antitumor pharmacophores—trimethoxyphenyl and benzimidazole—into the scutellarein scaffold. TBS6b demonstrated significantly improved anti-HCC activity both in vitro and in vivo. Cell-based assays, including colony formation, EdU staining, wound healing, transwell migration, and western blot analysis, demonstrated that TBS6b significantly inhibits HCC cell proliferation, migration, and invasion. Mechanistically, we employed proteomic and transcriptomic sequencing, along with western blot and qRT-PCR experiments, to predict and validate ACKR3 as the target of TBS6b. Molecular docking studies confirmed that TBS6b binds tightly to the ACKR3 protein. Additionally, with the aid of pharmacological tools, we established that TBS6b promotes the ubiquitination and degradation of ACKR3. Tissue microarray analysis and queries of public databases revealed that ACKR3 expression is elevated in HCC tissues compared to adjacent non-cancerous tissues, correlating closely with patient survival. By constructing cell lines with either silenced or overexpressed ACKR3 , we confirmed that ACKR3 promotes the proliferation, migration, and invasion of HCC. Finally, rescue experiments indicated that TBS6b exerts its anticancer effects primarily through targeting ACKR3 . These findings establish ACKR3 as a critical target through which TBS6b mediates its anticancer activity against HCC.
Scutellarein, a flavonoid compound from the traditional Chinese herb Scutellaria baicalensis , exhibits inhibitory effects against hepatocellular carcinoma (HCC), but its clinical application is limited by relatively weak potency. To enhance its antitumor activity, we synthesized a novel derivative, 5,6,7-trimethoxy-4′-benzimidazolyl scutellarein 6b (TBS6b), by introducing antitumor pharmacophores—trimethoxyphenyl and benzimidazole—into the scutellarein scaffold. TBS6b demonstrated significantly improved anti-HCC activity both in vitro and in vivo. Cell-based assays, including colony formation, EdU staining, wound healing, transwell migration, and western blot analysis, demonstrated that TBS6b significantly inhibits HCC cell proliferation, migration, and invasion. Mechanistically, we employed proteomic and transcriptomic sequencing, along with western blot and qRT-PCR experiments, to predict and validate ACKR3 as the target of TBS6b. Molecular docking studies confirmed that TBS6b binds tightly to the ACKR3 protein. Additionally, with the aid of pharmacological tools, we established that TBS6b promotes the ubiquitination and degradation of ACKR3. Tissue microarray analysis and queries of public databases revealed that ACKR3 expression is elevated in HCC tissues compared to adjacent non-cancerous tissues, correlating closely with patient survival. By constructing cell lines with either silenced or overexpressed ACKR3 , we confirmed that ACKR3 promotes the proliferation, migration, and invasion of HCC. Finally, rescue experiments indicated that TBS6b exerts its anticancer effects primarily through targeting ACKR3 . These findings establish ACKR3 as a critical target through which TBS6b mediates its anticancer activity against HCC.
摘要：
Pulmonary hypertension is a progressive vascular disease characterized by pulmonary vascular remodeling , with high mortality and poor prognosis despite advances in medical therapy. Recently, histone modification therapies for pulmonary hypertension have received more attention. Studies have shown that abnormal histone modifications and the enzymes responsible for these alterations can drive pulmonary vascular cell proliferation , migration, and anti-apoptosis by regulating chromatin structure and gene expression, thereby promoting pulmonary vascular remodeling in pulmonary hypertension. This review illustrates histone modifications, including methylation , acetylation , lactylation, and SUMOylation , and the enzymes responsible for these modifications, exploring their role and pathophysiological mechanism in pulmonary hypertension. In addition, the review summarizes the small molecule modulators currently under development and their efficacy in various preclinical models of pulmonary hypertension. Comprehending the function of histone modifications in pulmonary hypertension will help identify new biomarkers and molecular targets and facilitate personalized treatments for this severe disease.
Pulmonary hypertension is a progressive vascular disease characterized by pulmonary vascular remodeling , with high mortality and poor prognosis despite advances in medical therapy. Recently, histone modification therapies for pulmonary hypertension have received more attention. Studies have shown that abnormal histone modifications and the enzymes responsible for these alterations can drive pulmonary vascular cell proliferation , migration, and anti-apoptosis by regulating chromatin structure and gene expression, thereby promoting pulmonary vascular remodeling in pulmonary hypertension. This review illustrates histone modifications, including methylation , acetylation , lactylation, and SUMOylation , and the enzymes responsible for these modifications, exploring their role and pathophysiological mechanism in pulmonary hypertension. In addition, the review summarizes the small molecule modulators currently under development and their efficacy in various preclinical models of pulmonary hypertension. Comprehending the function of histone modifications in pulmonary hypertension will help identify new biomarkers and molecular targets and facilitate personalized treatments for this severe disease.
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.
Download: Download high-res image (284KB) Download: Download full-size image
Download: Download high-res image (284KB) Download: Download full-size image
摘要：
With the development of society and the economy, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major chronic disease in contemporary society. Finding a safe, effective, and economical diagnostic method is essential for the prevention of MASLD. Serum immunoglobulin is a protein produced by the B cells after the body is stimulated by an external antigen or pathogen. It is very interesting and valuable to explore the relationship between serum immunoglobulins and MASLD. Unfortunately, only a small number of studies have explored the relationship between serum immunoglobulins and MASLD. Therefore, we review the research progress of serum immunoglobulins in MASLD. At the same time, we also discuss the shortcomings of these studies. We hope this review will provide experience and reference for the prevention of MASLD in the future.
摘要：
Zinc (Zn(2+)) is an essential trace element that plays a crucial role in various biological functions. Aberrant Zn(2+) homeostasis may lead to the occurrence and development of diseases. Zinc transporters, primarily classified into two families in humans: the ZnT (SLC30A) family and the ZIP (SLC39A) family, are critical regulators of Zn(2+) homeostasis. The roles of ZnT-mediated Zn(2+) homeostasis in diseases are an active area of research. The ZnT family comprises ten members, belonging to four subfamilies, which are widely distributed in various tissues and subcellular organelles. ZnTs mediate directional Zn(2+) efflux, transporting cytoplasmic Zn(2+) into extracellular compartments or sequestering it within intracellular vesicles. Accumulating evidence has shown that ZnT dysregulation or ZnT mutations can disrupt Zn(2+) homeostasis, leading to the occurrence and development of diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In this review, we focus on the distribution and structure of ZnTs. Furthermore, we synthesize recent advances in ZnT-mediated regulation of Zn(2+) homeostasis in disease pathogenesis to guide the development of novel diagnostic and therapeutic strategies.
