摘要：
Alkaline phosphatase (ALP) is an indicator of sterilization efficacy of milk products and its activity monitoring is essential for ensuring food safety and controlling product quality. Here, a novel fluorometric method for the determination of ALP activity based on resorcinol monophosphate ester (RME) as a new substrate was proposed to verify pasteurization of milk products. RME was cheap and was simply and novelly synthesized by a two-step method using resorcinol (RC) as the raw material. The mechanism is, after dephosphorylation, RME was transformed to RC, which subsequently react with dopamine (DA) to form a strong fluorescent product, azamonardine. It has a fluorescence emission wavelength at 461 nm under the optimal excitation at 418 nm. The results show that under the optimum conditions, there is a good linear relationship between & UDelta;F (the variation of fluorescence intensity) and ALP activity over 0-5000 mU/L. High sensitivity was achieved (detection limit of 17.34 mU/L) because of high quantum yield of the products and catalytic activity of ALP and the recovery rate is 96.8-106.1%. Compared with national and international standard methods, the detection procedures are simple, just adding RME and DA solution to milk with buffer solution. Our method was successfully applied for ALP activity detection in milk products. Moreover, the catalyst of ALP and the reaction of RME and dopamine are pH dependent, and thus the reaction time could be kept identical by terminating the reaction through adding acids. With high sensitivity, high selectivity, simple operation, and wide linear range, our assay will find more practical applications in food analysis.
期刊：
Sensors and Actuators B-Chemical,2023年379:133253 ISSN：0925-4005
通讯作者：
He, LW;Cheng, D
作者机构：
[He, LW; 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：
[He, LW ; Cheng, D ] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
摘要：
Hypochlorous acid (HClO) is a key signal molecule involved in various physiological and pathological processes as well as the immune system. Recent study demonstrated that excess HClO in the body is closely related to diabetes since it can induce stress in the endoplasmic reticulum (ER). Unfortunately, up to now, developing a near-infrared (NIR) fluorescent probe that can detect ER HClO remains a challenge. Herein, we designed and synthesized NIR-ER-HClO, which stains ER with high selectivity, sensitivity, and hypotoxicity. The probe could accurately monitor exogenous and endogenous HClO variations in living cells. Besides, NIR-ER-HClO was successfully used to image HClO in a diabetic mice model. Compared with the control group, NIR-ER-HClO showed a stronger NIR fluorescence signal in diabetic mice and in the blood of people with diabetes. Thus, NIR-ER-HClO provides an effective method for diagnosing ER HClO in related diseases.
摘要：
Ursolic acid (UA) is a pentacyclic triterpenoid with diverse biological activities, especially in the fields of cardiovascular and diabetes treatment. However, its application is hindered by low bioavailability and poor solubility in water. Consequently, reseacher have focused on designing UA derivatives to address these issues. This paper provides an overview of the development of UA derivatives and their recent advancements as regents for combating cardiovascular diseases and diabetes. Abstract Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti‐cardiovascular and anti‐diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti‐diabetes anti‐cardiovascular reagents.
作者：
Wang Wen-jing;Wang Yi-fu;Jin Ya-jie;Song Wu-qiang;Lin Jia-meng;...
期刊：
农业科学学报(英文),2023年22(1):320-324 ISSN：2095-3119
作者机构：
[Wang Wen-jing; Tu Jian; Wang Yi-fu] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Wang Wen-jing; Tong Xin-ru; Jin Ya-jie; Lin Jia-meng; Zhang Yan; Wang Yi-fu; Li Tao; Song Wu-qiang] Chinese Acad Agr Sci, Shanghai Vet Res Inst, Shanghai 200241, Peoples R China.;[Tu Jian] Guilin Med Univ, Guilin 541199, Peoples R China.;[Li Rui-chao] Yangzhou Univ, Coll Vet Med, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China.
摘要：
An extensively drug-resistant (XDR) Escherichia coli strain 258E was isolated from an anal swab sample of a chicken farm of Anhui Province in China. Genomic analyses indicated that the strain 258E harbors an incompatibility group N (IncN) plasmid pEC258-3, which co-produces bla_(CTX-M-3), bla_(KPC-2), bla_(TEM-1B), qnrS1, aac(6')-Ib-cr, dfrA14, arr-3, and aac(6')-Ib3. Multiple genome arrangement analyses indicated that pEC258-3 is highly homologous with pCRKP-1-KPC discovered in Klebsiella pneumoniae from a patient. Furthermore, conjugation experiments proved that plasmid pEC258-3 can be transferred horizontally and may pose a significant potential threat in animals, community and hospital settings.
期刊：
CURRENT MEDICINAL CHEMISTRY,2023年 ISSN：0929-8673
作者机构：
[Liu, Yunmei; Zhang, Jiayao; Yang, Lingyan; Li, Hui; Shi, Lei; Liu, Zhenhua; Tian, Zejie] Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province 421001, China;[Liu, Yihui] The second Hospital, University of South China, Hengyang City, Hunan Province, 421001, China;[He, Jun] Institute of Chemistry & Chemical Engineering, University of South China, Hengyang City, Hunan Province, 421001, China
关键词：
Chemodynamic therapy(CDT);Nanomedicines;Photodynamic therapy(PDT);Porphyrins;ROS-mediated cancer treatments;Treatment for cancer
摘要：
High concentrations of reactive oxygen species (ROS) can disrupt cell structure and induce apoptosis and necrosis of tumor cells. Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are two cancer treatments mediated by reactive oxygen species. Oxygen molecules (O2 ) are one of the indispensable factors in PDT and hypoxic tumor sites limit its application. However, another ROS-mediated method, CDT, can generate •OH and O2 in situ by Fenton reaction or Fenton-like reaction. Synergistic PDT/CDT therapy is a strategy to overcome the limitations of tumor microenvironment therapy. In this review, PDT and CDT therapies are briefly introduced, with an emphasis on metal-basrd porphyrin nanoparticles constructed in different ways for PDT/CDT dual-mode therapy. By introducing the history and latest design schemes of the treatment model, it provides ideas for researchers engaged in ROS-mediated cancer therapies.
摘要：
Purpose: To investigate the effect of emodin on osteosarcoma cell proliferation and apoptosis.Methods: The osteosarcoma cell proliferation ability was determined by CCK-8, apoptosis level and cell cycle were determined via flow cytometry. Honechst staining was used to determine the ratio of nuclear pyknosis, Western blotting was used to determine the expression of AKT, p-AKT and caspase-3 precursor protein in each group of osteosarcoma cells.Results: Emodin significantly inhibited the MG-63 cell proliferation and promoted the apoptosis of osteosarcoma cells in a dose-dependent manner (p < 0.05). It further blocked osteosarcoma cells in G1/G0 phase and decreased the expression of AKT, p-AKT, and caspase-3 (p < 0.05).Conclusion: Emodin inhibits osteosarcoma cell growth by inhibiting ATM protein cleavage. There is a need to carry out further investigation of the effect of emodin on osteosarcoma cells using animal models in order to ascertain its potential in the management of osteosarcoma.
作者机构：
Department of Pharmacy, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China;Aiqun Liu and Baohong Jiang contributed equally to this work.;[Fu Peng] West China School of Pharmacy, Sichuan University, Chengdu, China;[Qizhi Zhong; Yufan Mo; Ruiqin Yang; Ciyu Chen] Department of Neurology, School of Clinical Medicine, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China;[Cailu Song; Hailin Tang] State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
通讯机构：
[Cheng Peng; Hailin Tang] S;[Fu Peng] W;West China School of Pharmacy, Sichuan University, Chengdu, China<&wdkj&>State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China<&wdkj&>State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
摘要：
Schematic of this study describing the roles and underlying mechanisms of isoliquiritigenin (ISL) on the circ0030018/miR‐1236/HER2 pathway in glioma progression. Circ0030018 was remarkably overexpressed in glioma and ISL could significantly downregulate circ0030018 expression, leading to dampened glioma growth and metastasis partially through the miR‐1236/HER2 signaling. Abstract In the central nervous system diseases, glioma is one of the most common malignancies around the world. Despite the recent improvements in therapies for glioma, the prognosis of some high‐risk glioma remains poor. In glioma, isoliquiritigenin (ISL) is reported to have antioxidative and antitumor activities. However, the potential mechanisms between ISL and circle RNAs (circRNAs) in the glioma tumorigenesis process have not yet been reported. Here, we treated glioma cells with ISL, and circRNA expression levels were detected. Circ0030018 was found significantly downregulated by ISL. Therefore, we explored circ0030018 expression profiles and functions in glioma, finding that circ0030018 was evidently overexpressed in glioma cell lines. Colony formation, CCK‐8, and transwell assay made clear that circ0030018 silencing dramatically cut down glioma growth and invasion. Moreover, ROS level was detected to find that circ0030018 silence remarkably enhanced cell oxidative stress in glioma. Mechanism studies were conducted to investigate the underlying basis of circ0030018 function in glioma, unveiling that circ0030018 realized its functions partially through the miR‐1236/HER2 signaling in glioma. In conclusion, our study investigated the roles and mechanisms of the ISL on the circ0030018/miR‐1236/HER2 pathway in glioma tumorigenesis and progression. Circ0030018 could act as the prospective biologic signature or therapeutic target for glioma.
摘要：
Long non-coding RNA (lncRNA) is a kind of biomolecule that can regulate important life activities such as cell proliferation, apoptosis, differentiation, aging, and body development. It has been found that lncRNAs are closely related to various diseases. In cardiovascular diseases, lncRNAs affect the expression level of related genes in atherosclerotic plaques, which are closely related to endothelial dysfunction, smooth muscle cell proliferation, macrophage dysfunction, abnormal lipid metabolism, and cellular autophagy, thus participating in regulating the occurrence and development of AS. In view of this, investigating the role of lncRNAs in regulating cardiac gene networks on cardiovascular system diseases has attracted much clinical attention and may be a novel target for AS therapy. This paper focuses on lncRNAs related to AS, explores the relationship between lncRNAs and AS, suggests the role of lncRNAs in the prevention and treatment of AS, and expects the application of more lncRNAs as the marker in the clinical diagnosis and treatment of AS.
摘要：
The endoplasmic reticulum (ER) is one of the most important organelles in cells, involved in protein synthesis, folding, and modification, as well as Ca2+ storage and release. ER homeostasis imbalances may contribute to various diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and cancer. Current research efforts primarily focus on ER-related disease mechanisms and drug candidate screening. Because disease processes involve multiple molecular events and signaling, an innovative tool is necessary to precisely detect key signaling molecules in the ER to accelerate the discovery of targeted therapeutics. In recent years, because of their real-time visualization, precise targeting, high sensitivity and specificity, low cytotoxicity, and synthetic tunability, fluorescent probes have been widely used to investigate biological processes and disease events. This review first introduces ER and its related biological processes, and the design rules of ER-targeted probes. Subsequently, based on the latest literature, it systematically summarizes the research progress of fluorescent probes for imaging physiological or pathological events in the ER. Lastly, it discusses the challenges of ER-targeted probes as well as the future development of probe engineering. We anticipate that this review will not only encourage the development of fluorescence probe engineering but will also enhance interdisciplinary research between chemistry, biology, pharmacology, and medicine, promoting for its widespread application.
通讯机构：
[Linxi Chen; Lanfang Li] I;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China
摘要：
Glycometabolism is well known for its roles as the main source of energy, which mainly includes three metabolic pathways: oxidative phosphorylation, glycolysis and pentose phosphate pathway. The orderly progress of glycometabolism is the basis for the maintenance of cardiovascular function. However, upon exposure to harmful stimuli, the intracellular glycometabolism changes or tends to shift toward another glycometabolism pathway more suitable for its own development and adaptation. This shift away from the normal glycometabolism is also known as glycometabolism reprogramming, which is commonly related to the occurrence and aggravation of cardiovascular diseases. In this review, we elucidate the physiological role of glycometabolism in the cardiovascular system and summarize the mechanisms by which glycometabolism drives cardiovascular diseases, including diabetes, cardiac hypertrophy, heart failure, atherosclerosis, and pulmonary hypertension. Collectively, directing GMR back to normal glycometabolism might provide a therapeutic strategy for the prevention and treatment of related cardiovascular diseases.
期刊：
Bioinorganic Chemistry and Applications,2023年2023 ISSN：1565-3633
通讯作者：
Li, R.;Feng, W.
作者机构：
[Song, Jingfang; Feng, Wei] Univ South China, Affiliated Hosp 2, Inst Pathogen Biol, Hengyang Med Sch,Dept Pediat, Hengyang 421001, Hunan, Peoples R China.;[Song, Jingfang; Feng, Wei; Li, Ranhui] Hunan Prov Key Lab Special Pathogens Prevent & Con, Hengyang 421001, Hunan, Peoples R China.;[Wang, Weiguo; Yang, Lin; He, Jian] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Bai, Qinqin] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Hunan, Peoples R China.;[Li, Ranhui] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Feng, W.] T;[Li, R.] I;Institute of Pathogenic Biology Hengyang Medical School University of South China, China;The Second Affiliated Hospital Department of Pediatrics Institute of Pathogenic Biology Hengyang Medical School University of South China, China
关键词：
Introduction;Materials and Methods;Results;Discussion;Conclusion;Abstract;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interests;Authors’ Contributions;Funding Statement;Acknowledgements;Acknowledgments;Supplementary Materials;Reference;Dataset Description;Dataset Files;Abstract;Introduction;Introduction and Materials;Introduction and Methods;Materials;Materials and Methods;Methods;Results;Discussion;Results and Discussion;Discussion and Conclusion;Results and Conclusion;Conclusion;Conclusions;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interest;Authors’ Contributions;Funding Statement;Acknowledgements;Supplementary Materials;References;Appendix;Abbreviations;Preliminaries;Introduction and Preliminaries;Notation;Proof of Theorem;Proofs;Analysis of Results;Examples;Numerical Example;Applications;Numerical Simulation;Model;Model Formulation;Systematic Palaeontology;Nomenclatural Acts;Taxonomic Implications;Experimental;Synthesis;Overview;Characterization;Background;Experimental;Theories;Calculations;Model Verification;Model Implementation;Geographic location;Study Area;Geological setting;Data Collection;Field Testing;Data and Sampling;Dataset;Literature Review;Related Works;Related Work;System Model;Methods and Data;Experimental Results;Results and Analysis;Evaluation;Implementation;Case Presentation;Case Report;Search Terms;Case Description;Case Series;Background;Limitations;Additional Points;Case;Case 1;Case 2 etc.;Concern Details;Retraction Details;Copyright;Related Articles
作者机构：
[Song, Zhiyin; Yu, Jianglong; He, He; Zhao, Huabin; Guo, Hanze; He, H; Gong, Longlong; Hao, Tianshu; Wu, Zhida; Wang, Bingjun; Jiang, Jie] Wuhan Univ, Renmin Hosp, Taikang Ctr life & Med Sci, Coll Life Sci,Frontier Sci Ctr Immunol & Metab,Dep, Wuhan 430072, Hubei, Peoples R China.;[Lu, Bin] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Engelender, Simone] Technion Israel Inst Technol, Rappaport Fac Med, Dept Biochem, Haifa, Israel.
通讯机构：
[He, H; Song, ZY ] W;Wuhan Univ, Renmin Hosp, Taikang Ctr life & Med Sci, Coll Life Sci,Frontier Sci Ctr Immunol & Metab,Dep, Wuhan 430072, Hubei, Peoples R China.
摘要：
Mitochondria are the key organelles for sensing oxygen, which is consumed by oxidative phosphorylation to generate ATP. Lysosomes contain hydrolytic enzymes that degrade misfolded proteins and damaged organelles to maintain cellular homeostasis. Mitochondria physically and functionally interact with lysosomes to regulate cellular metabolism. However, the mode and biological functions of mitochondria-lysosome communication remain largely unknown. Here, we show that hypoxia remodels normal tubular mitochondria into megamitochondria by inducing broad inter-mitochondria contacts and subsequent fusion. Importantly, under hypoxia, mitochondria-lysosome contacts are promoted, and certain lysosomes are engulfed by megamitochondria, in a process we term megamitochondria engulfing lysosome (MMEL). Both megamitochondria and mature lysosomes are required for MMEL. Moreover, the STX17-SNAP29-VAMP7 complex contributes to mitochondria-lysosome contacts and MMEL under hypoxia. Intriguingly, MMEL mediates a mode of mitochondrial degradation, which we termed mitochondrial self-digestion (MSD). Moreover, MSD increases mitochondrial ROS production. Our results reveal a mode of crosstalk between mitochondria and lysosomes and uncover an additional pathway for mitochondrial degradation. Several organelle membranes make contact in the cell, with many contacts being spatially segregated sites dedicated to specific functions. Here, Hao et al. show that hypoxia increases mitochondria-lysosome contacts, leading to engulfment and degradation of the mitochondria.
摘要：
BACKGROUND AND PURPOSE: Research has revealed the involvement of mitochondrial autophagy and iron death in the pathogenesis of myocardial fibrosis. The objective of this study is to investigate whether the mitochondrial-targeted H(2)S donor AP39 inhibits mitochondrial autophagy and antagonizes myocardial cell iron death through the PINK1/Parkin pathway, thereby improving myocardial fibrosis in rats with myocardial infarction. EXPERIMENTAL APPROACH: A rat model of myocardial infarction was created by intraperitoneal injection of a high dose of isoproterenol, and H9c2 myocardial cells were subjected to hypoxic injury induced by CoCl(2). Western blot, RT-PCR, transmission electron microscopy, immunohistochemistry, as well as echocardiography, and studies on isolated hearts were employed. KEY RESULTS: In the hearts of rats with myocardial infarction, there was a significant accumulation of interstitial collagen fibers, accompanied by downregulation of CSE protein expression, activation of the PINK1/Parkin signaling pathway, and activation of mitochondrial autophagy. Intervention with AP39 resulted in a significant improvement of the aforementioned changes, which could be reversed by the addition of PAG. Similar results were observed in vitro experiments. Furthermore, the addition of CCCP reversed the antagonistic effect of AP39 on myocardial cell iron death, while the addition of RSL3 reversed the inhibitory effect of AP39 on collagen production in myocardial cells. CONCLUSION AND IMPLICATIONS: The mitochondrial-targeted H(2)S donor AP39 can inhibit mitochondrial autophagy through the PINK1/Parkin pathway, antagonize myocardial cell iron death, and improve myocardial fibrosis in rats with myocardial infarction.
作者机构：
[Tang, Caihong; Jiang, Zhong-Xing; Yao, Xu; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Jianxin; Tang, Feng; Shi, Wei; Zeng, Yue; Tang, Caihong; Huang, Wei] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China.;[Shi, Wei; Huang, Wei] Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China.;[Huang, Wei] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China.;[Huang, Wei] Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
通讯机构：
[Xu Yao; Zhong-Xing Jiang] I;[Wei Shi; Wei Huang] C;CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zuchongzhi Road, Pudong, Shanghai 201203, China<&wdkj&>School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China<&wdkj&>School of Chinese Materia Medica, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing 210023, China<&wdkj&>University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China<&wdkj&>Shanghai GlycanLink Biotech. Co. Ltd., Minhang, Shanghai 201203, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hengyang Medicinal School, University of South China, Hengyang, Hunan 421001, China<&wdkj&>CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zuchongzhi Road, Pudong, Shanghai 201203, China<&wdkj&>School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China
摘要：
The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody–drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein–protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with the same payloads or with two types of payloads. The constructed dual-site ADCs showed acceptable homogeneity, excellent buffer stability, and enhanced in vitro and in vivo efficiency.
