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Chinese Journal of Natural Medicines 2022年第4期20卷 290-300页

作者： DU Bing-Xin LIN Pei LIN Jun School of Life Sciences and Health Engineering Jiangnan UniversityWuxi 214122China

Catechins have been proven to exert antitumor effects in different kinds of cancers.However,the underlying mechanisms have not been completely clarified yet.This study aimed to assess the effects and mechanisms of(-)-epigallocatechin-3-gallate(EGCG)and(-)-epicatechin-3-gallate(ECG)on human melanoma skin A375 cells.Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect.Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest.EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level,indicating the development of apoptosis.Furthermore,EGCG and ECG could decreased mitochondrial membrane potential of A375 cells.In addition,the expression of Beclin-1,LC3 and Sirt3 were downregulated at protein levels,which known to be associated with autophagy.After autophagy was increased by rapamycin,the apoptotic trend was not change,indicating that apoptosis and autophagy are independent.Mechanistically,EGCG and ECG treatments decreased phosphorylated-AMPK(p-AMPK)and increased the ratios of P-PI3K,p-AKT and p-mTOR in melanoma cells.Conclusively,EGCG and ECG induced apoptosis via mitochondrial signaling pathway,downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway.It indicated that EGCG and ECG may be utilized in human melanoma treatment.

关键词： EGCG ECG Apoptosis Autophagy PI3K/AKT/mTOR

Five Rutaceae family ethanol extracts alleviate H2O2 and LPS-induced inflammation via NF-κB and JAK-STAT3 pathway in HaCaT cells

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Chinese Journal of Natural Medicines 2022年第12期20卷 937-947页

作者： HONG Mengsa XIAO Kun LIN Pei LIN Jun School of Life Sciences and Health Engineering Jiangnan UniversityWuxi 214122China

This study was designed to investigate the effects of five Rutaceae family ethanol extracts(FRFEE):Citrus medica Linn(CML),Citrus aurantium L.Cv.Daidai(CAD),Citrus medica Linn.***.sarcodactylis(Noot.)Swingle(CMS),Citrus sinensis L.Osbeck(CSO)and Zanthoxylum bungeanum Maxim(ZBM)on retarding the progression of H_(2)O_(2) and LPS-induced HaCaT cells.Cell inflammatory injury model was established by H_(2)O_(2) and LPS.The alleviative effects of FRFEE were evaluated by detecting the activity of superoxide dismutase(SOD),glutathione(GSH)and the generation of reactive oxygen species(ROS).The inflammatory signaling pathways of NF-κB and JAK-STAT3 were detected by Western blotting,the mRNA expression levels of inflammatory factors and skin barrier factors were detected by RT-PCR.50%ethanol extracts of five medicinal and food homologous herbs of Rutaceae family showed different levels of anti-oxidant and anti-inflammatory activities.The FRFEE effectively improved SOD and GSH content and decreased ROS levels.Meanwhile,FRFEE strongly suppressed two inflammatory signaling pathways NF-κB and JAK-STAT3.The RT-PCR examination of inflammatory factors and skin barrier factor revealed significant anti-inflammatory effects of FRFEE.It was worth noting that among the five extracts,Zanthoxylum bungeanum Maxim extract had the best anti-inflammatory and anti-oxidation effects.In addition,it could strongly inhibit the expression of psoriasis factor CCL20.In summary,these results suggested that Zanthoxylum bungeanum Maxim extract could be used as an anti-psoriatic agent in the treatment of psoriasis among FRFEE.

关键词： Rutaceae Medicinal and food homologous herbs Oxidative stress Anti-inflammation Psoriasis

A benchtop brain injury model using resected donor tissue from patients with Chiari malformation

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Neural Regeneration Research 2023年第5期18卷 1057-1061页

作者： Jacqueline A.Tickle Jon Sen Christopher Adams David N.Furness Rupert Price Viswapathi Kandula Nikolaos Tzerakis Divya M.Chari Aston Pharmacy school College of Health and Life SciencesAston UniversityBirminghamUK school of Medicine Faculty of Medicine and Health SciencesKeele UniversityStaffordshireUK school of life sciences Keele UniversityStaffordshireUK Department of Neurosurgery Royal Stoke University HospitalStoke-on-TrentUK

The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3 D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation(cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.

关键词： biomaterial Chiari malformation cerebellar slice human tissue injury model neuroregeneration organotypic traumatic brain injury

Drug Repurposing for the Treatment of Mycobacterium abscessus Infections

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感染微生物与疾病(英文) 2023年第3期5卷 101-110页

作者： Emily J.Baker Antonia Molloy Jonathan A.G.Cox school of life and health sciences Aston UniversityAston TriangleBirminghamUK.

With the ever-increasing burden of antimicrobial resistance,the demand to introduce countermeasures becomes increasingly critical.The urgency of this need is intensified by the void in antibiotic discovery,with the identification of novel compounds declining with time.Of increasing concern is Mycobacterium abscessus,which displays high levels of intrinsic resistance that lead to poor success rates,even after lengthy drug regimens.Research tackling these issues is now focused on the repurposing of preexisting drugs for antimycobacterial use,facilitating the discovery of antimicrobial compounds amidst a crisis where novel antibiotics are sparse.Part of this includes the use of combination treatments,whereby coadministration of synergistic compounds can reduce dose requirements and slow the progression of antimicrobial resistance in the long term.In this review,we will introduce the current therapeutic options for M.abscessus and provide insight into why treatment is so burdensome.We will also compile the current updates within drug repurposing for this pathogen,including the use of unconventional agents such as antimalarial drugs,the repositioning of antitubercu-losis candidates and the repurposing of preexisting antibiotics,including the application of combination regimens.In addition,the in vitro drug screening platforms used in their discovery will be appraised,with the view of highlighting potential future perspectives that may help increase physiological relevance.This review provides a timely appraisal of the future of M.abscessus treatment.

关键词： drug repurposing Mycobacterium abscessus antimycobacterial drug discovery antimicrobials

N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies

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Virologica Sinica 2015年第6期30卷 449-456页

作者： Dezhi Li Jie Liu Li Zhang Tianshu Xu Junheng Chen Liping Wang Qi Zhao school of life sciences Xiamen University Laboratory of Fully Human Antibody engineering Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences school of life sciences Jilin University Faculty of health sciences University of Macao

The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.

关键词： HIV-1 membrane proximal external region(MPER) 2F5 neutralizing antibody yeast display

KinasePhos 3.0:Redesign and Expansion of the Prediction on Kinase-specific Phosphorylation Sites

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 228-241页

作者： Renfei Ma Shangfu Li Wenshuo Li Lantian Yao Hsien-Da Huang Tzong-Yi Lee Warshel Institute for Computational Biology School of MedicineThe Chinese University of Hong KongShenzhen 518172China school of life sciences University of Science and Technology of ChinaHefei 230027China school of Science and engineering The Chinese University of Hong KongShenzhen 518172China school of life and health sciences School of MedicineThe Chinese University of Hong KongShenzhen 518172China

The purpose of this work is to enhance KinasePhos,a machine learning-based kinasespecific phosphorylation site prediction tool.Experimentally verified kinase-specific phosphorylation data were collected from PhosphoSitePlus,UniProtKB,the GPS 5.0,and Phospho.ELM.In total,41,421 experimentally verified kinase-specific phosphorylation sites were identified.A total of 1380 unique kinases were identified,including 753 with existing classification information from KinBase and the remaining 627 annotated by building a phylogenetic tree.Based on this kinase classification,a total of 771 predictive models were built at the individual,family,and group levels,using at least 15 experimentally verified substrate sites in positive training datasets.The improved models demonstrated their effectiveness compared with other prediction tools.For example,the prediction of sites phosphorylated by the protein kinase B,casein kinase 2,and protein kinase A families had accuracies of 94.5%,92.5%,and 90.0%,respectively.The average prediction accuracy for all 771 models was 87.2%.For enhancing interpretability,the SHapley Additive exPlanations(SHAP)method was employed to assess feature importance.The web interface of KinasePhos 3.0 has been redesigned to provide comprehensive annotations of kinase-specific phosphorylation sites on multiple proteins.Additionally,considering the large scale of phosphoproteomic data,a downloadable prediction tool is available at https://***/KinasePhos/download.html or https://***/tom-209/KinasePhos-3.0-executable-file.

关键词： Kinase-specific phosphorylation Phosphorylation site prediction Phosphorylation SHAP feature importance Kinase

Current state and future perspectives of cytochrome P450 enzymes for C-H and C=C oxygenation

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Synthetic and Systems Biotechnology 2022年第3期7卷 887-899页

作者： Yu Yan Jing Wu Guipeng Hu Cong Gao Liang Guo Xiulai Chen Liming Liu Wei Song State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi214122China School of Life Sciences and Health Engineering Jiangnan UniversityWuxi214122China

Cytochrome P450 enzymes(CYPs)catalyze a series of C-H and C=C oxygenation reactions,including hydroxylation,epoxidation,and ketonization.They are attractive biocatalysts because of their ability to selectively introduce oxygen into inert molecules under mild conditions.This review provides a comprehensive overview of the C-H and C=C oxygenation reactions catalyzed by CYPs and the various strategies for achieving higher selectivity and enzymatic activity.Furthermore,we discuss the application of C-H and C=C oxygenation catalyzed by CYPs to obtain the desired chemicals or pharmaceutical intermediates in practical production.The rapid development of protein engineering for CYPs provides excellent biocatalysts for selective C-H and C=C oxygenation reactions,thereby promoting the development of environmentally friendly and sustainable production processes.

关键词： Biocatalysis P450 enzymes C-H and C=C oxygenation

An integrated genome-wide analysis identifies HUR/ELAVL1 as a positive regulator of osteogenesis through enhancing theβ-catenin signaling activity

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Genes & Diseases 2023年第2期10卷 377-380页

作者： Ying Huai Zhihao Chen Xiaoni Deng Xue Wang Wenjing Mao Zhiping Miao Yu Li Hui Li Xiao Lin Airong Qian Lab for Bone Metabolism Xi'an Key Laboratory of Special Medicine and Health EngineeringSchool of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Key Lab for Space Biosciences and Biotechnology School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Research Center for Special Medicine and health Systems engineering School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China NPU-UAB Joint Laboratory for Bone Metabolism School of Life SciencesNorthwestern Polytechnical UniversityXi'anShaanxi 710072China Honghui Hospital Xi'an Jiaotong University College of MedicineXi'anShaanxi 710054China

Osteoporosis is a prevalent multifactorial bone disease with a strong genetic contribution.The heritability of traits that contribute to osteoporosis(bone mass,bone mineral density(BMD),bone size,bone loss and fractures)ranges from 50 to 85%,suggesting that a comprehensive understanding of the genetic basis may help identify new therapeutic targets.1 However,the genetic characteristics remain obscure,and the existing drug targets are associated with various challenges.Numerous studies have demonstrated that high-throughput sequencing data analysis is fruitful for identifying novel targets of human diseases.2 We therefore integrated GWAS and transcriptome analyses through Multi-marker Analysis of GenoMic Annotation(MAGMA)and weighted gene co-expression network analysis3(WGCNA)to identify new network modules and potential therapeutic genes for osteoporosis.As an illustration,the flow chart presenting the process of the present study was shown in Figure S1.

关键词： osteoporosis analysis Figure

Was Wuhan the early epicenter of the COVID-19 pandemic?——a critique

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National Science Review 2023年第4期10卷 19-21页

作者： Yanan Cao Lingling Chen Hua Chen Yupeng Cun Xiaofeng Dai Hongli Du Feng Gao Fengbiao Guo Yalong Guo Pei Hao Shunmin He Shunping He XiongLei He Zheng Hu Boon-Peng Hoh Xin Jin Qian Jiang Qinghua Jiang Asifullah Khan Hong-Zhi Kong Jinchen Li Shuai Cheng Li Ying Li Qiang Lin Jianquan Liu Qi Liu Jian Lu Xuemei Lu Shujin Luo Qinghua Nie Zilong Qiu Tieliu Shi Xiaofeng Song Jianzhong Su Sheng-ce Tao Chaolong Wang Chuan-Chao Wang Guo-Dong Wang Jiguang Wang Qi Wu Shaoyuan Wu Shuhua Xu Yu Xue Wenjun Yang Zhaohui Yang Kai Ye Yuan-Nong Ye Li Yu Fangqing Zhao Yiqiang Zhao Weiwei Zhai Dandan Zhang Liye Zhang Houfeng Zheng Qi Zhou Tianqi Zhu Ya-ping Zhang Institut Pasteur of Shanghai Chinese Academy of Sciences Institute of Biophysics Chinese Academy of Sciences Institute of Hydrobiology Chinese Academy of Sciences school of life sciences Sun Yat-sen University Institute of Synthetic Biology Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences Faculty of Medicine and health sciences University College Sedaya International school of Medicine South China University of Technology Department of Medical Genetics Capital Institute of Pediatrics school of life Science and Technology Harbin Institute of Technology Department of Biochemistry Abdul Wali Khan University Ruijin Hospital Shanghai Jiao Tong University Xiangya Hospital Central South University Department of Computer Science City University of Hong Kong College of life Science and Technology Foshan University South China Sea Institute of Oceanology Chinese Academy of Sciences College of Ecology Lanzhou University school of life sciences and Technology Tongji University school of life sciences Peking University Kunming Institute of Zoology Chinese Academy of Sciences College of Animal Science South China Agricultural University Institute of Neuroscience Chinese Academy of Sciences College of life Science and Technology Guangxi University school of life sciences East China Normal University Nanjing University of Aeronautics and Astronautics Wenzhou Institute University of Chinese Academy of Sciences Institute of Systems Biomedicine Shanghai Jiao Tong University Tongji Medical College Huazhong University of Science and Technology school of life sciences Xiamen University Division of life Science and Department of Chemical and Biological engineering The Hong Kong University of Science and Technology Institute of Microbiology Chinese Academy of Sciences school of life sciences Jiangsu Normal University school of life sciences Fudan University Beijing Institute of Genomics Chinese Academy of Sciences College of life Science and Technology Huazhong University of Science and Technology International Cen

Recently, Worobey et al.(2022) published a report entitled ‘The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic’ that succinctly summarizes their study [1]. A pre-print version of this study had earlier elicited a series of highprofile media coverages [2,3]. All these reports deliver a social-political message that the Huanan market is the epicenter of COVID-19.

关键词： SARS-COV-2 ORIGIN

Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds

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Bioactive Materials 2022年第3期7卷 358-372页

作者： Chia-Chen Hsu Julian H.George Sharlayne Waller Cyril Besnard David A Nagel Eric J Hill Michael D.Coleman Alexander M.Korsunsky Zhanfeng Cui Hua Ye Institute of Biomedical engineering Department of Engineering ScienceUniversity of OxfordOX37DQUK MBLEM Department of Engineering ScienceUniversity of OxfordParks RoadOxfordOX13PJUK school of Biosciences College of Health and Life SciencesAston UniversityBirminghamB47ETUK Translational Medicine Research Group Aston Medical SchoolCollege of Health and Life SciencesAston UniversityBirminghamB47ETUK

To reflect human development,it is critical to create a substrate that can support long-term cell survival,differentiation,and maturation.Hydrogels are promising materials for 3D cultures.However,a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction.Herein,granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell(hiPSC)-derived neural networks.A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules.Cells and hydrogel granules were combined using a weaker secondary gelation step,forming self-supporting cell laden scaffolds.At three and seven days,granular scaffolds supported higher cell viability compared to bulk hydrogels,whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions(65.52±11.59μm)after seven days compared to bulk hydrogels(22.90±4.70μm).Long-term(three-month)cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold.This approach is significant as it provides a simple,rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

关键词： Microgel Hydrogel Hyaluronan iPSC Neural tissue engineering 3D printing