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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings Marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

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World Journal of Methodology 2024年第2期14卷 65-74页

作者： Earl B Ettienne Emilio Russo Pasquale Striano Jane M Grant-Kels Klaus Rose College of Pharmacy Howard University College of PharmacyWashingtonDC 20059United States Department of Health Sciences School of MedicineRussoUniversity"Magna Graecia"of CatanzaroCatanzaro 88100Italy IRCCS Istituto Giannina Gaslini Genova 16148Italy Department of Dermatology University of Connecticut Health CenterFarmingtonCT 06032United States klausrose Consulting Pediatric Drug Development and moreMedical ScienceCH-4125 RiehenSwitzerland

Modern drugs have changed epilepsy,which affects people of all ***,for young people with epilepsy,the framework of drug development has *** the wake of the thalidomide catastrophe,the misconception emerged that for peopledrugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some *** now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another *** a result,some of the pediatric clinical epilepsy research over the past decades was *** more importantly,this has hampered research on meaningful research *** do not need to confirm that ASMs work before as they do after the 18th ***,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’*** we discuss how to proceed in this endeavor.

关键词： Epilepsy Pediatric drug development therapeutic orphans Antiseizure medications Pediatric investigation plan Clinical pharmacology

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Molecular classification of small cell lung cancer subtypes:Characteristics,prognostic factors,and clinical translation

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Chinese Medical Journal 2024年第2期137卷 130-139页

作者： Hanfei Guo Wenqian Li Ye Guo Naifei Chen Jiuwei Cui Cancer center The First Hospital of Jilin UniversityChangchunJilin 130021China

Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the *** recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC ***,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the ***,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.

关键词： Small cell lung carcinoma Molecular classification Tumor heterogeneity drug resistance Transcription factors Genomics Phenotype Prognosis

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A piezoelectric-driven microneedle platform for skin disease therapy

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The Innovation 2024年第3期5卷 110-121页

作者： Ziyan Chen Xin Liu Zixi Jiang Huayi Wu Tao Yang Lanyuan Peng Lisha Wu Zhongling Luo Mi Zhang Juan Su Yan Tang Jinmao Li Yang Xie Han Shan Qibo Lin Xiuli Wang Xiang Chen Hanmin Peng Shuang Zhao Zeyu Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008China Furong Laboratory(Precision Medicine) Changsha 410008China National Engineering Research center of Personalized Diagnostic and therapeutic Technology Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Engineering Research center of Skin Health and Disease Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research center of Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China School of Mechanical and Electrical Engineering Central South UniversityChangsha 410083China Department of Dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710000China State Key Laboratory of Mechanics and Control for Aerospace Structures Nanjing University of Aeronautics&AstronauticsNanjing 210016China Institute of Photomedicine Shanghai Skin Disease HospitalSchool of MedicineTongji UniversityShanghai 200443China

With over a million cases detected each year,skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate,propensity for recurrence,and potential for post-treatment *** therapy(PDT)is a treatment with minimal invasiveness or scarring and few side effects,making it well tolerated by ***,this treatment requires further research and development to improve its effective clinical ***,a piezoelectric-driven microneedle(PDMN)platform that achieves high efficiency,safety,and non-invasiveness for enhanced PDT is *** platform induces deep tissue cavitation,increasing the level of protoporphyrin IX and significantly enhancing drug penetration.A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT(PDMN-PDT).Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25%and 50%,respectively,without any anesthesia compared to traditional *** findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment,which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

关键词： needle anesthesia clinical

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The potential mechanism of Isodon suzhouensis against COVID-19 via EGFR/TLR4 pathways

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Food Science and Human Wellness 2024年

作者： Hong Duan Wei Wang Shu Li Han Li Ghulam Jilany Khan Fawang Liu Kefeng Zhai Lili Li Zhaojun Wei General Clinical Research center Anhui Wanbei Coal-Electricity Group General Hospital Department of Pharmacology and therapeutics Faculty of Pharmacy University of Central Punjab College of Biological and Food Engineering Anhui Polytechnic University School of Biological and Food Engineering Engineering Research center for development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province Suzhou University School of Food and Biological Engineering Hefei University of Technology

Corona Virus Disease 2019 (COVID-19) has brought the new challenges to scientific research. Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects， which is considered as a potential treatment for COVID-19. The possibility for the treatment of COVID-19 with suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology. Network pharmacology and molecular docking were used to screen drug targets， and Lipopolysaccharide (LPS) induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification. Collectively a total of 209 possible linkages against 18 chemical components from suzhouensis and 1194 COVID-19 related targets were selected. Among these， 164 common targets were obtained from the intersection of suzhouensis and COVID-19. GO and KEGG enriched 582 function targets and 87 target proteins pathways， respectively. The results from molecular docking studies revealed that rutin， vitexin， isoquercitrin and quercetin had significant binding ability with SARS-CoV-23CLpro and ACE2. In vitro studies showed that Isodon suzhouensis extract (ISE) may inhibit the activation of PI3K/Akt pathway and the expression level of downstream pro-inflammatory factors by inhibiting the activation of EGFR in RAW264.7 cells induced by LPS. In addition， ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS. Overall， the network pharmacology and in vitro studies conclude that active components from suzhouensis have strong therapeutic potential against COVID-19 through multi-target， multi-pathway dimensions and can be a promising candidate against COVID-19.

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The significance of long non-coding RNAs in the pathogenesis,diagnosis and treatment of inflammatory bowel disease

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Precision Clinical Medicine 2024年第1期7卷 34-53页

作者： Fei Jiang Min Wu Rongpeng Li Jiangsu Province Engineering Research center of Cardiovascular drugs Targeting Endothelial Cells School of Life SciencesJiangsu Normal UniversityXuzhou 221000China Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000China drug Discovery Section Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China Department of Neurology Medical College of WisconsinMilwaukeeWI 53226USA

Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global *** the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain *** non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding *** play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional *** this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.

关键词： lncRNAs inflammatory bowel diseases intestinal barrier intestinal microenvironment immune regulator diagnostic biomarker therapeutic target

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Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 795-807页

作者： Yongchun Pan Xiaowei Luan Fei Zeng Xuyuan Wang Shurong Qin Qianglan Lu Guanzhong He Yanfeng Gao Xiaolian Sun Xin Han Bangshun He Yujun Song Department of Laboratory Medicine Nanjing First HospitalNanjing Medical UniversityNanjing 210006China College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjing 210023China State Key Laboratory of Natural Medicines Key Laboratory of Drug Quality Control and PharmacovigilanceDepartment of Pharmaceutical AnalysisChina Pharmaceutical UniversityNanjing 211198China School of Medicine&Holistic Integrative Medicine Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationNanjing University of Chinese MedicineNanjing 210023China

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene ***,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor ***,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer *** this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are *** intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as *** the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target *** tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation ***,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

关键词： CRISPRdelivery Enzymeencapsulation Logic gate Hybridmaterial Hypoxia Gene editing Precise nanomedicine Multimodal therapy

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Chronic stress as an emerging risk factor for the development and progression of glioma

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Chinese Medical Journal 2024年第4期137卷 394-407页

作者： Lan Yi Xiang Lin Xiaoling She Wei Gao Minghua Wu Institute of Cytology and Genetics The Hengyang Key Laboratory of Cellular Stress BiologyHunan Province Cooperative Innovation Center for Molecular Target New Drug StudyHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Department of Pathology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education Cancer Research InstituteCentral South UniversityChangshaHunan 410008China NHC Key Laboratory of Carcinogenesis Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous *** with patients with other cancers,glioma patients often suffer from increased levels of psychological stress,such as anxiety and *** stress(CS)is thought to impact glioma ***,because of the complex mechanisms underlying CS and variability in individual tolerance,the role of CS in glioma remains *** review suggests a new proposal to redivide the stress system into two *** activity is dominant ***-signaling molecules produced by the neuroendocrine system are dominant *** discuss the underlying molecular mechanisms by which CS impacts *** pharmacological treatments are also summarized from the therapeutic perspective of CS.

关键词： Chronic stress Glioma Microbiota-gut-brain axis Neuroendocrine system Stress system Neural circuit

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on drug Dependence and Beijing Key Laboratory of drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway

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Science China(Life Sciences) 2023年第12期66卷 2805-2817页

作者： Guanglei Chen Lisha Sun Xi Gu Liping Ai Jie Yang Zhan Zhang Pengjie Hou Yining Wang Xunyan Ou Xiaofan Jiang Xinbo Qiao Qingtian Ma Nan Niu Jinqi Xue Hao Zhang Yongliang Yang Caigang Liu Department of Oncology Cancer Stem Cell and Translation Medicine LabInnovative Cancer Drug Research and Development Engineering Center of Liaoning ProvinceShengjing Hospital of China Medical UniversityShenyang 110004China School of Bioengineering Dalian University of TechnologyDalian 116024China

CDK4/6 inhibitors are routinely recommended agents for the treatment of advanced HR+HER2-breast ***,their therapeutic effectiveness in triple-negative breast cancer(TNBC)remains ***,we observed that the expression level of fibrous sheath interacting protein 1(FSIP1)could predict the treatment response of TNBC to CDK4/6 *** FSIP1 expression level was related to a poor prognosis in TNBC,which was associated with the ability of FSIP1 to promote tumor cell ***1 downregulation led to slowed tumor growth and reduced lung metastasis in ***1knockout caused cell cycle arrest at the G0/G1 phase and reduced treatment sensitivity to CDK4/6 inhibitors by inactivating the Nanog/CCND1/CDK4/6 ***1 could form a complex with Nanog,protecting it from ubiquitination and degradation,which may facilitate the rapid cell cycle transition from G0/G1 to S phase and exhibit enhanced sensitivity to CDK4/6 *** findings suggest that TNBC patients with high FSIP1 expression levels may be suitable candidates for CDK4/6 inhibitor treatment.

关键词： FSIP1 CDK4/6 inhibitors triple-negative breast cancer

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