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Dual-targeted lung cancer therapy via inhalation delivery of UCNP-siRNA-AS1411 nanocages

Cancer Biology & Medicine 2022年第7期19卷 1047-1060页

作者： Yu Han Yuming Yang Qiuyang Sun Bin Li Caixia Yue Yanlei Liu Jesús M.de la.fuente Daxiang Cui Institute of Nano Biomedicine and Engineering Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of EducationShanghai Engineering Research Center for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science&EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China National Engineering Center for Nanotechnology Collaborative Innovational Center for System BiologyShanghai 200241China department of Neurosurgery Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China Instituto de Nanociencia de Aragon(INA) Universidad de ZaragozaZaragoza 50018Spain

Objective:Although great progress has been made in the field of siRNA gene therapy,safe,efficient,and targeted delivery of siRNA are still major challenges in siRNA ***:We developed an up-conversion nanoparticle-based nanocage *** system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites,due to modifications of targeted molecules on the surfaces of nanocages and local ***:The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites,where they *** with the passive target and control groups,the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of ***:The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor *** with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes,high tumor inhibition ratios,and longer survival times.

关键词： Nanomaterials VEGF siRNA lung cancer gene therapy siRNA delivery

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Por los poros de la vida

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今日中国（西班牙文版） 2024年第7期 33页

作者： DAVlD fuente

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Management of lung cancer in the COVID-19 pandemic:a review

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 145-157页

作者： Fernando Maroto Piñeiro Carmen Trinidad López Javier de la.fuente Aguado department of Internal Medicine Hospital Povisa Ribera Salud Salamanca 5 Vigo 36211Spain Radiology Service Hospital Povisa Ribera Salud Salamanca 5 Vigo 36211Spain.

Since its inception,the COVID-19 pandemic has affected health care as a *** patients in general and those suffering from lung cancer in particular are a vulnerable group because of their many intrinsic characteristics and care *** SARS-CoV-2(COVID-19)infection affects these patients regarding their risk of infection and outcome in this patient cohort is still to be *** this review,we tried to summarize our main concerns regarding COVID-19 in the context of cancer patients from a clinical and multidisciplinary *** types of lung cancer treatments(chemotherapy,radiation therapy and immunotherapy)may also influence the risk of infection and condition the patient´s risk of having a worse *** cancer patients require frequent radiologic study follow-ups,which may be affected by COVID-19 ***-19 related incidental radiologic findings can appear in routinely scheduled radiology tests,which may be difficult to *** cancer treatment induced pneumonitis may have similar radiologic features similar to those in acute SARS-CoV-2 pneumonia and lead to a wrong *** different health care needs,the requirement for continuous health care access and follow-ups,and the clinical traials in which this patient population might be enrrolled are all being affected by the current COVID-19 health *** COVID-19 pandemic has put health care providers and institutions in difficult situations and obliged them to face challenging ethical *** issues,in turn,have also affected the psychological well-being of health care workers.

关键词： COVID-19 cancer ethics CT thorax lung cancer cancer treatment chemotherapy immunotherapy

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Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

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World Journal of Hepatology 2019年第1期11卷 50-63页

作者： Maria J Citores Jose L Lucena Sara de la.fuente Valentin Cuervas-Mons department of Internal Medicine Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana Liver Transplantation Unit Hospital Universitario Puerta de Hierro-Majadahonda department of Surgery Hospital Universitario Puerta de Hierro-Majadahonda Valentin Cuervas-Mons Department of Internal Medicine HospitalUniversitario Puerta de Hierro-Majadahonda department of Medicine Universidad Autónoma de Madrid

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after *** biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after *** transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed t

关键词： Hepatocellular carcinoma Liver transplantation Recurrence Selection criteria Prognostic score Biomarker Alpha-fetoprotein Systemic inflammatory marker

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Umbilical cord as a mesenchymal stem cell source for treating joint pathologies

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World Journal of Orthopedics 2011年第6期2卷 43-50页

作者： María Carmen Arufe Alexandre de la.fuente Isaac fuentes Francisco Javier de Toro Francisco Javier Blanco department of Medicine Area of Anatomy and Human EmbryologyCampus Oza s/nFac.of Health ScienceUniversity of A Coruna15006 A CorunaSpain Osteoarticular and Aging Research lab Cellular Therapy UnitINIBIC-CH Universitario A Coruna15006 A CorunaSpain Rheumatology Division INIBIC-CH Universitario A Coruna15006 A CorunaSpain Cathedra Bioiberica Universidad de A Coruna15006 A CorunaSpain CIBER-BBN-Instituto de Salud Carlos III 15006 A CorunaSpain Centro de Investigacion Biomedica Hospital Universitario A CorunaC/Xubias 8415006 A CorunaSpain

Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of ***,the regeneration of articular cartilage is a continuing challenge for biomedical *** of the most promising therapeutic approaches is cellbased tissue engineering,which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured *** use of healthy chondrocytes has been found to have limitations.A promising alternative cell population is mesenchymal stem cells(MSCs),known to possess excellent proliferation potential and proven capability for differentiation into ***“immunosuppressive”property of human MSCs makes them an important candidate for allogeneic cell *** use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting *** allogeneic cell-based approach would enable MSCs to be isolated from any donor,expanded and cryopreserved in allogeneic MSC banks,providing a readily available source of progenitors for cell replacement *** possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology *** objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.

关键词： Human Mesenchymal stem cell Umbilical cord Cartilage degeneration

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Artificial intelligence in theranostics of gastric cancer, a review

Medical Review

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Medical Review 2023年第3期3卷 214-229页

作者： Yiqian Zha Cuili Xue Yanlei Liu Jian Ni Jesus M.de la.fuente Daxiang Cui Institute of Nano Biomedicine and Engineering Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment InstrumentSchool of Sensing Science and EngineeringShanghai Jiao Tong UniversityShanghaiChina National Engineering Research Center for Nanotechnology ShanghaiChina Institute of Aragon Nanoscience University of ZaragozaZaragozaSpain

Gastric cancer (GC) is one of the commonestcancers with high morbidity and mortality in the *** to realize precise diagnosis and therapy of GC ownsgreat clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to earlydiagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in earlyscreening, diagnosis, therapy and prognosis of stomachcarcinoma. Especially AI combined with breath screeningearly GC system improved 97.4 % of early GC diagnosisratio, AI model on stomach cancer diagnosis system of salivabiomarkers obtained an overall accuracy of 97.18 %, speci-ficity of 97.44 %, and sensitivity of 96.88 %. We also discussconcept, issues, approaches and challenges of AI applied instomach cancer. This review provides a comprehensive viewand roadmap for readers working in this field, with the aimof pushing application of AI in theranostics of stomachcancer to increase the early discovery ratio and curativeratio of GC patients.

关键词： artificial intelligence diagnosis gastric cancer prognosis screening therapy

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Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer

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Nano-Micro Letters 2020年第10期12卷 36-52页

作者： Yanlei Liu Jingxing Yang Bin Liu Wen Cao Jingpu Zhang Yuming Yang Lijun Ma Jesus Martinez de la.fuente Jie Song Jian Ni Chunfu Zhang Daxiang Cui Institute of Nano Biomedicine and Engineering Key Laboratory for Thin Film and Microfabrication of Ministration of EducationShanghai Engineering Research Centre for Intelligent Diagnosis and Treatment InstrumentDepartment of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong University800 Dongchuan RoadShanghai 200240People’s Republic of China National Engineering Center for Nanotechnology Shanghai 200240People’s Republic of China department of Nuclear Medicine Rui Jin HospitalSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Scientific Research Center Shanghai Public Health Clinical CenterFudan UniversityShanghai 201508People’s Republic of China Tongren Hospital Shanghai Jiao Tong University School of Medicine1111 XianXia RoadShanghai 200336People’s Republic of China

How to trigger strong anti-tumor immune responses has become a focus for tumor ***,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy(PDT)and enhanced ***6 photosensitizer was attached on manganese dioxide(MnO2)nanoparticles,and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 *** iPS-MnO2@Ce6 actively targeted in vivo tumors,the acidic microenvironment triggered interaction between MnO2 and H2O2,released large quantities of oxygen,alleviated hypoxia in *** PDT,singlet oxygen formed,broken iPSs released tumor-shared antigens,which evoked an intensive innate and adaptive immune response against the tumor,improving dendritic cells matured,effector T cells,and natural killer cells were ***,regulatory T cells were reduced,and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6(Pdels with *** iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.

关键词： Human iPS MnO2@Ce6 nanoprobes Photodynamic therapy Immunotherapy Cancer

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Significance of the balance between intracellular glutathione and polyethylene glycol for successful release of small interfering RNA from gold nanoparticles

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Nano Research 2015年第10期8卷 3281-3292页

作者： Mark McCully Yulan Hernandez Joao Conde Pedro V. Baptista Jesus M. de la.fuente Andrew Hursthouse David Stirling Catherine C. Berry CentreforCellEngineering UniversityofGlasgowGlasgowG128QQScotlandUK InstituteofNanoscienceofAragon UniversityofZaragozaZaragoza50018Spain MassachusettsInstituteofTechnology InstituteforMedicalEngineeringandScienceHarvard-MITDivisionforHealthSciencesandTechnologyCambridgeMassachusetts02139USA UCIBIO DepartamentodeCienciasdaVidaFaculdadedeCienciaseTecnologiaUniversidadeNovadeLisboaCampusdeCaparicaCaparica2829-516Portugal InstitutodeCienciadeMaterialesdeAragon(ICMA) CSIC-UniversidaddeZaragozac/PedroCerbuna12Zaragoza50009Spain InstituteofNanoBiomedicineandengineering KeyLaboratoryforThinFilmandMicrofabricationTechnologyoftheMinistryofEducationResearchInstituteofTranslationMedicineShanghaiJiaoTongUniversityDongchuanRoad800Shanghai200240China SchoolofScience UniversityoftheWestofScotlandPaisleyPA12BEScotlandUK

The therapeutic promise of small interfering RNAs （siRNAs） for specific gene silencing is dependent on the successful delivery of functional siRNAs to the cytoplasm. Their conjugation to an established delivery platform, such as gold nanoparticles, offers tremendous potential for treating diseases and advancing our understanding of cellular processes. Their success or failure is dependent on both the uptake of the nanoparticles into the cells and subsequent intracellular release of the functional siRNA. In this study, utilizing gold nanoparticle siRNA-mediated delivery against C-MYC, we aimed to determine if we could achieve knockdown in a cancer cell line with low levels of intracellular glutathione, and determine the influence, if any, of polyethylene glycol （PEG） ligand density on knockdown, with a view to determining the optimal nanoparticle design to achieve C-MYC knockdown. We demonstrate that, regardless of the PEG density, knockdown in cells with relatively low glutathione levels can be achieved, as well as the possible effect of steric hindrance of PEG on the availability of the siRNA for cleavage in the intracellular environment. Gold nanoparticle uptake was demonstrated via transmission electron microscopy and mass spectroscopy, while knockdown was determined at the protein and physiological levels （cells in S-phase） by in-cell westerns and BrdU incorporation, respectively.

关键词： gold nanoparticles PEG glutathione siRNA drug delivery

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Binary Fruit Fly Swarm Algorithms for the Set Covering Problem

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Computers, Materials & Continua 2022年第6期71卷 4295-4318页

作者： Broderick Crawford Ricardo Soto Hanns de la.fuente Mella Claudio Elortegui Wenceslao Palma Claudio Torres-Rojas Claudia Vasconcellos-Gaete Marcelo Becerra Javier Pena Sanjay Misra Pontificia Universidad Católica de Valparaíso Valparaíso2362807Chile LERIA Universitéd’AngersAngers49000France department of Computer Science and Communication Ostfold University CollegeHaldenNorway

Currently,the industry is experiencing an exponential increase in dealing with binary-based combinatorial *** this sense,metaheuristics have been a common trend in the field in order to design approaches to solve them ***,a well-known strategy consists in the use of algorithms based on discrete swarms transformed to perform in binary *** the No Free Lunch theorem,we are interested in testing the performance of the Fruit Fly Algorithm,this is a bio-inspired metaheuristic for deducing global optimization in continuous spaces,based on the foraging behavior of the fruit fly,which usually has much better sensory perception of smell and vision than any other *** the other hand,the Set Coverage Problem is a well-known NP-hard problem with many practical applications,including production line balancing,utility installation,and crew scheduling in railroad and mass transit *** this paper,we propose different binarization methods for the Fruit Fly Algorithm,using Sshaped and V-shaped transfer functions and various discretization methods to make the algorithm work in a binary search *** are motivated with this approach,because in this way we can deliver to future researchers interested in this area,a way to be able to work with continuous metaheuristics in binary *** new approach was tested on benchmark instances of the Set Coverage Problem and the computational results show that the proposed algorithm is robust enough to produce good results with low computational cost.

关键词： Set covering problem fruit fly swarm algorithm metaheuristics binarization methods combinatorial optimization problem

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Gene expression changes in spleens of the wildlife reservoir species,Eurasian wild boar(Sus scrofa),naturally infected with Brucella suis biovar 2

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Journal of Genetics and Genomics 2010年第11期37卷 725-736页

作者： Ruth C.Galindo Pilar M.Muoz María J.de Miguel Clara M.Marin Javier labairu Miguel Revilla José M.Blasco Christian Gortazar José de la.fuente Instituto de Investigación en Recursos Cinegéticos IREC(CSIC-UCLM-JCCM) Unidad de Sanidad Animal Centro de Investigación y Tecnología Agroalimentaria(CITA) ITG Ganadero Avda. Serapio Huici 2231610 VillabaNavarraSpain departamento de Patología Animal Facultad de VeterinariaUniversity of Zaragoza department of Veterinary Pathobiology Center for Veterinary Health SciencesOklahoma State University

Brucella suis is responsible for swine brucellosis worldwide. Of the five different B. suis biovars （by.）, bv. 2 appears restricted to Europe where it is frequently isolated from wild boar and hares, can infect pigs and can cause human brucellosis. In this study, the differ- ential gene expression profile was characterized in spleens of Eurasian wild boar naturally infected with B. suis bv. 2. Of the 20,201 genes analyzed in the microarray, 633 and 1,373 were significantly （fold change 〉 1.8; P 〈 0.01） upregulated and downregulated, respectively, in infected wild boar. The analysis was focused on genes that were over represented after conditional test for biological process gene ontology. Upregulated genes suggested that B. suis bv. 2 infection induced cell maturation, migration and/or proliferation in infected animals. The genes downregulated in infected wild boar impaired the activity of several important cellular metabolic pathways such as metabolism, cytoskeleton organization and biogenesis, immune response and lysosomal function and vesicle-mediated transport. In addition, the response to stress, sperm fertility, muscle development and apoptosis seemed to be also impaired in infected animals. These results suggested that B. suis bv. 2 may use strategies similar to other smooth brucellae to facilitate intracellular multiplication and the development of chronic infections. To our knowledge, this is the first report of the analysis of gene expression profile in hosts infected with B. suis bv. 2, which is important to understand the molecular mechanisms at the host-pathogen interface in the main reservoir species with possible implications in the zoonotic cycle of the pathogen.

关键词： Brucella suis boar genomics microarray systems biology

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