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Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor

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Bioactive Materials 2023年第10期28卷 183-195页

作者： Kihak Gwon Daheui Choi jose mde hoyos-vega Harihara Baskaran Alan M.Gonzalez-Suarez Seonhwa Lee Hye Jin Hong Kianna M.Nguyen Ether Dharmesh Go Sugahara Yuji Ishida Takeshi Saito Gulnaz Stybayeva Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMNUSA Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOHUSA Biomedical Engineering Saint Louis UniversitySt.LouisMOUSA University of Southern Californi1 Keck School of MedicineDepartment of MedicineDivision of Gastrointestinal and Liver DiseasesLos AngelesCAUSA Research and Development Department PhoenixBioCo.LtdKagamiyam1Higashi-Hiroshim1Hiroshim1Japan USC Research Center for Liver Diseases Los AngelesCAUSA

The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other cells.This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids.These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors.We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes.We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 signaling.Overall,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.

关键词： Droplet microfluidics Bioactive microcapsules Hepatocyte spheroid Heparin Hepatocyte growth factor

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Modeling gut neuro-epithelial connections in a novel microfluidic device

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Microsystems & Nanoengineering 2023年第6期9卷 235-246页

作者： jose M.de hoyos-vega Xi Yu Alan M.Gonzalez-Suarez Sisi Chen Arnaldo Mercado-Perez Eugene Krueger Jeric Hernandez Yaroslav Fedyshyn Brooke R.Druliner David R.Linden Arthur Beyder Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMNUSA Enteric Neuroscience Program(ENSP) Mayo ClinicRochesterMNUSA Division of Gastroenterology and Hepatology Department of MedicineMayo ClinicRochesterMNUSA

The intestinal lumen is filled with diverse chemical and physical stimuli.Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function.Yet,the neuro-epithelial connections remain poorly resolved,in part because the tools for orchestrating interactions between these cellular compartments are lacking.We describe the development of a two-compartment microfluidic device for co-culturing enteric neurons with intestinal epithelial cells.The device contains epithelial and neuronal compartments connected by microgrooves.The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids.We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week.In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons(IPANs)from transgenic mice that expressed the fluorescent protein tdTomato.IPANs extended projections into microgrooves,surrounded and frequently made contacts with epithelial cells.The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment.Our microfluidic device represents a platform that may,in the future,be used to dissect structure and function of neuro-epithelial connections in the gut and other organs(skin,lung,bladder,and others)in health and disease.

关键词： fluid bladder organs

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A versatile microfluidic device for multiple ex vivo/ in vitro tissue assays unrestrained from tissue topography

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Microsystems & Nanoengineering 2020年第1期6卷 806-819页

作者： jose M.de hoyos-vega Alan M.Gonzalez-Suarez jose L.Garcia-Cordero Unidad Monterrey Centro de Investigacion y de Estudios Avanzados del IPNVia del conocimiento 201Parque PIITApodacaNL 66628Mexico

Precision-cut tissue slices are an important in vitro system to study organ function because they preserve most of the native cellular microenvironments of organs,including complex intercellular connections.However,during sample manipulation or slicing,some of the natural surface topology and structure of these tissues is lost or damaged.Here,we introduce a microfluidic platform to perform multiple assays on the surface of a tissue section,unhindered by surface topography.The device consists of a valve on one side and eight open microchannels located on the opposite side,with the tissue section sandwiched between these two structures.When the valve is actuated,eight independent microfluidic channels are formed over a tissue section.This strategy prevents cross-contamination when performing assays and enables parallelization.Using irregular tissues such as an aorta,we conducted multiple in vitro and ex vivo assays on tissue sections,including short-term culturing,a drug toxicity assay,a fluorescence immunohistochemistry staining assay,and an immune cell assay,in which we observed the interaction of neutrophils with lipopolysaccharide(LPS)-stimulated endothelium.Our microfluidic platform can be employed in other disciplines,such as tissue physiology and pathophysiology,morphogenesis,drug toxicity and efficiency,metabolism studies,and diagnostics,enabling the conduction of several assays with a single biopsy sample.

关键词： metabolism topography versatile

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Irbesartan desmotropes:Solid-state characterization,thermodynamic study and dissolution properties

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Journal of Pharmaceutical Analysis 2019年第5期9卷 339-346页

作者： Andrea Mariela Araya-Sibaja Carlos Eduardo Maduro de Campos Cinira Fandaruff jose Roberto vega-Baudrit Teodolito Guillen-Giron Mirtha Navarro-hoyos Silvia Lucía Cuffini Laboratorio Nacional de Nanotecnología LANOTEC-CeNAT-CONARE 1174-1200 Pavas San Jose Costa Rica Escuela de Ciencia e Ingeniería de los Materiales Tecnologico de Costa Rica Cartago 159-7050 Costa Rica Escuela de Química Universidad de Costa Rica San Pedro de Montes de Oca 2060 San Jose Costa Rica Programa de Pos-Graduacao em Física Universidade Federal de Santa Catarina Florianopolis Brazil Independent Researcher 06472-005 Barueri Sao Paulo Brazil Laboratorio de Investigacion y Tecnología de Polímeros POLIUNA Escuela de Química Universidad Nacional de Costa Rica Heredia 86-3000 Costa Rica Instituto de Ciencia e Tecnica Universidade Federal de Sao Paulo Sao Jose dos Campos Sao Paulo Brazil

Irbesartan (IBS) is a tetrazole derivative and antihypertensive drug that has two interconvertible structures, 1H- and 2H-tautomers. The difference between them lies in the protonation of the tetrazole ring. In the solid-state, both tautomers can be isolated as crystal forms A (1H-tautomer) and B (2H-tautomer). Studies have reported that IBS is a polymorphic system and its forms A and B are related monotropically. These reports indicate form B as the most stable and less soluble form. Therefore, the goal of this contribution is to demonstrate through a complete solid-state characterization, thermodynamic study and dissolution properties that the IBS forms are desmotropes that are not related monotropically. However, the intention is also to call attention to the importance of conducting strict chemical and in solid-state quality controls on the IBS raw materials. Hence, powder X-ray diffraction (PXRD) and Raman spectroscopy (RS) at ambient and non-ambient conditions, differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) techniques were applied. Furthermore, intrinsic dissolution rate (IDR) and structural stability studies at 98% relative humidity (RH), 25℃ and 40 ℃ were conducted as well. The results show that in fact, form A is approximately four-fold more soluble than form B. In addition, both IBS forms are stable at ambient conditions. Nevertheless, structural and/or chemical instability was observed in form B at 40℃ and 98% RH. IBS has been confirmed as a desmotropic system rather than a polymorphic one. Consequently, forms A and B are not related monotropically.

关键词： Irbesartan Solid-state characterization Intrinsic dissolution rate Tautomerism Desmotropic forms

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Nasopharyngeal neuroglial heterotopy-Choristoma:Case report and review of the literature

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2021年第4期7卷 318-321页

作者： Maria Monica Baquero-hoyos joseAntonio Marino jose Luis Mayorga Department of Pediatric Otolaryngology-National Institute of Pediatrics Mexico CityMexico Attending Physician Department of Pediatric Otolaryngology-National Institute of Pediatrics Mexico CityMexico

We describe the case of a nine-month-old patient with a nasopharyngeal choristoma.The case presented includes the retrospective review of the historical,radiological,surgical and histological assessment of this pathology as well as a literature review of this entity.This case was presented in an infant with difficulty feeding,nasal obstruction and failure to thrive,evaluated with flexible nasal endoscopy,CT and MRI.The lesion was then surgically removed without complications.Nasopharyngeal choristoma is a rare congenital nonmalignant mass,which may present within a range of symptoms and severity according to its size,growth and location.

关键词： Choristoma Neuroglial heterotopy Nasopharynx

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Tests Management in CALIPSOneo: A mde Solution

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Journal of Software Engineering and Applications 2014年第6期7卷 506-512页

作者： Alberto Salido Julian Alberto Garcia Garcia jose Ponce Javier Jesus Gutierrez Software Engineering and Early Testing Group Universidad de Sevilla Sevilla Spain

Testing in Software Engineering is one of the most important phases although, unfortunately, it cannot be always successfully fulfilled due to time constraints. In most cases, the development phase takes more time than it was estimated, entailing negative effects on the testing phase. The delay increases even more in Research and Development (R + D) projects, where the real time to execute tasks is more difficult to control. Model Driven Engineering (mde) offers a solution to avoid testing costs without affecting the execution quality of the applied test. This paper presents a practical overview of a Model Driven Testing (MDT)-based methodology and its impact on CALIPSOneo project, which was carried out in liaison with Airbus Defense and Space and, particularly, with the Product Lifecycle Management (PLM) department.

关键词： Model-Driven Testing Model-Driven Engineering Product Lifecycle Management

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Mercury in Canned Tuna in Spain.Is Light Tuna Really Light?

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Food and Nutrition Sciences 2013年第7期4卷 48-54页

作者： Montserrat González-Estecha María JoséMartínez-García Manuel Fuentes-Ferrer Andrés Bodas-Pinedo Alfonso Calle-Pascual JoséMaría Ordóñez-Iriarte Cristina Fernández-Pérez Nieves Martell-Claros MiguelÁngel Rubio-Herrera Emilia Gómez-hoyos JoséJesús Guillén-Pérez Trace Element Unit and Laboratory Medicine Department Instituto de Investigación SanitariaHospital Clínico San CarlosMadridSpain Universidad Politécnica CartagenaSpain Universidad Camilo jose Cela MadridSpain Department of Epidemiology Instituto de Investigación SanitariaHospital Clínico San CarlosMadridSpain Department of Pediatrics Instituto de Investigación SanitariaHospital Clínico San CarlosMadridSpain Department of Endocrinology Instituto de Investigación SanitariaHospital Clínico San CarlosMadridSpain Consejería de Sanidad y Consumo MadridSpain Hypertension Unit Instituto de Investi-gación SanitariaHospital Clínico San CarlosMadridSpain Publich Health Department CartagenaSpain Universidad de Murcia MurciaSpain

In Spain, certain population-based studies have shown high blood mercury (Hg) levels due to the high consumption of fish. Some studies have stated that one of the most consumed fish in Spain is canned tuna. Different Spanish organisms consider that it is safe to consume canned tuna as it supposedly has a low mercury content, particularly in so-called light tuna. However, in Spain light tuna is mainly yellowfin and bigeye tuna, while in other countries it is mainly skipjack tuna. This study analyzed 36 cans of the most popular brands in Spain and examined the influence of the type of tuna, packaging medium (olive oil, sunflower seed oil, water or marinade), different brands, prices and expiration dates. Mercury concentrations (mg/kg) were measured by atomic absorption spectrometry and thermal decomposition amalgamation. The medians observed were (mg/kg): light tuna: 0.314;IQR: 0.205 - 0.594, white tuna: 0.338;IQR: 0.276 - 0.558, skipjack: 0.311;IQR: 0.299 - 0.322, frigate tuna: 0.219;IQR 0.182 - 0.257 and mackerel: 0.042;IQR 0.029 -?0.074. We found statistically significant differences between white tuna, light tuna and mackerel (p = 0.004);light tuna and mackerel (p = 0.002) and white tuna and mackerel (p = 0.006). However, we found no differences between white tuna and light tuna, or among packaging medium, brands, prices or expiration dates. The limit of 0.500 mg/kg of mercury in canned tuna was exceeded by the following percentages of the cans: 33.3% of light tuna, 16.7% of white tuna, and 0% of Skipjack, frigate tuna and mackerel. The mercury content of the cans of Spanish light tuna that were analyzed was variable and high. The results of this study indicate that stricter regulation of Hg in canned tuna is necessary. Until then, it is safer to recommend that vulnerable populations such as children and pregnant women consume canned mackerel, which has a markedly lower mercury content.

关键词： Mercury Canned Tuna Spain

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