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Modeling and measuring glucose diffusion and consumption by colorectal cancer spheroids in hanging drops using integrated biosensors

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Microsystems & Nanoengineering 2022年第1期8卷 193-210页

作者： Nassim Rousset Rubén López Sandoval mario Matteo Modena Andreas Hierlemann Patrick M.Misun ETH Zürich Department of Biosystems Science and EngineeringBio Engineering LaboratoryMattenstrasse 26CH-4058 BaselSwitzerland

As 3D in vitro tissue models become more pervasive,their built-in nutrient,metabolite,compound,and waste gradients increase biological relevance at the cost of analysis *** these gradients and the resulting metabolic heterogeneity requires invasive and time-consuming *** alternative is using electrochemical biosensors and measuring concentrations around the tissue model to obtain size-dependent metabolism *** our hanging-dropintegrated enzymatic glucose biosensors,we conducted current measurements within hanging-drop compartments hosting spheroids formed from the human colorectal carcinoma cell line *** developed a physics-based mathematical model of analyte consumption and transport,considering(1)diffusion and enzymatic conversion of glucose to form hydrogen peroxide(H_(2)O_(2))by the glucose-oxidase-based hydrogel functionalization of our biosensors at the microscale;(2)H_(2)O_(2)oxidation at the electrode surface,leading to amperometric H_(2)O_(2)readout;(3)glucose diffusion and glucose consumption by cancer cells in a spherical tissue model at the microscale;(4)glucose and H_(2)O_(2)transport in our hangingdrop compartments at the macroscale;and(5)solvent evaporation,leading to glucose and H_(2)O_(2)*** model relates the measured currents to the glucose concentrations generating the *** low limit of detection of our biosensors(0.4±0.1μM),combined with our current-fitting method,enabled us to reveal glucose dynamics within our *** measuring glucose dynamics in hanging-drop compartments populated by cancer spheroids of various sizes,we could infer glucose distributions within the spheroid,which will help translate in vitro 3D tissue model results to in vivo.

关键词： diffusion hanging simplicity

Impedance Imaging of Cells and Tissues:Design and Applications

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Biomedical Engineering Frontiers 2022年第1期3卷 219-239页

作者： Raziyeh Bounik Fernando Cardes Hasan Ulusan mario M.Modena Andreas Hierlemann ETH Zürich Department of Biosystems Science and EngineeringBaselSwitzerland

Due to their label-free and noninvasive nature,impedance measurements have attracted increasing interest in biological *** in microfabrication and integrated-circuit technology have opened a route to using large-scale microelectrode arrays for real-time,high-spatiotemporal-resolution impedance measurements of biological *** this review,we discuss different methods and applications of measuring impedance for cell and tissue analysis with a focus on impedance imaging with microelectrode arrays in in vitro *** first introduce how electrode configurations and the frequency range of the impedance analysis determine the information that can be *** then delve into relevant circuit topologies that can be used to implement impedance measurements and their characteristic features,such as resolution and data-acquisition ***,we detail design considerations for the implementation of new impedance-imaging *** conclude by discussing future fields of application of impedance imaging in biomedical research,in particular applications where optical imaging is not possible,such as monitoring of ex vivo tissue slices or microelectrode-based brain implants.

关键词： impedance microelectrode analysis

Pancreatic cancer,autoimmune or chronic pancreatitis,beyond tissue diagnosis:Collateral imaging and clinical characteristics may differentiate them

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World Journal of Gastrointestinal Oncology 2023年第6期15卷 925-942页

作者： Ana I Tornel-Avelar Jose Antonio Velarde Ruiz-Velasco mario Pelaez-Luna Department of Gastroenterology Hospital Civil of Guadalajara“Fray Antonio Alcalde”Guadalajara 44340JaliscoMexico Research Division School of Medicine/Department of Gastroenterology Universidad Nacional Autonoma de México/National Institute of Medical Sciences and Nutrition“Salvador Zubiran”Tlalpan 14000Mexico CityMexico

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related ***,the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses,such as autoimmune pancreatitis(AIP)and massforming chronic pancreatitis(MFCP),making its diagnosis *** AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic *** diagnostic criteria and tools allow the precise differentiation of benign from malignant masses;however,the diagnostic accuracy is *** pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate *** is not unusual that after a thorough diagnostic evaluation,the clinician is confronted with a pancreatic mass with uncertain *** those cases,a re-evaluation must be entertained,preferably by an experienced multispecialty team including radiologists,pathologists,gastroenterologists,and surgeons,looking for disease-specific clinical,imaging,and histological hallmarks or collateral evidence that could favor a specific *** aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP,PDAC,and MFCP and to highlight those disease-specific clinical,radiological,serological,and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.

关键词： Pancreas cancer Chronic pancreatitis Autoimmune pancreatitis Pancreas mass Endoscopic ultrasound Diagnosis

Anomalous Sorption Kinetics of Self-Interacting Particles by a Spherical Trap

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Communications in Computational Physics 2022年第3期31卷 707-738页

作者： Antonio Raudino Antonio Grassi Giuseppe Lombardo Giovanni Russo Clarissa Astuto mario Corti Department of Chemical Sciences University of CataniaViale A.Doria 6-95125CataniaItaly Department of Mathematics University of CataniaViale A.Doria 6-95125 CataniaItaly Applied Mathematics and Computational Science King Abdullah University of Science and Technology(KAUST)4700ThuwalSaudi Arabia CNR-IPCF Viale F.Stagno d’Alcontres 3798158 MessinaItaly

In this paper we propose a computational framework for the investigation of the correlated motion between positive and negative ions exposed to the attraction of a bubble surface that mimics the(oscillating)cell *** we aim to investigate the role of surface traps with substances freely diffusing around the *** physical system we want to model is an anchored gas drop submitted to a diffusive flowof charged surfactants(ions).When the diffusing surfactantsmeet the surface of the bubble,they are reversibly adsorbed and their local concentration is accurately *** correlated diffusion of surfactants is described by a Poisson-Nernst-Planck(PNP)system,in which the drift term is given by the gradient of a potential which includes both the effect of the bubble and the Coulomb interaction between the *** latter term is obtained from the solution of a self-consistent Poisson *** very short Debye lengths one can adopt the so called Quasi-Neutral limit which drastically simplifies the system,thus allowing for much faster numerical *** paper has four main *** first one is to present a PNP model that describes ion charges in presence of a *** second one is to provide benchmark tests for the validation of simplified multiscale models under current development[1].The third one is to explore the relevance of the term describing the interaction among the apolar tails of the *** last one is to quantitatively explore the validity of the Quasi-Neutral limit by comparison with detailed numerical simulation for smaller and smaller Debye *** order to reach these goals,we propose a simple and efficient Alternate Direction Implicit method for the numerical solution of the non-linear PNP system,which guarantees second order accuracy both in space and time,without requiring solution of nonlinear equation at each time *** semi-implicit scheme for a simplified PNP system near quasi neutrality is also p

关键词： Spherycal trap quasi-neutrality finite differences Coulomb potential Poisson-Nernst-Planck system ADI discretization semi-implicit scheme

Photoprotection Knowledge and Photoprotective Behavior of University Students:A Cross-sectional Study in Indonesia

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International Journal of Dermatology and Venereology 2022年第3期5卷 140-148页

作者： Regina Stefani Roren Paulus mario Christopher Nana Novia Jayadi Department of Dermatology and Venereology Faculty of MedicinePelita Harapan UniversityBanten 15810Indonesia

Objective:Awareness regarding the negative effects of ultraviolet radiation are commonly neglected in Asian *** study sought to evaluate the ultraviolet radiation knowledge and photoprotective behaviors of university students in ***:This observational cross-sectional was conducted at Pelita Harapan University,***:A total of 89(45.4%)medical students and 107(54.6%)nonmedical students participated in this *** mean age was 21.03±2.03 years,and 46.4%of them had Fitzpatrick type III *** students as well as older students exhibited a higher level of knowledge regarding photoprotection(P≤0.05).Factors related to good photoprotective behaviors were sex,older age,and average expenditure on *** analysis revealed that a high level of knowledge regarding photoprotection was related to acceptable photoprotective behaviors(P=0.01;odds ratio=1.97;95%confidence interval=1.13-3.54).Conclusions:Knowledge regarding sun-related damage and practice of photoprotective behaviors were low among the *** results indicate that formal education and academic subjects should incorporate the topic of sun-related damage and promote the practice of photoprotective behaviors early on to increase awareness among populations.

关键词： sun exposure ultraviolet radiation photoprotection sunscreen knowledge behavior university students

Design and Analysis of Energy Absorbent Bioinspired Lattice Structures

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Journal of Bionic Engineering 2023年第4期20卷 1670-1686页

作者： Lucrezia Greco Federica Buccino Zhuo Xu Laura Vergani Filippo Berto mario Guagliano Seyyed Moahmmad Javad Razavi Sara Bagherifard Department of Mechanical Engineering Politecnico di MilanoMilanItaly Department of Mechanical and Industrial Engineering Norwegian University of Science and TechnologyTrondheimNorway Chemical Engineering and Materials Environment Department Sapienza University of RomeRomeItaly

The increasing demand for energy absorbent structures,paired with the need for more efficient use of materials in a wide range of engineering fields,has led to an extensive range of designs in the porous forms of sandwiches,honeycomb,and *** achieve an even better performance,an ingenious solution is to learn how biological structures adjust their configurations to absorb energy without catastrophic *** this study,we have attempted to blend the shape freedom,offered by additive manufacturing techniques,with the biomimetic approach,to propose new lattice structures for energy absorbent *** this aim we have combined multiple bio-inspirational sources for the design of optimized configurations under compressive *** lattice structures are fabricated based on the designed unit cell geometries and studied using experimental and computational *** individual effect of each bio-inspired feature has been evaluated on the energy absorbance performance of the designed *** on the design parameters of the lattices,a tuning between the strength and energy absorption could be obtained,paving the way for transition within a wide range of real-life applicative scenarios.

关键词： Energy absorbance Lattice structures Bio-inspiration Fused deposition modeling Lightweight design

Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications

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World Journal of Stem Cells 2022年第1期14卷 54-75页

作者： Carla Vicinanza Elisabetta Lombardi Francesco Da Ros Miriam Marangon Cristina Durante mario Mazzucato Francesco Agostini Stem Cell Unit Centro di Riferimento Oncologico di AvianoIRCCSAviano 33081Italy

Mesenchymal stem stromal cells(MSC)are characterized by the intriguing capacity to home toward cancer cells after systemic ***,MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against *** cancer patients,MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was ***,the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor ***,induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic *** vivo cell modifications are,thus,required to improve anti-cancer properties of *** based cellular therapy products must be handled in compliance with good manufacturing practice(GMP)*** the present review we include MSCimproving manipulation approaches that,even though actually tested at preclinical level,could be compatible with GMP *** particular,we describe possible approaches to improve MSC homing on cancer,including genetic engineering,membrane modification and cytokine ***,we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic *** conclusion,we suggest that,to configure MSC as a powerful weapon against cancer,combinations of clinical grade compatible modification protocols that are currently selected,should be introduced in the final *** standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.

关键词： Cancer Mesenchymal stem stromal cells Good manufacturing practice Homing Targeted therapy Ex vivo cell modification

Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural Mesothelioma cells

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Cancer Drug Resistance 2022年第3期5卷 814-828页

作者： mario Cioce Daniela Rutigliano Annamaria Puglielli Vito Michele Fazio Department of Medicine Laboratory of Molecular Medicine and BiotechnologyUniversity Campus Bio-Medico of RomeRome 00128Italy Institute of Translational Pharmacology National Research Council of Italy(CNR)Rome 00133Italy

Aim:Malignant pleural mesothelioma is a chemoresistant tumor,and biphasic and sarcomatoid histologies portend the worst prognosis for malignant pleural mesothelioma(MPM)*** obtained the microRNA expression profile of three biphasic-sarcomatoid MPM cell lines to identify commonly expressed microRNAs and evaluate the effect of butein,a chemo-sensitizing compound,on this microRNA ***:Nanostring-based microRNA profiling and analysis through the ROSALIND platform were employed to identify the commonly modulated microRNAs and their ***-mimic transfection,Luciferase assay,and Western blotting were employed to show specific perturbation of TWIST1 levels by ***-forming assays,invasion assay,and metabolic profiling were used to assess the biological consequences of the butein-instigated miR-186-5p-mediated perturbation of TWIST1 *** analysis was used to search for the correlation between TWIST1 and miR-186-5p levels in biphasic and epithelioid MPM ***:We identified a set of perturbed microRNAs,common to three biphasic/sarcomatoid MPM cell lines,after butein *** focusing on miR-186-5p,we unraveled a butein-ignited and miR-186-5p-mediated modulation of TWIST1 levels which affected the 3D anchorage-independent growth,cisplatin resistance,invasion,and bioenergetics of the MPM cell lines *** showed that miR-186-5p and TWIST1 levels are anti-correlated in biphasic MPM specimens from ***:We unraveled a novel mechanism of action of butein,which attenuated the pro-tumorigenic features of MPM at least through a miR-186-5p-TWIST1 *** suggest that those activities converge into the chemo-sensitizing effect of this compound and may be of translational relevance.

关键词： Mesothelioma butein miR-186-5p TWIST1 pithelial-to-mesenchymal transition(EMT) chemoresistance cancer metabolism invasion anchorage-independent growth

Entropy and Cosmological Constant of a Universe Calculated by Means of Dimensional Analysis, Margolus-Levitin Theorem and Landauer’s Principle

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Journal of Modern Physics 2023年第10期14卷 1310-1322页

作者： mario Leo Dipartimento di Matematica e Fisica ‘‘Ennio De Giorgi’’ Università del Salento Lecce Italy

By means of the dimensional analysis a spherically simmetric universe with a mass M = c3/(2HG) and radius equal to c/H is considered, where H is the Hubble constant, c the speed of light and G the Newton gravitational constant. The density corresponding to this mass is equal to the critical density ρcr = 3H2/(8πG). This universe evolves according to a Bondi-Gold-Hoyle scenario, with continuous creation of matter at a rate such to maintain, during the expansion, the density always critical density. Using the Margolus-Levitin theorem and the Landauer’s principle, an entropy is associated with this universe, obtaining a formula having the same structure as the Bekenstein-Hawking formula of the entropy of a black hole. Furthermore, a time-dependent cosmological constant Λ, function of the Hubble constant and the speed of light, is proposed.

关键词： Cosmological Models Cosmological Constant Entropy