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From oral formulations to drug-eluting implants:using 3D and 4D printing to develop drug delivery systems and personalized medicine

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Bio-Design and Manufacturing 2022年第1期5卷 85-106页

作者： Niels G.A.Willemen Margaretha A.J.Morsink Devin Veerman Classius F.da silva Juliana C.Cardoso Eliana B.Souto Patrícia severino Center for Biomedical Engineering Department of MedicineBrigham and Women&HospitalHarvard Medical School65 Landsdowne StreetMA 02139 CambridgeUSA Department of Developmental BioEngineering Faculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteEnschedeThe Netherlands Translational Liver Research Department of Medical Cell BioPhysicsTechnical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedeThe Netherlands Targeted Therapeutics Department of Biomaterials Science and TechnologyFaculty of Science and TechnologyUniversity of TwenteEnschedeThe Netherlands Department of Chemical Engineering Institute of EnvironmentalChemical and Pharmaceutical SciencesFederal University of São PauloRua São Nicolau210Diadema 09913‑030Brazil University of Tiradentes(Unit) and Institute of Technology and Research(ITP)Av.Murilo Dantas300Aracaju 49010‑390Brazil Faculty of Pharmacy University of CoimbraPólo das Ciências da SaúdeAzinhaga de Santa Comba3000‑548 CoimbraPortugal CEB‑Centre of Biological Engineering University of MinhoCampus de Gualtar4710‑057 BragaPortugal Tiradentes Institute 150 Mt Vernon StDorchesterMA 02125USA

Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown *** short,personalized medicine is a term that describes medical treatment that is tuned to the *** possible way to realize personalized medicine is 3D *** using materials that can be tuned upon stimulation,4D printing is *** recent years,many studies have been exploring a new field that combines 3D and 4D printing with *** has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an ***,the first 3D printed drug,Spritam®,has already found its way to the *** review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

关键词： Drug delivery systems 3D/4D printing Drug-eluting implants Microneedles Oral formulations

Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer

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Genes & Diseases 2019年第2期6卷 176-184页

作者： Fernanda S.Manoel-Caetano Ana Flávia T.Rossi Gabriela Calvet de Morais Fábio Eduardo severino Ana Elizabete silva Department of Biology UNESPSāo Paulo State UniversityCampus of Sāo Josédo Rio PretoRua Cristòvāo Colombo226515.054-000Sāo Josédo Rio PretoSāo PauloBrazil Department of Surgery and Orthopedics Faculty of MedicineUNESPSāo Paulo State UniversityCampus of BotucatuAv.Prof.Mário Rubens Guimarāes Montenegros/n18.618-687BotucatuSāo PauloBrazil

Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori *** bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial *** this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric *** v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,p<0.0001)and H2AX(RQ=2.88,p=0.0002)genes beyond the miR-421 and miR-605 in the gastric cancer *** addition,significantly elevated levels of miR-21,miR-24 and miR-421 were observed in diffuse-type gastric *** analysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction ***,our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment.

关键词： DNA damage response DNA repair Gastric cancer Gene expression microRNA

Analysis of in vivo absorption of didanosine tablets in male adult dogs by HPLC

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Journal of Pharmaceutical Analysis 2012年第1期2卷 29-34页

作者： Patrfícia severino Heloisa silva Eliana B. Souto Maria Helena A. Santana Teresa Cristina T. Dalla Costa Biotechnological Processes Development Laboratory School of Chemical Engineering State University of Campinas-UNICAMP Campinas School of Pharmacy University of Rio Grande do Sul-UFRGS School of Agrarian Science and Veterinary S o Paulo State University-UNESP Jaboticabal Faculty of Health Sciences Fernando Pessoa University (FCS-UFP) Institute of Biotechnology and Bioengineering Centre of Genomics and Biotechnology University of Trás-os-Montes and Alto Douro (CGB-UTAD/IBB)

Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.

关键词： Didanosine On-line solid phase extraction HPLC Male dogs

Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

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World Journal of Gastroenterology 2018年第47期24卷 5351-5365页

作者： Marcela Alcantara Proenca Joice Matos Biselli Maysa Succi Fábio Eduardo severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis David J Hughes Ana Elizabete silva Department of Biology UNESPUniv. Estadual PaulistaCampus of Sao Jose do Rio PretoSao Jose do Rio PretoSao Paulo 15054-000Brazil Department of Surgery and Orthopedics Faculty of MedicineUNESPUniv. Estadual PaulistaCampus of BotucatuBotucatuSao Paulo 18618-687Brazil Endoscopy Center of Rio Preto Sao Jose do Rio PretoSao Paulo 15015-700Brazil Molecular Oncology Research Center Barretos Cancer HospitalBarretosSao Paulo 14784-400Brazil Life and Health Sciences Research Institute University of MinhoCampus GualtarBraga 4710-057Portugal ICVS/3B’s-PT Government Associate Laboratory Campus GualtarBraga 4710-057Portugal Cancer Biology and Therapeutics Group UCD Conway InstituteUniversity College DublinDublin D04 V1W8Ireland

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high *** Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

关键词： Colorectal cancer Colorectal adenoma Fusobacterium nucleatum Inflammation Cytokines MicroRNAs

Performance of Cosmetic Ingredients Evaluated by Their Membrane Protection Efficiency

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Journal of Cosmetics, Dermatological Sciences and Applications 2021年第3期11卷 169-185页

作者： Daniela Rodrigues silva Maidileyvis Castro Cabello Divinomar severino Mauricio S. Baptista Departamento de Bioquímica Instituto de Química Universidade de S&#227 o Paulo S&#227 o Paulo Brazil

Plant extracts (PEs) are frequently used as ingredients in skin and hair care products to improve protection against the excess of sun exposure. PEs are usually selected based on their antioxidant capacity for reducing the damage in lipids and proteins, which are key molecules in the maintenance of skin homeostasis and hair integrity. Interestingly, biomolecules that do not have any antioxidant capacity can have a protective effect by physically adsorbing and inhibiting leakage of membranes. Our aims are: 1) to develop an experimental protocol that quantifies the level of membrane damage/protection;2) to recommend an approach to compare the membrane protection efficiency of different PEs;3) to briefly describe the mechanisms of membrane protection. Evaluation of membrane damage/protection is based on a phospholipid liposome system that signals the membrane rupture caused by photo-induced lipid oxidation. Carboxyfluorescein (CF) emission is monitored as a function of time (120 min) in a controlled experimental setup, in which a certain level of membrane damage is induced by Dimethyl-Methylene Blue (DMMB) photosensitized oxidation during red-light irradiation. Percentage levels of membrane damage/protection are calculated by comparing the CF fluorescence level of DMMB-liposomes in the presence of varying concentrations of membrane-protective ingredients with that of surfactant-dissolved DMMB-liposomes. Membrane protectants reduce the level of CF fluorescence during irradiation of DMMB-liposomes. Gallic acid (GA) and trehalose (Tre) were used as standard compounds to compute the levels of protection by the antioxidant and physical adsorption mechanisms, respectively. The percentage of membrane protection was shown to be linearly proportional to the concentration of the standard protectants. The performance of PEs was measured and compared in terms of GA or Tre membrane protection equivalents. All extracted also had their antioxidant capacities evaluate by the anti-radi

关键词： Photoprotection Antioxidants Sugars Polyphenols Flavonoids Photochemistry

Forage production and persistence characteristics of grazed native warm-season grass mixtures with or without nitrogen fertilizer

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Grassland Research 2022年第3期1卷 157-165页

作者： Caroline Nicole Chappell Marty Landon Marks Katie Michelle Mason Liliane severino da silva Joshua Luke Jacobs Mary Kimberly Mullenix Sandra Leanne Dillard Russell Brian Muntifering Department of Animal Sciences Auburn UniversityAuburnAlabamaUSA Department of Animal Science University of TennesseeKnoxvilleTennesseeUSA Department of Animal and Veterinary Sciences Clemson UniversityClemsonSouth CarolinaUSA University of Kentucky Cooperative Extension Service CarlisleKentuckyUSA

Background:Native warm-season grass(NWSG)mixtures may provide a lownitrogen(N)-input summer perennial forage option to extensively managed forage-livestock ***:Mixed pastures of big bluestem(Andropogon gerardii Vitman),little bluestem(Schizachyrium scoparium Michx.),and indiangrass(Sorghastrum nutans L.)fertilized with 0 or 67 kgNha−1 were continuously stocked with beef heifers and *** mass,nutritive value,and canopy heights were determined every 2 weeks during the grazing *** persistence measures included the canopy cover and leaf area index(LAI)and plant crown density at spring emergence following 3 years of grazing ***:Forage mass,canopy height,and stocking densities were greater for N-fertilized NWSG than unfertilized NWSG for the first 30 days of the growing season across the 3-year *** NWSG fertilized with N had a greater decrease in LAI during the growing season(51%decrease)than unfertilized *** NWSG plant density estimates following 3 years of grazing did not differ across N management ***:Forage NWSG mixtures supported superior forage attributes and greater stocking densities early in the grazing season under low-level N than zero-N-input systems and may provide a low-N-input alternative for improved species use in southeastern US forage-livestock systems.

关键词： continuous stocking grazing native warm-season grass mixtures nitrogen fertilization

Risk Factors for Cervical Cancer in a Sample Comprising Three Generations of Brazilian Women

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Journal of Cancer Therapy 2017年第1期8卷 12-25页

作者： Ilce Ferreira da silva Rosalina Jorge Koifman virgilio Augusto Gomes Parreira Simone Soares Sergio Koifman Instituto Fernandes Figueira Fundacao Oswaldo Cruz Rio de Janeiro Brazil Escola Nacional de Saúde Pública Fundacao Oswaldo Cruz Rio de Janeiro Brazil Hospital do Cancer-II Instituto Nacional do Cancer Rio de Janeiro Brazil

Background: Cervical cancer is the main cause of cancer deaths in some developing countries. Age-related cervical cancer incidence has been fundamental for understanding the different stages of carcinogenesis concepts. No Brazilian study explored the environmental risk factors involved on cervical cancer, according to age groups taking 70’s sexual revolution in Brazil as reference. Aim: To determine the prevalence of epidemiological and clinical aspects related to cervical cancer development in a sample of three age groups of Brazilian women based on 70’s sexual revolution. Methods: A cross-section study was proceeded in a hospital-based cohort of women with altered Pap-test refereed to the National Cancer Institute for Colposcopy and treatment from October 2004 to May 2006. Two register nurses interviewed all patients ascertaining risk factors and clinical characteristics. Biopsy, partial ablation were used for CIN-1, and conization was the treatment for CIN-2/3. Results: From 318 women included in the study, 42.8% were 18 - 30 years old (born after 1975), 43.4% were 31 - 49 years old (born 1955-1975), and 13.8% were 50 - 68 years old (born 1936-1954). Pregnancies (OR = 1.16;CI95%: 1.01 - 1.34) and menarche under 12 years old (OR = 1.95;CI95%: 1.17 - 3.25) were independently associated to CIN2- 3/cancer in 18 - 30 age group;menopause age (OR = 1.21;CI95%: 1.04 - 1.41) and current smoking habit (OR = 1.37;CI95%: 1.10 - 1.70) were associated to CIN2- 3/cancer in 31 - 49 age group;no statistical significance was observed for 50 - 68 age group. Conclusion: Brazilian women present distinct risk for cervical cancer according to the generation they belong, when taking the Brazilian sexual revolution on 70’s as a reference.

关键词： Cervical Cancer Cross-Section Study Epidemiology Sexual Revolution Brazil

Morphological and Optical Characterizations of CaAl2O4 Doped with Trivalent Praseodymium

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Journal of Chemistry and Chemical Engineering 2015年第8期9卷 514-516页

作者： Valeria Rejane silva Brito Raquel Jovita dos Santos Paulo Neilson Marques dos Anjos severino Alves Junior Laboratory for Research and Innovation of Advanced Materials State University of Santa Cruz llheus Bahi 45662900 Brazil Department of Fundamental Chemistry Federal University of Pernambuco Recife Pernambuco 50670901 Brazil

This work was synthesized CaAl2O4 （calcium aluminate） doped with trivalent praseodymium ions. CaAl2O4 with praseodymium 1.0% and 0.5% were synthesized. The powders of aluminates were characterized by scanning electron microscopy and luminescence ***2O4, praseodymium ions, luminescence doped with praseodymium ion that showed less porosity in its grain structure and luminescent transitions that are dependent on the wavelengths of excitation and showing both types of transitions both 5d-4f and 4f-4f.

关键词： CaAl2O4 praseodymium ions luminescence

Oily Water Treatment by Ceramic Membrane: Modeling and Simulation

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Open Journal of Fluid Dynamics 2021年第1期11卷 1-19页

作者： Adriana Barbosa da Costa Pereira Hortência Luma Fernandes Magalhães Leonardo Pereira de Lucena silva Cristiane Arcoverde Passos Ricardo Soares Gomez Balbina Raquel de Brito Correia severino Rodrigues de Farias Neto Antonio Gilson Barbosa de Lima Department of Chemical Engineering Federal University of Campina Grande Campina Grande Brazil Department of Industry Federal Institute of Paraiba Cajazeiras Brazil Department of Chemical Engineering Federal University of Paraná Curitiba Brazil Department of Mechanical Engineering Federal University of Campina Grande Campina Grande Brazil

The separation process of oily water using membranes has attracted the attention of researchers and engineers. The greater problem in the use of membrane separation process is the reduction in permeate flux due to clogged pores by oil deposition inside the membrane or by the effect of the concentration polarization. For this purpose, a theoretical study of a water/oil separation module was performed. This device consists of a tubular ceramic membrane provided with a rectangular inlet section. Numerical simulations were performed using Ansys CFX software to solve the mass and momentum conservation equations in the fluid and porous domains. Here was adopted the RNG k-ε turbulence model. The effect of the membrane porosity and the inlet velocity of the fluid mixture on the two-phase flow behavior inside the separation module were evaluated. Results of the volumetric fraction, velocity and pressure fields of the oil and water phases are presented and analyzed. The results indicate a higher oil concentration within the membrane for the cases of higher porosity, and that the inlet fluid mixture velocity does not substantially affect the velocity profile within the separation module. It is found that the maximum separation efficiency of the module was obtained with feed velocity of 40 m/s and membrane porosity of 0.44.

关键词： Ceramic Membranes Separation Process Computational Fluid Dynamics CFX