scholarly journals Molekulare Laryngologie

HNO ◽  
2021 ◽  
Author(s):  
M. Gugatschka ◽  
T. Grossmann ◽  
D. Hortobagyi
Keyword(s):  
Lamina Propria ◽  
Klinische Studien ◽  
State Of The Art ◽  
Proinflammatorische Zytokine

Zusammenfassung Hintergrund Trotz erheblicher Fortschritte in der laryngologischen Forschung gibt es eine Reihe von (benignen) Stimmlippenerkrankungen, die kausal nicht therapierbar sind. Das liegt an der eingeschränkten Zugänglichkeit sowie der sensiblen Mikroarchitektur der Stimmlippen, die nicht auf zellulärer Ebene erforscht werden können. Das pathophysiologische Verständnis endet dadurch häufig in der makroskopischen Ebene, die Folgen von Interventionen werden großteils endoskopisch oder mit indirekten Methoden evaluiert. Fragestellung Im nachfolgenden Beitrag stellen die Autor(inn)en biotechnologische State-of-the-Art-Methoden vor, die in der laryngologischen Forschung Anwendung finden, verbunden mit praktischen Beispielen. Ergebnisse Tierversuche und Zellkulturexperimente haben in den letzten Jahren zu einer signifikanten Wissenserweiterung beigetragen, dies insbesondere in den Bereichen Stimmlippeninflammation und -narbenbildung. Dem Stimmlippenfibroblasten, als wichtigstem zellulärem Bestandteil der Lamina propria, kommt dabei eine zentrale Rolle zu. Schlussfolgerungen Mittlerweile besteht bei einigen Krankheitsbildern ein tieferes Verständnis von Makroanatomie und Makropathophysiologie als je zuvor. In-vitro-Versuche zeigten beispielsweise, dass Stimmlippenfibroblasten in einem inflammatorischen Setting weniger profibrotische und proinflammatorische Zytokine sezernierten, wenn sie Vibrationen ausgesetzt sind. Umgesetzt auf die Klinik könnte das bedeuten, dass eine frühe Stimmaktivierung nach operativen Eingriffen an den Stimmlippen zu besserer Heilung und besseren stimmlichen Ergebnissen führt. Unsere Vision lautet, dass die molekulare Laryngologie ein gesichertes Fundament an Wissen bereitstellen soll, auf das in weiterer Folge klinische Studien aufgebaut werden können.

scholarly journals State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

2020 ◽  
Vol 4 ◽  
pp. 239784732097975
Author(s):  
Stéphanie Boué ◽  
Didier Goedertier ◽  
Julia Hoeng ◽  
Anita Iskandar ◽  
Arkadiusz K Kuczaj ◽  
...  
Keyword(s):  
Ad Hoc ◽  
State Of The Art ◽  
Physicochemical Characterization ◽  
Objective Evaluation ◽  
Vapor Generation ◽  
Characterization Methods ◽  
Clinical Exposure ◽  
Aerosol Generation

E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.

scholarly journals In vitro co-culture of human intestinal organoids and lamina propria-derived CD4+ T cells

2021 ◽  
Vol 2 (2) ◽  
pp. 100519
Author(s):  
Renée R.C.E. Schreurs ◽  
Martin E. Baumdick ◽  
Agata Drewniak ◽  
Madeleine J. Bunders
Keyword(s):  
T Cells ◽  
Lamina Propria ◽  
Cd4 T Cells ◽  
Intestinal Organoids

scholarly journals Fabry Disease Therapy: State-of-the-Art and Current Challenges

2020 ◽  
Vol 22 (1) ◽  
pp. 206
Author(s):  
Olga Azevedo ◽  
Miguel Fernandes Gago ◽  
Gabriel Miltenberger-Miltenyi ◽  
Nuno Sousa ◽  
Damião Cunha
Keyword(s):  
Fabry Disease ◽  
State Of The Art ◽  
Large Body ◽  
Real Life ◽  
Clinical Manifestations ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
New Therapies ◽  
Enzyme Replacement

Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that “in vitro” amenability may not always reflect “in vivo” amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.

scholarly journals State of the art on lung organoids in mammals

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Fabienne Archer ◽  
Alexandra Bobet-Erny ◽  
Maryline Gomes
Keyword(s):  
Lung Development ◽  
One Health ◽  
State Of The Art ◽  
Animal Health ◽  
In Vitro Models ◽  
Cancer Genetic ◽  
3 Dimensional ◽  
The One ◽  
Species Specific

AbstractThe number and severity of diseases affecting lung development and adult respiratory function have stimulated great interest in developing new in vitro models to study lung in different species. Recent breakthroughs in 3-dimensional (3D) organoid cultures have led to new physiological in vitro models that better mimic the lung than conventional 2D cultures. Lung organoids simulate multiple aspects of the real organ, making them promising and useful models for studying organ development, function and disease (infection, cancer, genetic disease). Due to their dynamics in culture, they can serve as a sustainable source of functional cells (biobanking) and be manipulated genetically. Given the differences between species regarding developmental kinetics, the maturation of the lung at birth, the distribution of the different cell populations along the respiratory tract and species barriers for infectious diseases, there is a need for species-specific lung models capable of mimicking mammal lungs as they are of great interest for animal health and production, following the One Health approach. This paper reviews the latest developments in the growing field of lung organoids.

Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents

2019 ◽  
Vol 14 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Roberta M. Moretti ◽  
Marina Montagnani Marelli ◽  
...  
Keyword(s):  
Cancer Prevention ◽  
State Of The Art ◽  
Synergistic Effects ◽  
The State ◽  
Therapeutic Interventions ◽  
Multiple Tumor ◽  
Anti Cancer ◽  
Important Health

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.Objective:The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.Methods:Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.Results:TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.Conclusion:The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.

scholarly journals Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice

2005 ◽  
Vol 12 (12) ◽  
pp. 1378-1386 ◽  
Author(s):  
Dionyssios N. Sgouras ◽  
Effrosini G. Panayotopoulou ◽  
Beatriz Martinez-Gonzalez ◽  
Kalliopi Petraki ◽  
Spyros Michopoulos ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lamina Propria ◽  
Serum Levels ◽  
Favorable Effect ◽  
Lactobacillus Johnsonii ◽  
Ags Cells ◽  
Inflammatory Infiltration ◽  
H Pylori

ABSTRACT In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P = 0.038) and neutrophilic (P = 0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P = 0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P = 0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.

State of the art in the production of transgenic goats

2004 ◽  
Vol 16 (4) ◽  
pp. 465 ◽  
Author(s):  
H. Baldassarre ◽  
B. Wang ◽  
C. L. Keefer ◽  
A. Lazaris ◽  
C. N. Karatzas
Keyword(s):  
Recombinant Proteins ◽  
Traditional Method ◽  
Nuclear Transfer ◽  
State Of The Art ◽  
Expression Vectors ◽  
Marketing Approval ◽  
Transfected Cells ◽  
Pronuclear Microinjection ◽  
Transgenic Goats

This review summarises recent advances in the field of transgenic goats for the purpose of producing recombinant proteins in their milk. Production of transgenic goats via pronuclear microinjection of DNA expression vectors has been the traditional method, but this results in low efficiencies. Somatic cell nuclear transfer has dramatically improved efficiencies in rates of transgenesis. Characterisation of transfected cells in vitro before use in nuclear transfer guarantees that kids born are transgenic and of predetermined gender. Using these platform technologies, several recombinant proteins of commercial interest have been produced, although none of them has yet gained marketing approval. Before these technologies are implemented in goat improvement programmes, efficiencies must be improved, costs reduced, and regulatory approval obtained for the marketing of food products derived from such animals.

scholarly journals Avaliação in vitro da resistência de duas resinas compostas submetidas a teste de compressão

2020 ◽  
Vol 8 (9) ◽  
Author(s):  
Mirla Lays Dantas de Almeida ◽  
Gymenna Maria Tenório Guênes ◽  
Luanna Abílio Diniz Melquiades de Medeiros ◽  
Mylena de Araújo Régis ◽  
Marcus Vinícius Lia Fook ◽  
...  
Keyword(s):  
Filler Content ◽  
State Of The Art ◽  
Resin Composite ◽  
Dental Materials ◽  
Santa Cruz ◽  
Porto Alegre ◽  
Composite State ◽  
Fernando Pessoa ◽  
Dent Assoc

Introdução: O aumento da demanda pela odontologia estética guiou o desenvolvimento de resinas compostas com melhores propriedades físicas e mecânicas. Por isso, percebe-se que há atualmente disponibilidade de uma grande variedade desse material. Dessa forma faz-se necessário a realização de estudos científicos acerca das resinas composta. Objetivo: Avaliar comparativamente, in vitro, à resistência de duas resinas compostas fotopolimerizáveis encontrados no mercado: a Filtek Z350 XT da 3M e a Zirconfill da Technw, após teste mecânico de compressão e análise estatística dos resultados. Material e método: Quatro amostras de cada resina composta foram submetidas ao teste de resistência à compressão numa máquina de ensaio universal. Os resultados foram analisados estatisticamente através do teste de Mann-Whitney com margem de erro 5.0%. Para digitar os dados e obter os cálculos estatísticos foi utilizado o programa IBM SPSS na versão 23. Resultados: A média da força foi mais elevada na resina Zirconfill do que na resina Z350; entretanto, a mediana foi mais elevada na resina Z350. Para a margem de erro fixada (5,0%) não há comprovação de diferença significativa (p > 0,05) entre as duas resinas em relação à força de resistência analisada. Conclusão: As resinas compostas testadas mostram valores de resistência a compressão semelhantes e não apresentam diferenças relevantes.Descritores: Resinas Compostas; Nanotecnologia; Odontologia.ReferênciasBowen RL. Use of epoxy resins in restorative materials. J Dent Res. 1956;35(3):360-69.Chagas LS. Avaliação da resistência flexural e módulo de elasticidade de uma resina do tipo Bulk Fill em comparação com uma resina convencional [monografia de conclusão de curso]. Santa Cruz do Sul: Universidade de Santa Cruz do Sul - UNISC; 2016.Behr M, Proff P, Kollbeck C, Langriegr S, Kunze J, Handel G et al. The bond strength of the resin-to-zirconia interface using diferente bonding concepts. J Mech Behav Biomed Mater. 2011;4(1):2-8.Rodrigues DS. Análise da porosidade, resistência mecânica e desgaste de cimentos de ionômero de vidro e resina composta [dissertação]. Porto: Faculdade de Ciências da Saúde, Universidade Fernando Pessoa; 2014.Pereira AFV, Miranda Junior WG. Avaliação in vitro da microinfiltração e adaptação marginal em restaurações classe v simulando lesões de abfração: estudo piloto. Arq Cent Estud Curso Odontol Univ Fed Minas Gerais. 2008;44(2):18-25.Ferracane JL. Resin composite – state of the art. Dent Mater. 2011; 27(1):29-38.Han JM, Lin H, Zheng G, Shinya A, Gomi H, Shinya A et al. Effect of nanofiller on wear resistance and surface roughness of resin composites. Chin J Dent Res. 2012;15(1):41-7.Mitra SB, Wu D, Holmes B. An application of nanotechnology in advanced dental materials. J Am Dent Assoc. 2003;134(10):1382-90.Mota EG, Weiss A, Spohr AM, Oshima HMS, Carvalho LMN. Relationship between filler content and selected mechanical properties of six microhybrid composites. Rev odonto cienc. 2011;26(2):151-55.Rosa RS. Propriedades mecânicas de resinas compostas com nanopartículas [tese]. Porto Alegre: Pontifícia Universidade Católica do Rio Grande do Sul, Faculdade de Odontologia; 2010.Souza ALT, Oliveira FMMPC, Moysés MR, Assis CPD, Ribeiro JCR, Dias SC. Avaliação da resistência à compressão de resinas compostas fotopolimerizáveis. Arq Odontol. 2007;43(1):30-5.

scholarly journals The infinite possibilities of RNA therapeutics

2021 ◽  
Author(s):  
Evelyn C Mollocana-Lara ◽  
Ming Ni ◽  
Spiros N Agathos ◽  
Fernando A Gonzales-Zubiate
Keyword(s):  
Literature Review ◽  
Antisense Oligonucleotides ◽  
State Of The Art ◽  
Small Interfering Rnas ◽  
New Era ◽  
Final Point ◽  
Clinical Investigations ◽  
General Aspects

Abstract Although the study of ribonucleic acid (RNA) therapeutics started decades ago, for many years, this field of research was overshadowed by the growing interest in DNA-based therapies. Nowadays, the role of several types of RNA in cell regulation processes and the development of various diseases have been elucidated, and research in RNA therapeutics is back with force. This short literature review aims to present general aspects of many of the molecules currently used in RNA therapeutics, including in vitro transcribed mRNA (IVT mRNA), antisense oligonucleotides (ASOs), aptamers, small interfering RNAs (siRNAs), and microRNAs (miRNAs). In addition, we describe the state of the art of technologies applied for synthetic RNA manufacture and delivery. Likewise, we detail the RNA-based therapies approved by the FDA so far, as well as the ongoing clinical investigations. As a final point, we highlight the current and potential advantages of working on RNA-based therapeutics and how these could lead to a new era of accessible and personalized healthcare.

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