scholarly journals In Vitro Simulation of Human Colonic Fermentation: A Practical Approach towards Models’ Design and Analytical Tools

2021 ◽  
Vol 11 (17) ◽  
pp. 8135
Author(s):  
Elena Veintimilla-Gozalbo ◽  
Andrea Asensio-Grau ◽  
Joaquim Calvo-Lerma ◽  
Ana Heredia ◽  
Ana Andrés
Keyword(s):  
In Vitro Models ◽  
Research Field ◽  
Cultural Considerations ◽  
Colonic Microbiota ◽  
Influence Of Food ◽  
In Vitro Simulation ◽  
Inoculum Preparation ◽  
Analytical Tools ◽  
The Impact

The human colonic microbiota plays an important role in the food digestion process and has a key role in maintaining health status. This community of microbes is inter-individually different due to several factors that modulate its composition. Among them, diet is one of the most relevant, which, in turn, is affected by environmental, economic, and cultural considerations. These pieces of evidence have promoted the study of the influence of diet on gut microbiota and the development of in vitro models that simulate the colonic digestion of foods. This narrative review aims to present a technical approach of the in vitro gut models available to evaluate the impact of diet on human colonic microbiota. A description and comments on the main characteristics, parameters, applicability, faecal inoculum preparation, and analytical tools are made. Despite the progress of in vitro colonic digestion models and metaomic applicability in this research field, there are still some challenges to face due to the lack of a consensus on the methodologies to conduct in vitro colonic digestions and the need to integrate the metaomic data to fully understand the influence of food in human colonic microbiota.

scholarly journals Human iPSC-Derived Glia as a Tool for Neuropsychiatric Research and Drug Development

2021 ◽  
Vol 22 (19) ◽  
pp. 10254
Author(s):  
Johanna Heider ◽  
Sabrina Vogel ◽  
Hansjürgen Volkmer ◽  
Ricarda Breitmeyer
Keyword(s):  
Drug Development ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
In Vitro Models ◽  
Neuropsychiatric Diseases ◽  
Culture Models ◽  
Target Screening ◽  
Induced Pluripotent ◽  
The Impact

Neuropsychiatric disorders such as schizophrenia or autism spectrum disorder represent a leading and growing burden on worldwide mental health. Fundamental lack in understanding the underlying pathobiology compromises efficient drug development despite the immense medical need. So far, antipsychotic drugs reduce symptom severity and enhance quality of life, but there is no cure available. On the molecular level, schizophrenia and autism spectrum disorders correlate with compromised neuronal phenotypes. There is increasing evidence that aberrant neuroinflammatory responses of glial cells account for synaptic pathologies through deregulated communication and reciprocal modulation. Consequently, microglia and astrocytes emerge as central targets for anti-inflammatory treatment to preserve organization and homeostasis of the central nervous system. Studying the impact of neuroinflammation in the context of neuropsychiatric disorders is, however, limited by the lack of relevant human cellular test systems that are able to represent the dynamic cellular processes and molecular changes observed in human tissue. Today, patient-derived induced pluripotent stem cells offer the opportunity to study neuroinflammatory mechanisms in vitro that comprise the genetic background of affected patients. In this review, we summarize the major findings of iPSC-based microglia and astrocyte research in the context of neuropsychiatric diseases and highlight the benefit of 2D and 3D co-culture models for the generation of efficient in vitro models for target screening and drug development.

scholarly journals Intestinal fermentation in vitro models to study food-induced gut microbiota shift: an updated review

2020 ◽  
Vol 367 (12) ◽  
Author(s):  
Lorenzo Nissen ◽  
Flavia Casciano ◽  
Andrea Gianotti
Keyword(s):  
Gut Microbiota ◽  
In Vitro Models ◽  
Experimental Conditions ◽  
Applied Microbiology ◽  
Microbial Groups ◽  
Technical Features ◽  
State Of The Science ◽  
The Impact ◽  
Small Working

ABSTRACT In vitro gut fermentation models were firstly introduced in nutrition and applied microbiology research back in the 1990s. These models have improved greatly during time, mainly over the resemblance to the complexity of digestion stages, the replication of experimental conditions, the multitude of ecological parameters to assay. The state of the science is that the most competitive models shall include a complex gut microbiota, small working volumes, distinct interconnected compartments and rigorous bio-chemical and ecological settings, controlled by a computer, as well as a free-hands accessibility, not to contaminate the mock microbiota. These models are a useful tool to study the impact of a given diet compound, e.g. prebiotics, on the human gut microbiota. The principal application is to focus on the shift of the core microbial groups and selected species together with their metabolites, assaying their diversity, richness and abundance in the community over time. Besides, it is possible to study how a compound is digested, which metabolic pathways are triggered, and the type and quantity of microbial metabolites produced. Further prospective should focus on challenges with pathogens as well as on ecology of gut syndromes. In this minireview an updated presentation of the most used intestinal models is presented, basing on their concept, technical features, as well as on research applications.

scholarly journals The future of animal production: improving productivity and sustainability

2011 ◽  
Vol 149 (S1) ◽  
pp. 9-16 ◽  
Author(s):  
D. A. HUME ◽  
C. B. A. WHITELAW ◽  
A. L. ARCHIBALD
Keyword(s):  
Agricultural Research ◽  
Wide Spectrum ◽  
Genetic Selection ◽  
Reproductive Technologies ◽  
Breeding Value ◽  
Food Needs ◽  
Analytical Tools ◽  
The Impact

SUMMARYThe challenge for the next 50 years is to increase the productivity of major livestock species to address the food needs of the world, while at the same time minimizing the environmental impact. The present review presents an optimistic view of this challenge. The completion of genome sequences, and high-density analytical tools to map genetic markers, allows for whole-genome selection programmes based on linkage disequilibrium for a wide spectrum of traits, simultaneously. In turn, it will be possible to redefine genetic prediction based on allele sharing, rather than pedigree relationships and to make breeding value predictions early in the life of the peak sire. Selection will be applied to a much wider range of traits, including those that are directed towards environmental or adaptive outcomes. In parallel, reproductive technologies will continue to advance to allow acceleration of genetic selection, probably including recombination in vitro. Transgenesis and/or mutagenesis will be applied to introduce new genetic variation or desired phenotypes. Traditional livestock systems will continue to evolve towards more intensive integrated farming modes that control inputs and outputs to minimize the impact and improve efficiency. The challenges of the next 50 years can certainly be met, but only if governments reverse the long-term disinvestment in agricultural research.

scholarly journals Effects of Saliva From Periodontally Healthy and Diseased Subjects on Barrier Function and the Inflammatory Response in in vitro Models of the Oral Epithelium

2022 ◽  
Vol 2 ◽  
Author(s):  
Antoine Roy ◽  
Amel Ben Lagha ◽  
Reginaldo Gonçalves ◽  
Daniel Grenier
Keyword(s):  
Inflammatory Response ◽  
Matrix Metalloproteinase ◽  
Barrier Function ◽  
Chronic Inflammatory Disease ◽  
In Vitro Models ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Epithelium ◽  
Chemokine Ligand ◽  
The Impact

Background: Periodontitis is a multifactorial, bacteria-mediated chronic inflammatory disease that results in the progressive destruction of the tooth-supporting tissues. It is well-known that saliva from subjects suffering from this disease generally contains higher levels of pro-inflammatory mediators, matrix metalloproteinases (MMP), and bacteria-derived toxic products. The aim of this study was to investigate and compare the effects of saliva from periodontally healthy and diseased subjects on the barrier function and inflammatory response in in vitro models of the oral epithelium.Methods: Unstimulated saliva samples from two groups of subjects, one with a healthy periodontium (n = 12) and one with severe generalized periodontitis (n = 11), were filter-sterilized. All the saliva samples were analyzed using an immunological multiplex assay to determine the levels of various cytokines and MMPs relevant to periodontitis. The impact of saliva on epithelial barrier integrity was assessed by monitoring transepithelial electrical resistance (TER) in an oral epithelium model using the B11 keratinocyte cell line. GMSM-K oral epithelial cells were treated with saliva from both groups to determine their ability to induce the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), as determined by an enzyme-linked immunosorbent assay (ELISA).Results: Saliva from the periodontitis subjects contained significantly higher concentrations of matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), IL-8, and C-X-C motif chemokine ligand 1 (CXCL1) compared to saliva from the healthy subjects. Saliva from the healthy and periodontitis subjects affected cytokine secretion and TER in a similar manner. More specifically, saliva from both groups increased TER and induced IL-6 and IL-8 secretion in the in vitro oral epithelium models used.Conclusion: Independently of the presence or absence of periodontitis, saliva can increase the relative TER and the secretion of IL-6 and IL-8 in in vitro models of the oral epithelium.

scholarly journals The impact of endocrine disruptors on oocyte competence

Reproduction ◽  
2003 ◽  
pp. 313-325 ◽  
Author(s):  
P Pocar ◽  
TA Brevini ◽  
B Fischer ◽  
F Gandolfi
Keyword(s):  
Endocrine Disruptors ◽  
In Vitro Models ◽  
Environmental Chemicals ◽  
Farm Animals ◽  
Published Data ◽  
Environmental Matrices ◽  
Oocyte Competence ◽  
Natural Hormone ◽  
The Impact

To date, approximately 60 chemicals have been identified as endocrine disruptors: exogenous agents that interfere with various aspects of natural hormone physiology. The potential reproductive and health hazards of these environmental chemicals have recently generated concern among the scientific community, policy makers and general public. The present review presents and discusses the available evidence that environmental chemicals are causing ovarian toxicity in various species, with particular attention to farm animals. The impact of chronic exposure to endocrine disruptors via food and drinking water cannot be neglected when studying fertility problems in these species. This review focuses attention on the superfamily of organochlorine chemicals, persistent organic pollutants (POPs), because of their persistence in the environment, ability to concentrate up the food chain, continued detection in environmental matrices and ability to be stored in the adipose tissue of animals and humans. Published data clearly indicate that POPs disrupt mammalian oocyte maturation and follicle physiology in every species studied so far, including farm animals. However, as most of the data available still derive from experiments performed on laboratory species or in vitro models, great care should be taken when extrapolations to other species or environmental situations are attempted.

Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats

2005 ◽  
Vol 289 (5) ◽  
pp. H1843-H1850 ◽  
Author(s):  
Ali Razmara ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Blood Vessels ◽  
In Vitro Models ◽  
Male Rats ◽  
Cerebral Blood Vessels ◽  
Treatment Groups ◽  
Protein Levels ◽  
Cox 2 ◽  
The Impact

Activation of inflammatory mechanisms contributes to cerebrovascular pathophysiology. Male gender is associated with increased stroke risk, yet little is known about the effects of testosterone in the cerebral circulation. Therefore, we explored the impact of testosterone treatment on cerebrovascular inflammation with both in vivo and in vitro models of inflammation. We hypothesized that testosterone would augment the expression of two vascular markers of cellular inflammation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Using four groups of male rats [intact, orchiectomized (ORX), and ORX treated with either testosterone (ORXT) or the testosterone metabolite 17β-estradiol (ORXE)], we determined effects of the sex hormones on cerebrovascular inflammation after intraperitoneal LPS injection. Western blot analysis showed that induction of inflammatory markers was increased in cerebral blood vessels from ORXT rats compared with intact or ORX rats. In contrast, in cerebral blood vessels from ORXE rats, there was a significant decrease in endotoxin-induced COX-2 and iNOS protein levels. Confocal microscopy of cerebral blood vessels from ORXT rats showed increased COX-2 and iNOS immunoreactivity in both endothelial and smooth muscle cells after LPS treatment. In vitro incubation with LPS also induced COX-2 in pial vessels isolated from the four animal treatment groups, with the greatest induction observed in ORXT vessels compared with the ORX and ORXE groups. Production of PGE2, a principal COX-2-derived prostaglandin end product, was also greatest in cerebral vessels isolated from ORXT rats. In conclusion, testosterone increases cerebrovascular inflammation; this effect may contribute to stroke differences between men and women.

scholarly journals Assessment of Antibody Stability in a Novel Protein-Free Serum Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 774
Author(s):  
Joachim Schuster ◽  
Vinay Kamuju ◽  
Roman Mathaes
Keyword(s):  
Improve Patient Safety ◽  
Biological Fluids ◽  
Direct Analysis ◽  
Test Methods ◽  
In Vitro Models ◽  
Stability Conditions ◽  
Accelerated Stability ◽  
The Impact

Therapeutic proteins can degrade upon administration as they are subjected to a variety of stresses in human body compartments. In vivo degradation may cause undesirable pharmacokinetic/pharmacodynamic profiles. Pre-clinical in vitro models have gained scientific interest as they enable one to evaluate the in vivo stability of monoclonal antibodies (mAbs) and ultimately can improve patient safety. We used a novel approach by stripping serum of endogenous proteins, which interfere with analytical test methods. This enabled the direct analysis of the target protein without laborious sample work-up procedures. The developed model retained the osmolality, conductivity, temperature, and pH of serum. We compared the impact of human, bovine, and artificial serum to accelerated stability conditions in histidine buffer. Target mAbs were assessed in regard to visible and sub-visible particles, as well as protein aggregation and fragmentation. Both mAbs degraded to a higher extent under physiological conditions compared to accelerated stability conditions. No relevant stability differences between the tested mAbs were observed. Our results reinforced the importance of monitoring protein stability in biological fluids or fluids emulating these conditions closely. Models enabling analysis in fluids directly allow high throughput testing in early pre-clinical stages and help in selecting molecules with increased in vivo stability.

scholarly journals Review: Challenges of In Vitro CAF Modelling in Liver Cancers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5914
Author(s):  
Alba Herrero ◽  
Elisabeth Knetemann ◽  
Inge Mannaerts
Keyword(s):  
Liver Cancer ◽  
Treatment Strategies ◽  
3D Models ◽  
Tumour Microenvironment ◽  
Current Treatment ◽  
In Vitro Models ◽  
Liver Cancers ◽  
In Vitro Systems ◽  
The Impact

Primary and secondary liver cancer are the third cause of death in the world, and as the incidence is increasing, liver cancer represents a global health burden. Current treatment strategies are insufficient to permanently cure patients from this devastating disease, and therefore other approaches are under investigation. The importance of cancer-associated fibroblasts (CAFs) in the tumour microenvironment is evident, and many pre-clinical studies have shown increased tumour aggressiveness in the presence of CAFs. However, it remains unclear how hepatic stellate cells are triggered by the tumour to become CAFs and how the recently described CAF subtypes originate and orchestrate pro-tumoural effects. Specialized in vitro systems will be needed to address these questions. In this review, we present the currently used in vitro models to study CAFs in primary and secondary liver cancer and highlight the trend from using oversimplified 2D culture systems to more complex 3D models. Relatively few studies report on the impact of cancer (sub)types on CAFs and the tumour microenvironment, and most studies investigated the impact of secreted factors due to the nature of the models.

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