scholarly journals Selenomethionine-Dominated Selenium-Enriched Peanut Protein Ameliorates Alcohol-Induced Liver Disease in Mice by Suppressing Oxidative Stress

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2979
Author(s):  
Lin Gao ◽  
Jiawei Yuan ◽  
Yuhuan Cheng ◽  
Mengling Chen ◽  
Genhua Zhang ◽  
...  

Numerous natural compounds are considered as potential therapeutic agents against alcohol-induced liver disease (ALD). Research shows that selenium (Se) has a variety of bioactivities, including liver protecting ability. The present study based on in vitro cell culture models and in vivo mouse models was aimed at examining the contribution of selenomethionine (SeMet)-dominated Se-enriched peanut protein (SePP) to liver protection. SeMet and especially SePP reversed cell viability and cell death, inhibited ethanol induced CYP2E1 activation, decreased reactive oxygen species level, and restored GSH level. Hence, SeMet-dominated SePP alleviates alcohol-induced AML-12 cytotoxicity by suppressing oxidative stress. The p38-dependent mechanism was found to be responsible for SePP-induced Nrf-2 activation. Furthermore, supplementation with SePP and SeMet regulated lipid metabolism and reduced oxidative stress, minimizing liver damage in mice. Selenomethionine-dominated SePP possesses potential therapeutic properties and can be used to treat ALD through the suppression of oxidative stress.

Author(s):  
Christopher S. Szot ◽  
Cara F. Buchanan ◽  
Joseph W. Freeman ◽  
Marissa Nichole Rylander

Despite the 200 billion dollars invested in cancer therapy research and development since 1971, only 5% of new drugs entering clinical trials successfully obtain FDA approval [1, 2]. There is a growing concern in the cancer research community that this slow movement in progress stems from the need for improved preclinical models for testing new therapeutic agents [1]. A burgeoning interface between cancer research and tissue engineering is transforming how tumor development is being studied in vitro. As a result, complex 3D cancer cell culture models are beginning to be developed with phenotypes representative of in vivo cancer progression [3].


2020 ◽  
Vol 17 ◽  
pp. 155076291989964
Author(s):  
Robert J. Evans ◽  
Simon A. Johnston

In our recent publication, we show for the first time that the fungal pathogen Cryptococcus neoformans is able to manipulate host cells by producing eicosanoids that mimic those found in the host. Using complementary in vivo zebrafish and in vitro macrophage cell culture models of Cryptococcus infection, we found that these eicosanoids manipulate host innate immune cells by activating the host receptor PPAR-gamma which is an important regulator of macrophage inflammatory phenotypes. We initially identified PGE2 as the eicosanoid species responsible for this effect; however, we later found that a derivative of PGE2—15-keto-PGE2—was ultimately responsible and that this eicosanoid acted as a partial agonist to PPAR-gamma. In this commentary, we will discuss some of the concepts and conclusions in our original publication and expand on their implications and future directions.


Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 47
Author(s):  
Rosy Ghanem ◽  
Véronique Laurent ◽  
Philippe Roquefort ◽  
Tanguy Haute ◽  
Sophie Ramel ◽  
...  

The respiratory epithelium can be affected by many diseases that could be treated using aerosol gene therapy. Among these, cystic fibrosis (CF) is a lethal inherited disease characterized by airways complications, which determine the life expectancy and the effectiveness of aerosolized treatments. Beside evaluations performed under in vivo settings, cell culture models mimicking in vivo pathophysiological conditions can provide complementary insights into the potential of gene transfer strategies. Such models must consider multiple parameters, following the rationale that proper gene transfer evaluations depend on whether they are performed under experimental conditions close to pathophysiological settings. In addition, the mucus layer, which covers the epithelial cells, constitutes a physical barrier for gene delivery, especially in diseases such as CF. Artificial mucus models featuring physical and biological properties similar to CF mucus allow determining the ability of gene transfer systems to effectively reach the underlying epithelium. In this review, we describe mucus and cellular models relevant for CF aerosol gene therapy, with a particular emphasis on mucus rheology. We strongly believe that combining multiple pathophysiological features in single complex cell culture models could help bridge the gaps between in vitro and in vivo settings, as well as viral and non-viral gene delivery strategies.


2020 ◽  
Author(s):  
C. Calitz ◽  
N. Pavlovic ◽  
J. Rosenquist ◽  
C. Zagami ◽  
A. Samanta ◽  
...  

ABSTRACTHepatocellular carcinoma (HCC) is a primary liver tumor developing in the wake of chronic liver disease. Chronic liver disease and inflammation leads to a fibrotic environment actively supporting and driving hepatocarcinogenesis. Insight into hepatocarcinogenesis in terms of the interplay between the tumor stroma micro-environment and tumor cells is thus of considerable importance. Three-dimensional (3D) cell culture models are proposed as the missing link between current in vitro 2D cell culture models and in vivo animal models. Our aim was to design a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature. Physiologically relevant hydrogels such as collagen and fibrinogen were incorporated to mimicking the bio-physical properties of the tumor ECM. In our model LX2 and HepG2 cells embedded in a hydrogel matrix were seeded onto the inverted insert membrane of a Transwell™ system. HUVEC cells were then seeded onto the opposite side of the membrane. Three formulations consisting of ECM-hydrogels embedded with cells were prepared and the bio-physical properties determined by rheology. Cell viability was determined by the AlamarBlue® assay over 21-days. The effect of the chemotherapeutic drug doxorubicin was evaluated in both a 2D co-culture and our 3D model for a period of 72h. We show that this model is viable for 25-days and gives rise to metastatic tumor nodules after 17 days in culture. Rheology results show that bio-physical properties of a fibrotic, cirrhotic and HCC liver can be successfully mimicked. Overall, results indicate that this 3D model is more representative of the in vivo situation compared to traditional 2D cultures. Our 3D tumor model showed a decreased response to chemotherapeutics, mimicking drug resistance typically seen in HCC patients. This model could in future provide a valuable new platform to study multifocal HCC or to identify mechanisms that contribute to early stages of metastasis.SUMMARYA protocol for a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature, to study endocrine and paracrine signaling in liver cancer. The model uses physiological relevant hydrogels in ratios mimicking the bio-physical properties of the stromal extracellular matrix, which is an active mediator of cellular interactions, tumor growth and metastasis.


2001 ◽  
Vol 119 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Ray A. Caldwell ◽  
Barbara R. Grubb ◽  
Robert Tarran ◽  
Richard C. Boucher ◽  
Michael R. Knowles ◽  
...  

The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl−] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl−] in the “thin” ASL (∼30 μm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl−] in vivo. In initial experiments, the electrode measured [Cl−] in physiologic salt solutions, small volume (7.6 μl) test solutions, and in in vitro cell culture models, with ≥93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl− measurements were made in the following airway regions and species. First, ASL [Cl−] was measured in normal human nasal cavity and averaged 117.3 ± 11.2 mM (n = 6). Second, ASL [Cl−] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 ± 1.8 mM; (n = 6) and 126.9 ± 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 ± 4.2 mM (n = 13); and monkey bronchus = 112.3 ± 10.9 mM (n = 3). Third, Cl− measurements were made in small (1–2 mm) diameter airways of the rabbit (108.3 ± 7.1 mM, n = 5) and monkey (128.5 ± 6.8 mM, n = 3). The measured [Cl−], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology.


2012 ◽  
Vol 4 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Barbara Rothen-Rutishauser ◽  
Martin J.D. Clift ◽  
Corinne Jud ◽  
Alke Fink ◽  
Peter Wick

AbstratThe human body can be exposed to nanomaterials through a variety of different routes. As nanomaterials get in contact with the skin, the gastrointestinal tract, and the respiratory tract, these biological compartments are acting as barriers to the passage of nano-sized materials into the organism. These structural and functional barriers are provided by the epithelia serving as an interface between biological compartments. In order to initiate the reduction, refinement and replacement of time consuming, expensive and stressful (to the animals) in vivo experimental approaches, many in vitro epithelial cell culture models have been developed during the last decades. This review therefore, focuses on the functional as well as structural aspects of epithelial cells as well as the most commonly used in vitro epithelial models of the primary biological barriers with which nanomaterials might come in contact with either occupationally, or during their manufacturing and application. The advantages and disadvantages of the different in vitro models are discussed in order to provide a clear overview as to whether or not epithelial cell cultures are an advantageous model to be used for basic mechanism and nanotoxicology research.


2021 ◽  
Vol 9 (6) ◽  
pp. 1262
Author(s):  
Emanuel Vamanu ◽  
Laura Dorina Dinu ◽  
Diana Roxana Pelinescu ◽  
Florentina Gatea

Edible mushrooms are functional foods and valuable but less exploited sources of biologically active compounds. Herbal teas are a range of products widely used due to the therapeutic properties that have been demonstrated by traditional medicine and a supplement in conventional therapies. Their interaction with the human microbiota is an aspect that must be researched, the therapeutic properties depending on the interaction with the microbiota and the consequent fermentative activity. Modulation processes result from the activity of, for example, phenolic acids, which are a major component and which have already demonstrated activity in combating oxidative stress. The aim of this mini-review is to highlight the essential aspects of modulating the microbiota using edible mushrooms and herbal teas. Although the phenolic pattern is different for edible mushrooms and herbal teas, certain non-phenolic compounds (polysaccharides and/or caffeine) are important in alleviating chronic diseases. These specific functional compounds have modulatory properties against oxidative stress, demonstrating health-beneficial effects in vitro and/or In vivo. Moreover, recent advances in improving human health via gut microbiota are presented. Plant-derived miRNAs from mushrooms and herbal teas were highlighted as a potential strategy for new therapeutic effects.


2018 ◽  
Vol 9 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Mar Pérez ◽  
Miguel Medina ◽  
Félix Hernández ◽  
Jesús Avila

AbstractThe microtubule-associated protein Tau plays a crucial role in stabilizing neuronal microtubules. In Tauopathies, Tau loses its ability to bind microtubules, detach from them and forms intracellular aggregates. Increasing evidence in recent years supports the notion that Tau pathology spreading throughout the brain in AD and other Tauopathies is the consequence of the propagation of specific Tau species along neuroanatomically connected brain regions in a so-called “prion-like” manner. A number of steps are assumed to be involved in this process, including secretion, cellular uptake, transcellular transfer and/or seeding, although the precise mechanisms underlying propagation of Tau pathology are not fully understood yet. This review summarizes recent evidence on the nature of the specific Tau species that are propagated and the different mechanisms of Tau pathology spreading.


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