scholarly journals Organ-specific LPS-induced inflammatory gene expression in adult Zebrafish

2021 ◽  
Vol 23 (5) ◽  
pp. 1069-1078
Author(s):  
Yi. Ma ◽  
A. V. Fedorov ◽  
K. A. Kondratov ◽  
A. A. Knyazeva ◽  
M. L. Vasyutina ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Danio Rerio ◽  
Multiorgan Failure ◽  
Housekeeping Genes ◽  
In Vivo Models ◽  
Hematopoietic Organ ◽  
Persistent Inflammation ◽  
Organ Specific ◽  
Inflammatory Processes

Systemic inflammation is known to be a key component of infection and non-infection diseases progression and may lead to multiorgan failure, persistent inflammation, immunosuppression, catabolism syndrome or even indolent death. This importance dictates the need for relevant in vivo models of inflammation to investigate the pathogenesis of numerous diseases and to perform drug screening. Danio rerio (zebrafish) became one of the most important models to explore biological processes in vivo. The aim of the study was to generate a lipopolysaccharide (LPS) model of systemic inflammation in vivo using zebrafish and to identify organspecific proinflammatory genes activity after intraperitoneal LPS infusion. We performed organ specific analysis of main proinflammatory genes expression in zebrafish after LPS stimulation. Comparing 18s, eef1a1l1, gapdh, and actb as potential housekeeping genes, we came to conclusion that eef1a1l1 with 99% effectiveness is the most promising for further normalization in this model. The genes activity was the most pronounced in the heart where the expression of IL6, CXCL8a, and CXCL18β was increased up to 100-fold. Moreover, the kidneys were the most involved in the inflammatory process since the highest number of analysed genes were up-regulated there: expression levels of CXCL18β, CXCL8a, IL1β, IL6, Mpeg1.2, and TNFa were significantly increased. This was probably related to the kidney activity as an immune and hematopoietic organ. The lowest reactivity was detected in the muscles. Immune reactions could be dose-dependent, for instance the infusion of 20 µg LPS led to decrease of expression of IFNy, Mpeg 1.2, and Mpeg 1.1 in the liver and to increase of Mpeg 1.2 expression in the kidney comparing with 10 µg dosage. Thus, due to the high degree of the similarity and other unique properties, Danio rerio has the advantage of being relevant model of inflammation. Our model demonstrated that the investigation of isolated zebrafish organs could be useful and informative for the investigation of inflammatory processes.

scholarly journals Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 595 ◽  
Author(s):  
Irwin K. Cheah ◽  
Barry Halliwell
Keyword(s):  
Distress Syndrome ◽  
Neuronal Damage ◽  
Multiorgan Failure ◽  
The Elderly ◽  
Ischemia And Reperfusion Injury ◽  
In Vivo Models ◽  
Dietary Amino Acid ◽  
Underlying Pathology

Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally. Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure. Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine. Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others. When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19. We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions. This review presents evidence to support that proposal.

scholarly journals Ocular Delivery of Polyphenols: Meeting the Unmet Needs

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 370
Author(s):  
Luna Krstić ◽  
María J. González-García ◽  
Yolanda Diebold
Keyword(s):  
Oxidative Stress ◽  
Polyphenolic Compounds ◽  
In Vivo Models ◽  
Structural Peculiarities ◽  
Inflammatory Processes ◽  
Delivery Strategies ◽  
Low Solubility ◽  
Ocular Therapy

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.

scholarly journals Fatty Ethanolamide of Bertholletia Excelsa Triglycerides (Brazil nuts): Anti-Inflammatory Action and Acute Toxicity Evaluation in Zebrafish (Danio rerio)

2021 ◽  
Author(s):  
Yesica Fernanda Quitian-Useche ◽  
Brenda Lorena Sánchez-Ortiz ◽  
Swanny Ferreira Borges ◽  
Benilson Ramos ◽  
Gisele Custódio de Souza ◽  
...  
Keyword(s):  
Danio Rerio ◽  
In Silico ◽  
Biological Effects ◽  
Bertholletia Excelsa ◽  
In Vivo Models ◽  
Fatty Amides ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Inflammatory Action

Abstract Fatty amides (N-alkylamides) are a group of bioactive lipids widely distributed in microorganisms, animals, and plants. The low yield in the extraction process of spilantol, a grease amide, which has been related mainly to diverse biological effects, compromises its application on a large scale. Thus, this study proposed an alternative to the synthesis of fatty amides from Bertholletia excelsa (AGBe) oil, with a chemical structure similar to that of spilantol. In vivo models induced by carrageenan were used in Zebrafish (Danio rerio). In in vivo studies, oral AGBe produced no signs of toxicity. In the histopathological study, AGBe did not cause significant changes in the main metabolizing organs (liver, kidneys, and intestines). In the anti-inflammatory evaluation, all doses (45 mg/kg, 500 mg/kg, and 1000 mg/kg) were effective, significantly reducing edema and producing a dose-response effect when compared to spilantol. In the in silico study, with the use of molecular docking, he showed that among the AGBe, the molecules 18:1, ω-7-ethanolamine and 18:1, ω-9-ethanolamine stood out, which had 21 interactions for COX-2 and 20 interactions for PLA2, respectively, surpassing the spilantol standard with 15 interactions for COX-2 and PLA2. The hypothesis of anti-inflammatory action was confirmed in the in silico study, demonstrating the involvement of AGBe in the process of inhibiting the enzymes COX-2 and PLA2. Therefore, based on all the results obtained and the fact that until the dose of 1000 mg/kg, orally, in zebrafish, it was not possible to determine the LD50, it can be said that AGBe is effective and safe for the activity anti-inflammatory.

Rho GTPase Rac1 is critical for neutrophil migration into the lung

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1257-1264 ◽  
Author(s):  
Marie-Dominique Filippi ◽  
Kathleen Szczur ◽  
Chad E. Harris ◽  
Pierre-Yves Berclaz
Keyword(s):  
Inflammatory Process ◽  
Rho Gtpase ◽  
Bone Marrow Cells ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
In Vivo Models ◽  
Rac1 Activity ◽  
Inflammatory Processes

Abstract Neutrophils are critical in the inflammatory process by moving rapidly to tissue sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42, and RhoA, are central regulators of cell migration by cytoskeleton rearrangement. The role of Rac1 in neutrophil migration related to inflammatory processes has remained elusive and has yet to be determined in physiologic in vivo models. We previously demonstrated a role for Rac1 in tail retraction. Here, we present evidence that Rac1-mediated uropod formation may be due to crosstalk with a related Rho GTPase RhoA. To assess the physiologic relevance of these findings, we used adoptive transfer of Rac1flox/flox bone marrow cells which allows postengraftment in vivo deletion of Rac1 only in blood cells. We examined the specific role of Rac1 in neutrophil migration into the lung during the inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure. The loss of Rac1 activity in neutrophils is associated with a significant decreased neutrophil recruitment into lung alveolar and attenuation of emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic integrator of signals for neutrophil recruitment into lung tissue during an inflammatory response.

scholarly journals An Intestine-on-a-Chip Model of Plug-and-Play Modularity to Study Inflammatory Processes

2020 ◽  
Vol 25 (6) ◽  
pp. 585-597 ◽  
Author(s):  
Linda Gijzen ◽  
Diego Marescotti ◽  
Elisa Raineri ◽  
Arnaud Nicolas ◽  
Henriette L. Lanz ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
In Vivo Models ◽  
Inflammatory Conditions ◽  
Human Situation ◽  
Inflammatory State ◽  
Inflammatory Processes ◽  
Factor Α ◽  
Key Aspects

Development of efficient drugs and therapies for the treatment of inflammatory conditions in the intestine is often hampered by the lack of reliable, robust, and high-throughput in vitro and in vivo models. Current models generally fail to recapitulate key aspects of the intestine, resulting in low translatability to the human situation. Here, an immunocompetent 3D perfused intestine-on-a-chip platform was developed and characterized for studying intestinal inflammation. Forty independent polarized 3D perfused epithelial tubular structures were grown from cells of mixed epithelial origin, including enterocytes (Caco-2) and goblet cells (HT29-MTX-E12). Immune cells THP-1 and MUTZ-3, which can be activated, were added to the system and assessed for cytokine release. Intestinal inflammation was mimicked through exposure to tumor necrosis factor-α (TNFα) and interleukin (IL)-1β. The effects were quantified by measuring transepithelial electrical resistance (TEER) and proinflammatory cytokine secretion on the apical and basal sides. Cytokines induced an inflammatory state in the culture, as demonstrated by the impaired barrier function and increased IL-8 secretion. Exposure to the known anti-inflammatory drug TPCA-1 prevented the inflammatory state. The model provides biological modularity for key aspects of intestinal inflammation, making use of well-established cell lines. This allows robust assays that can be tailored in complexity to serve all preclinical stages in the drug discovery and development process.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

Sign in / Sign up

Export Citation Format

Share Document