scholarly journals The Role of the IL-23/IL-17 Axis in Disease Initiation in Spondyloarthritis: Lessons Learned From Animal Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohamed Mandour ◽  
Sijia Chen ◽  
Marleen G. H. van de Sande
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Preventive Treatment ◽  
Axial Skeleton ◽  
Lessons Learned ◽  
Necrosis Factor Alpha ◽  
Initiation Phase ◽  
Disease Initiation

Spondyloarthritis (SpA) is a spectrum of chronic inflammatory joint diseases that frequently presents with inflammation of the axial skeleton, peripheral joints, entheses, skin, and gut. Understanding SpA pathogenesis has been proven challenging due to the limited availability of human target tissues. In recent years, the interleukin (IL)-23/IL-17 pathway has been implicated in the pathogenesis of SpA, in addition to the Tumor Necrosis Factor Alpha (TNF-α) cytokine. The underlying molecular mechanisms by which the IL-23/IL-17 pathway triggers disease initiation, both in the joints as well as at extra-musculoskeletal sites, are not precisely known. Animal models that resemble pathological features of human SpA have provided possibilities for in-depth molecular analyses of target tissues during various phases of the disease, including the pre-clinical initiation phase of the disease before arthritis and spondylitis are clinically present. Herein, we summarize recent insights gained in SpA animal models on the role of the IL-23/IL-17 pathway in immune activation across affected sites in SpA, which include the joint, entheses, gut and skin. We discuss how local activation of the IL-23/IL-17 axis may contribute to the development of tissue inflammation and the onset of clinically manifest SpA. The overall aim is to provide the reader with an overview of how the IL-23/IL-17 axis could contribute to the onset of SpA pathogenesis. We discuss how insights from animal studies into the initiation phase of disease could instruct validation studies in at-risk individuals and thereby provide a perspective for potential future preventive treatment.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

scholarly journals Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

2021 ◽  
Vol 22 (14) ◽  
pp. 7256
Author(s):  
Vianet Argelia Tello-Flores ◽  
Fredy Omar Beltrán-Anaya ◽  
Marco Antonio Ramírez-Vargas ◽  
Brenda Ely Esteban-Casales ◽  
Napoleón Navarro-Tito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Species ◽  
Necrosis Factor Alpha ◽  
Polypyrimidine Tract Binding Protein ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

ANTI-EPILEPTIC DRUGS AND BRAIN AND BEHAVIOURAL DEVELOPMENT IN ANIMAL MODELS AND HUMANS

2010 ◽  
Vol 21 (4) ◽  
pp. 283-306
Author(s):  
NAGHME ADAB ◽  
MICHAEL F O'DONOGHUE
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Developmental Problems ◽  
Gestational Exposure ◽  
Behavioural Effects ◽  
Confounding Variables ◽  
Long Time ◽  
Behavioural Repertoire ◽  
Rule Out

Women with epilepsy constitute about 0.6% of pregnancies. The potential for major structural malformations following gestational exposure to anti-epileptic drugs (AEDs) is well known and causes concern as how best to manage epilepsy during pregnancy. In this review we focus on the structural and functional effects on the developing brain to complement other recent reviews. We do not cover neural tube defects which have been reviewed elsewhere. Suffice to say that carbamazepine, lamotrigine and, in particular, valproate exposure are associated with them. We discuss studies based on animal models as well as those that have followed-up children exposed to AEDs in-utero. Careful longitudinal human research can document the cognitive and behavioural effects, but the long time scales required and inability to rule out confounding variables, both genetic and environmental, are serious limitations. Animal studies are based on the assumption that many developmental processes are conserved between the animals used in the models (most often rodents) and humans. However, the hugely expanded cortex and cognitive and behavioural repertoire of humans implies that there are aspects that can not be well modelled. In addition, due to differences in how susceptible different species are to various teratogens, studies always need to be done in man as well. Nevertheless, an understanding of the molecular mechanisms of neuro-teratogenesis derived from animal models will help us predict which anti-epileptic drugs are likely to cause fewer neuro-developmental problems in humans.

scholarly journals Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1142 ◽  
Author(s):  
Yining Jin ◽  
Harini Acharya ◽  
Devansh Acharya ◽  
Rick Jorgensen ◽  
Haoran Gao ◽  
...  
Keyword(s):  
Animal Models ◽  
Molecular Mechanisms ◽  
Public Health Issue ◽  
Wheat Allergy ◽  
Comprehensive Review ◽  
Testing Tools ◽  
Epitope Structure ◽  
Wheat Products ◽  
And Control

The prevalence of wheat allergy has reached significant levels in many countries. Therefore, wheat is a major global food safety and public health issue. Animal models serve as critical tools to advance the understanding of the mechanisms of wheat allergenicity to develop preventive and control methods. A comprehensive review on the molecular mechanisms of wheat allergenicity using animal models is unavailable at present. There were two major objectives of this study: To identify the lessons that animal models have taught us regarding the molecular mechanisms of wheat allergenicity and to identify the strengths, challenges, and future prospects of animal models in basic and applied wheat allergy research. Using the PubMed and Google Scholar databases, we retrieved and critically analyzed the relevant articles and excluded celiac disease and non-celiac gluten sensitivity. Our analysis shows that animal models can provide insight into the IgE epitope structure of wheat allergens, effects of detergents and other chemicals on wheat allergenicity, and the role of genetics, microbiome, and food processing in wheat allergy. Although animal models have inherent limitations, they are critical to advance knowledge on the molecular mechanisms of wheat allergenicity. They can also serve as highly useful pre-clinical testing tools to develop safer genetically modified wheat, hypoallergenic wheat products, novel pharmaceuticals, and vaccines.

scholarly journals Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 594 ◽  
Author(s):  
Daniela Pellegrino ◽  
Daniele La Russa ◽  
Alessandro Marrone
Keyword(s):  
Risk Factors ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Public Health Problem ◽  
Kidney Damage ◽  
Major Public Health Problem ◽  
Altered Expression ◽  
Oxidative Balance ◽  
Increased Risk

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.

scholarly journals Trigeminal neuralgia and genetics: A systematic review

2021 ◽  
Vol 17 ◽  
pp. 174480692110161
Author(s):  
Mari Aaroe Mannerak ◽  
Aslan Lashkarivand ◽  
Per Kristian Eide
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Trigeminal Neuralgia ◽  
Animal Studies ◽  
Genetic Factors ◽  
Web Of Science ◽  
Cochrane Library ◽  
Trigeminal Pain ◽  
Familial Form

Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1–2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.

scholarly journals Diet and Skin Cancer: The Potential Role of Dietary Antioxidants in Nonmelanoma Skin Cancer Prevention

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Rajani Katta ◽  
Danielle Nicole Brown
Keyword(s):  
Skin Cancer ◽  
Cancer Prevention ◽  
Uv Radiation ◽  
Animal Studies ◽  
Potential Role ◽  
Nonmelanoma Skin Cancer ◽  
Lessons Learned ◽  
Skin Cancer Prevention ◽  
Whole Foods

Nonmelanoma skin cancer (NMSC) is the most common cancer among Americans. Ultraviolet (UV) radiation exposure is the major risk factor for the development of NMSC. Dietary AOs may prevent free radical-mediated DNA damage and tumorigenesis secondary to UV radiation. Numerous laboratory studies have found that certain dietary AOs show significant promise in skin cancer prevention. These results have been substantiated by animal studies. In human studies, researchers have evaluated both oral AO supplements and dietary intake of AOs via whole foods. In this review, we provide an overview of the role of AOs in preventing tumorigenesis and outline four targeted dietary AOs. We review the results of research evaluating oral AOs supplements as compared to dietary AOs intake via whole foods. While these specific supplements have not shown efficacy, intake of AOs via consumption of whole foods has shown some promise. Lessons learned from the field of hypertension research may provide important guidance in future study design. Further research on the role of dietary AOs in the prevention of NMSC is warranted and should focus on intake via whole food consumption.

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