scholarly journals Exploring the Interface between Inflammatory and Therapeutic Glucocorticoid Induced Bone and Muscle Loss

2019 ◽  
Vol 20 (22) ◽  
pp. 5768 ◽  
Author(s):  
Justine M. Webster ◽  
Chloe G. Fenton ◽  
Ramon Langen ◽  
Rowan S. Hardy
Keyword(s):  
Inflammatory Disease ◽  
Muscle Wasting ◽  
Muscle Metabolism ◽  
Chronic Inflammatory Disease ◽  
Muscle Loss ◽  
Murine Models ◽  
Models Of Disease ◽  
Inflammatory Signalling ◽  
Synthetic Glucocorticoids

Due to their potent immunomodulatory anti-inflammatory properties, synthetic glucocorticoids (GCs) are widely utilized in the treatment of chronic inflammatory disease. In this review, we examine our current understanding of how chronic inflammation and commonly used therapeutic GCs interact to regulate bone and muscle metabolism. Whilst both inflammation and therapeutic GCs directly promote systemic osteoporosis and muscle wasting, the mechanisms whereby they achieve this are distinct. Importantly, their interactions in vivo are greatly complicated secondary to the directly opposing actions of GCs on a wide array of pro-inflammatory signalling pathways that underpin catabolic and anti-anabolic metabolism. Several clinical studies have attempted to address the net effects of therapeutic glucocorticoids on inflammatory bone loss and muscle wasting using a range of approaches. These have yielded a wide array of results further complicated by the nature of inflammatory disease, underlying the disease management and regimen of GC therapy. Here, we report the latest findings related to these pathway interactions and explore the latest insights from murine models of disease aimed at modelling these processes and delineating the contribution of pre-receptor steroid metabolism. Understanding these processes remains paramount in the effective management of patients with chronic inflammatory disease.

scholarly journals In Vivo Inflammation Does Not Impair ABCA1-Mediated Cholesterol Efflux Capacity of HDL

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Remco Franssen ◽  
Alinda W. M. Schimmel ◽  
Sander I. van Leuven ◽  
Simone C. S. Wolfkamp ◽  
Erik S. G. Stroes ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Inflammatory Disease ◽  
Cholesterol Efflux ◽  
Chronic Inflammatory Disease ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
In Vivo Inflammation ◽  
The Impact

HDL provides atheroprotection by facilitating cholesterol efflex from lipid-laden macrophages in the vessel wall. In vitro studies have suggested impaired efflux capacity of HDL following inflammatory changes. We assessed the impact of acute severe sepsis and mild chronic inflammatory disease on the efflux capacity of HDL. We hypothesize that a more severe inflammatory state leads to stronger impaired cholesterol efflux capacity. Using lipid-laden THP1 cells and fibroblasts we were able to show that efflux capacity of HDL from both patients with severe sepsis or with Crohn's disease (active or in remission), either isolated using density gradient ultracentrifugation or using apoB precipitation, was not impaired. Yet plasma levels of HDL cholesterol and apoA-I were markedly lower in patients with sepsis. Based on the current observations we conclude that inflammatory disease does not interfere with the capacity of HDL to mediate cholesterol efflux. Our findings do not lend support to the biological relevance of HDL function changes in vitro.

The Application of In Vivo MRI and MRS in Phenomic Studies of Murine Models of Disease

2018 ◽  
pp. 19-62
Author(s):  
Po-Wah So ◽  
Azhaar Ashraf ◽  
Alice Marie Sybille Durieux ◽  
William Richard Crum ◽  
Jimmy David Bell
Keyword(s):  
Murine Models ◽  
Models Of Disease

The Application of In Vivo MRI and MRS in Phenomic Studies of Murine Models of Disease

2017 ◽  
pp. 1-44
Author(s):  
Po-Wah So ◽  
Azhaar Ashraf ◽  
Alice Marie Sybille Durieux ◽  
William Richard Crum ◽  
Jimmy David Bell
Keyword(s):  
Murine Models ◽  
Models Of Disease

scholarly journals HuR counteracts miR-330 to promote STAT3 translation during inflammation-induced muscle wasting

2019 ◽  
Vol 116 (35) ◽  
pp. 17261-17270 ◽  
Author(s):  
Souad Mubaid ◽  
Jennifer F. Ma ◽  
Amr Omer ◽  
Kholoud Ashour ◽  
Xian J. Lian ◽  
...  
Keyword(s):  
Muscle Wasting ◽  
Rna Binding ◽  
Fiber Formation ◽  
Muscle Loss ◽  
Translation Inhibition ◽  
The Stability ◽  
Transcription 3 ◽  
Cellular Movement

Debilitating cancer-induced muscle wasting, a syndrome known as cachexia, is lethal. Here we report a posttranscriptional pathway involving the RNA-binding protein HuR as a key player in the onset of this syndrome. Under these conditions, HuR switches its function from a promoter of muscle fiber formation to become an inducer of muscle loss. HuR binds to the STAT3 (signal transducer and activator of transcription 3) mRNA, which encodes one of the main effectors of this condition, promoting its expression both in vitro and in vivo. While HuR does not affect the stability and the cellular movement of this transcript, HuR promotes the translation of the STAT3 mRNA by preventing miR-330 (microRNA 330)–mediated translation inhibition. To achieve this effect, HuR directly binds to a U-rich element in the STAT3 mRNA-3′untranslated region (UTR) located within the vicinity of the miR-330 seed element. Even though the binding sites of HuR and miR-330 do not overlap, the recruitment of either one of them to the STAT3-3′UTR negatively impacts the binding and the function of the other factor. Therefore, together, our data establish the competitive interplay between HuR and miR-330 as a mechanism via which muscle fibers modulate, in part, STAT3 expression to determine their fate in response to promoters of muscle wasting.

scholarly journals Microbiome and Asthma: What Have Experimental Models Already Taught Us?

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
R. Bonamichi-Santos ◽  
M. V. Aun ◽  
R. C. Agondi ◽  
J. Kalil ◽  
P. Giavina-Bianchi
Keyword(s):  
Immune System ◽  
Inflammatory Disease ◽  
Scientific Community ◽  
Inflammatory Diseases ◽  
Human Microbiome ◽  
Chronic Inflammatory Disease ◽  
Experimental Models ◽  
Murine Models ◽  
Respiratory Inflammation ◽  
The Relationship

Asthma is a chronic inflammatory disease that imposes a substantial burden on patients, their families, and the community. Although many aspects of the pathogenesis of classical allergic asthma are well known by the scientific community, other points are not yet understood. Experimental asthma models, particularly murine models, have been used for over 100 years in order to better understand the immunopathology of asthma. It has been shown that human microbiome is an important component in the development of the immune system. Furthermore, the occurrence of many inflammatory diseases is influenced by the presence of microbes. Again, experimental models of asthma have helped researchers to understand the relationship between the microbiome and respiratory inflammation. In this review, we discuss the evolution of murine models of asthma and approach the major studies involving the microbiome and asthma.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

A Critical Review on Tamaka Shwasa (Bronchial Asthma) - An Ayurvedic View

2017 ◽  
Vol 2 (3) ◽  
Author(s):  
Sandip R. Baheti ◽  
Deepa Sharma ◽  
Saroj Devi ◽  
Amit Rai
Keyword(s):  
Bronchial Asthma ◽  
Inflammatory Disease ◽  
Critical Review ◽  
Modern Science ◽  
Modern Medicine ◽  
Chronic Inflammatory Disease ◽  
The Body ◽  
Natural Immunity ◽  
Shortness Of Breath ◽  
Asthma Symptoms

Difficulty in breathing or shortness of breath may be simply termed as Shwasa (Asthma), As per Ayurveda, Shwasa is mainly caused by the Vata and Kapha Doshas. Shwasa is broadly classified into five types in Maha Shwasa (Dyspnoea major), Urdhawa Shwasa (Expiratory Dyspnoea), Chinna Shwasa (Chyne-stroke respiration), Kshudra Shwasa (Dyspnoea minor), Tamaka Shwasa (Bronchial Asthma). In modern science Tamaka Shwasa can be correlated with Asthma, Asthma which is a chronic inflammatory disease of airway. In modern medicine there is no cure for Asthma, symptoms can typically be improved. In Ayurveda, Asthma can be effectively and safely manage the condition without inducing any drug dependency where Pachakarma procedures and use of internal medication detoxifies the body, provides nutrition and increases the elasticity of lung tissue it also develops natural immunity of the body thus decreasing episodic recurrence of the disease.

Sign in / Sign up

Export Citation Format

Share Document