scholarly journals Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 766
Author(s):  
David F. Woods ◽  
Stephanie Flynn ◽  
Jose A. Caparrós-Martín ◽  
Stephen M. Stick ◽  
F. Jerry Reen ◽  
...  

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation–pathogen–host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.

2021 ◽  
Vol 12 ◽  
Author(s):  
Waqas Ahmed ◽  
Girish Neelakanta ◽  
Hameeda Sultana

Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We also highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases.


2016 ◽  
Vol 47 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Laura J. Sherrard ◽  
Stef J. McGrath ◽  
Leanne McIlreavey ◽  
Joseph Hatch ◽  
Matthew C. Wolfgang ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Francesca Mancini ◽  
Ludovica Giorgini ◽  
Emanuela Teveroni ◽  
Alfredo Pontecorvi ◽  
Fabiola Moretti

Sex profoundly affects cancer incidence and susceptibility to therapy, with sex hormones highly contributing to this disparity. Various studies and omics data suggest a relationship between sex and the oncosuppressor p53 circuitry, including its regulators MDM2 and MDM4. Association of this network with genetic variation underlies sex-related altered cancer risk, age of onset, and cancer sensitivity to therapy. Moreover, sex-related factors, mainly estrogenic hormones, can affect the levels and/or function of the p53 network both in hormone-dependent and independent cancer. Despite this evidence, preclinical and clinical studies aimed to evaluate p53 targeted therapy rarely consider sex and related factors. This review summarizes the studies reporting the relationship between sex and the p53 circuitry, including its associated regulators, MDM2 and MDM4, with particular emphasis on estrogenic hormones. Moreover, we reviewed the evaluation of sex/hormone in preclinical studies and clinical trials employing p53-target therapies, and discuss how patients’ sex and hormonal status could impact these therapeutic approaches.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Lunbiao Cui ◽  
Xiling Guo ◽  
Yuhua Qi ◽  
Xian Qi ◽  
Yiyue Ge ◽  
...  

Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. To identify cellular miRNAs involved in the host response to enterovirus 71 (EV71) infection, we performed a comprehensive miRNA profiling in EV71-infected Hep2 cells through deep sequencing. 64 miRNAs were found whose expression levels changed for more than 2-fold in response to EV71 infection. Gene ontology analysis revealed that many of these mRNAs play roles in neurological process, immune response, and cell death pathways, which are known to be associated with the extreme virulence of EV71. To our knowledge, this is the first study on host miRNAs expression alteration response to EV71 infection. Our findings supported the hypothesis that certain miRNAs might be essential in the host-pathogen interactions.


2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   


ORL ro ◽  
2016 ◽  
Vol 4 (1) ◽  
pp. 40-42
Author(s):  
Alexandra Boloș ◽  
Sebastian Cozma ◽  
Andreea Silvana Szalontay

Tinnitus is a common otologic symptom and probably the most troublesome. Tinnitus causes a number of physical and psychological consequences, that interfere with the quality of life of the patient. Many authors believe that the presence of tinnitus in children is a matter of lesser importance than in adults because it is met less frequently and would be a fleeting symptom, inoffensive for them (Graham, 1981). In addition, the prevalence of tinnitus during adolescence and even in young adults is increasing, possibly as a consequence of the increased ambient noise (Bulbul SF, Shargorodsky J). Various therapeutic approaches have generated different results, which led us to consider the role of psychological factors, hence the need to underline the particularities of this symptom in childhood.  


2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.


Author(s):  
MT Congedo ◽  
GM Ferretti ◽  
D Nachira ◽  
MA Pennisi

Background: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. Methods: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. Results: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. Conclusion: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.


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