scholarly journals Opioid-Induced Immunomodulation: Consequences for the Experimental Coxsackievirus B3-Induced Myocarditis Model

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 335
Author(s):  
Kathleen Pappritz ◽  
Sophie Van Linthout
Keyword(s):  
Immune System ◽  
Severe Disease ◽  
Treatment Options ◽  
Viral Myocarditis ◽  
Coxsackievirus B3 ◽  
Specific Model ◽  
Left Ventricular ◽  
Inflammatory Disorder ◽  
Inflammatory Models ◽  
The Impact

Myocarditis is an inflammatory disorder of the heart predominantly caused by infectious agents. Since more than sixty years, the Coxsackievirus B3 (CVB3)-induced myocarditis mouse model is the experimental model used to investigate viral myocarditis. The pathogenesis of viral myocarditis is conceptually a multiphase process, initiated by the infection of cardiomyocytes, followed by activation of the immune system, and resulting in myocardial fibrosis and left ventricular dysfunction. In parallel to the direct infection of the heart, CVB3 replicates in lymphatic organs such as the pancreas. Due to infection of the pancreas, the model of experimental CVB3-induced myocarditis is estimated as a severe burden for the challenged animals. Application of analgesics in frame of the animal welfare act (European directive 2010/63/EU) is more and more becoming a matter of debate. For this purpose, we summarized published studies for 13 different opioids and discussed their potential impact on CVB3-induced myocarditis. In addition, with this summary we also want to provide guidance for researchers beyond the myocarditis field to estimate the impact of opioids on the immune system for their specific model. In the literature, both immunosuppressive as well as immune-activating effects of opioids have been described, but examinations in experimental CVB3-induced myocarditis have still not been reported so far. Based on the existing publications, administration of opioids in experimental CVB3-induced myocarditis might result in more severe disease progression, including higher mortality, or a less pronounced myocarditis model, failing to be used for the establishment of new treatment options. Taken together, the applicability of opioids in experimental CVB3-induced myocarditis and in inflammatory models in general needs to be carefully evaluated and further investigated.

scholarly journals Proteomics of Cryptococcus neoformans: From the Lab to the Clinic

2021 ◽  
Vol 22 (22) ◽  
pp. 12390
Author(s):  
Ben Muselius ◽  
Shay-Lynn Durand ◽  
Jennifer Geddes-McAlister
Keyword(s):  
Cryptococcus Neoformans ◽  
Protein Interactions ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Severe Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Protein Protein Interactions ◽  
Dynamic Relationship ◽  
The Impact

Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and causes severe disease in immunocompromised individuals around the globe with limited treatment options available. To uncover fundamental knowledge about this fungal pathogen, as well as investigate new detection and treatment strategies, mass spectrometry-based proteomics provides a plethora of tools and applications, as well as bioinformatics platforms. In this review, we highlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein–protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, which provide valuable tools to define the dynamic relationship between the host and pathogen during disease. Finally, we explore recent quantitative proteomics studies that begin to extrapolate the findings from the bench to the clinic for improved methods of fungal detection and monitoring. Such studies support a framework for personalized medical approaches to eradicate diseases caused by C. neoformans.

scholarly journals Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?

2020 ◽  
Author(s):  
Renata Silverio ◽  
Daniela Caetano Gonçalves ◽  
Márcia Fábia Andrade ◽  
Marilia Seelaender
Keyword(s):  
Body Composition ◽  
Immune System ◽  
Nutritional Status ◽  
Immune Responses ◽  
Lean Mass ◽  
Severe Disease ◽  
Cytokine Storm ◽  
Risk Of Infection ◽  
Elderly Individuals ◽  
The Impact

ABSTRACT Coronavirus disease 2019 (COVID-19) is an emerging disease that has reached pandemic status by rapidly spreading worldwide. Elderly individuals and patients with comorbidities such as obesity, diabetes, and hypertension show a higher risk of hospitalization, severe disease, and mortality by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These patients frequently show exacerbated secretion of proinflammatory cytokines associated with an overreaction of the immune system, the so-called cytokine storm. Host nutritional status plays a pivotal role in the outcome of a variety of different infectious diseases. It is known that the immune system is highly affected by malnutrition, leading to decreased immune responses with consequent augmented risk of infection and disease severity. Body composition, especially low lean mass and high adiposity, has consistently been linked to worsened prognosis in many different diseases. In this review, evidence concerning the impact of nutritional status on viral infection outcomes is discussed.

scholarly journals HLC Pair Suppression as a Risk Factor for Bacterial Bloodstream Infections and Early Mortality in Newly Diagnosed Intact Immunoglobulin Multiple Myeloma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Jose Luis Garcia de Veas Silva ◽  
Maria Trinidad Gonzalez Cejudo ◽  
Alberto Garcia Perojil Jimenez ◽  
Maria del Señor Garcia Lopez Velez ◽  
Rafael Garcia Rios Tamayo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Treatment Options ◽  
Bloodstream Infections ◽  
Early Death ◽  
High Sensitivity ◽  
Underlying Disease ◽  
Newly Diagnosed ◽  
Life Threatening ◽  
The Impact

Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system’ attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a “real world” setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.

Current era left ventricular assist devices

2021 ◽  
Author(s):  
Michael J Javorski ◽  
Anthony Zaki ◽  
Motaz Abas ◽  
Haytham Elgharably ◽  
Tamer S Attia
Keyword(s):  
Treatment Options ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist ◽  
Implantation Techniques ◽  
End Stage ◽  
The Impact

Left ventricular assist devices (LVADs) have changed the landscape of treatment options for patients with end stage heart failure. Due to the limited availability of donor hearts for transplantation, LVADs have become an important option for many of these patients. Much progress has been made in the device industry since then, and newer devices continue to improve patient outcomes. In this review, we will discuss some of the key transitions in LVADs over the years, the current LVADs used in practice today, implantation techniques, the impact of the new heart allocation system on LVAD use and future prospective LVADs.

scholarly journals The immune remodel: Weight loss-mediated inflammatory changes to obesity

2020 ◽  
Vol 245 (2) ◽  
pp. 109-121
Author(s):  
Charles L Phillips ◽  
Bernadette E Grayson
Keyword(s):  
Weight Loss ◽  
Immune System ◽  
Negative Impact ◽  
The Body ◽  
Excess Body Weight ◽  
Low Grade ◽  
Inflammatory Disorder ◽  
Organ Systems ◽  
Surgical Methods ◽  
The Impact

Obesity is an escalating world problem that contributes to the complexity and cost of treatment of metabolic disorders. Obesity is the result of increased storage of energy in the form of adipose tissue, reducing the quality of daily life, and interfering with longevity. Obesity is also a chronic, low-grade inflammatory disorder. The inflammatory processes affect many organ systems with expanded numbers of immune cells and increased cytokine production. Long-term weight loss is difficult to achieve and maintain. Lifestyle modifications, pharmacologic treatments, and surgical methods are increasingly utilized to ameliorate excess body weight and the comorbidities of obesity, such as diabetes, cardiovascular disease, dyslipidemia, and cancers. Weight loss is also touted to reduce inflammation. Here we review the current literature on human obesity-related systemic and local changes to the immune system and circulating inflammatory mediators. Further, we consider the impact of weight loss to reduce the burden of inflammation, bearing in mind the different methods of weight loss—behavioral change vs. surgical intervention. Impact statement As the prevalence and severity of obesity expand, the negative impact of excess adiposity affects every system of the body. Given that obesity is a subversive attack on the immune system, weight loss should improve inflammation locally and systemically. Weight management strategies like dieting, exercise, and bariatric surgery, thus have the opportunity to reduce the burden of inflammation.

scholarly journals Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Ge Li-Sha ◽  
Zhao Jing-Lin ◽  
Chen Guang-Yi ◽  
Liu Li ◽  
Zhou De-Pu ◽  
...  
Keyword(s):  
Murine Model ◽  
Group Treatment ◽  
Inflammatory Diseases ◽  
Viral Myocarditis ◽  
Coxsackievirus B3 ◽  
Left Ventricular ◽  
Untreated Group ◽  
Myocardial Inflammation ◽  
High Dose ◽  
Dose Dependent

Abstract The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6 and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.

scholarly journals Virus-Host Interactions of Enteroviruses and Parvovirus B19 in Myocarditis

2021 ◽  
Vol 55 (6) ◽  
pp. 679-703
Keyword(s):  
Cell Cycle ◽  
Immune System ◽  
Viral Replication ◽  
Host Cell ◽  
Parvovirus B19 ◽  
Treatment Options ◽  
Viral Myocarditis ◽  
S Phase ◽  
Xenopus Laevis Oocytes ◽  
Replication Sites

Viral diseases are a major threat to modern society and the global health system. It is therefore of utter relevance to understand the way viruses affect the host as a basis to find new treatment solutions. The understanding of viral myocarditis (VMC) is incomplete and effective treatment options are lacking. This review will discuss the mechanism, effects, and treatment options of the most frequent myocarditis-causing viruses namely enteroviruses such as Coxsackievirus B3 (CVB3) and Parvovirus B19 (PVB19) on the human heart. Thereby, we focus on: 1. Viral entry: CVB3 use Coxsackievirus-Adenovirus-Receptor (CAR) and Decay Accelerating Factor (DAF) to enter cardiac myocytes while PVB19 use the receptor globoside (Gb4) to enter cardiac endothelial cells. 2. Immune system responses: The innate immune system mediated by activated cardiac toll-like receptors (TLRs) worsen inflammation in CVB3-infected mouse hearts. Different types of cells of the adaptive immune system are recruited to the site of inflammation that have either protective or adverse effects during VMC. 3. Autophagy: CVB3 evades autophagosomal degradation and misuses the autophasomal pathway for viral replication and release. 4. Viral replication sites: CVB3 promotes the formation of double membrane vesicles (DMVs), which it uses as replication sites. PVB19 uses the host cell nucleus as the replication site and uses the host cell DNA replication system. 5. Cell cycle manipulation: CVB3 attenuates the cell cycle at the G1/S phase, which promotes viral transcription and replication. PVB19 exerts cell cycle arrest in the S phase using its viral endonuclease activity. 6. Regulation of apoptosis: Enteroviruses prevent apoptosis during early stages of infection and promote cell death during later stages by using the viral proteases 2A and 3C, and viroporin 2B. PVB19 promotes apoptosis using the non-structural proteins NS1 and the 11 kDa protein. 7. Energy metabolism: Dysregulation of respiratory chain complex expression, activity and ROS production may be altered in CVB3- and PVB19-mediated myocarditis. 8. Ion channel modulation: CVB3-expression was indicated to alter calcium and potassium currents in Xenopus laevis oocytes and rodent cardiomyocytes. The phospholipase 2-like activity of PVB19 may alter several calcium, potassium and sodium channels. By understanding the general pathophysiological mechanisms of well-studied myocarditis-linked viruses, we might be provided with a guideline to handle other less-studied human viruses.

From peripherally unsubstituted subphthalocyanines with anti-inflammatory activity on macrophages to tri-iodo derivatives with adjuvant and immunostimulatory functions

2019 ◽  
Vol 23 (01n02) ◽  
pp. 56-62 ◽  
Author(s):  
Furkan Ayaz ◽  
Abdulcelil Yuzer ◽  
Mine Ince
Keyword(s):  
Immune System ◽  
Inflammatory Cytokine ◽  
Opposite Effect ◽  
Cytokine Production ◽  
Treatment Options ◽  
Danger Signal ◽  
Inflammatory Cytokine Production ◽  
Different Types ◽  
Anti Inflammatory ◽  
The Impact

In this study we evaluated the impact of iodine substitution on the ability of subphthalocyanines (SubPc) to stimulate or regulate the function of macrophages. Previous studies have focused on the usage of phthalocyanines and their derivatives as treatment options against different types of cancer. In order to obtain better prognosis rates, their possible effects on the immune system cells should be delineated. Unique subphthalocyanines were designed and synthesized by our group and a derivative was generated via iodine substitution. In our study we further tested the effects of the new Subpcs on macrophage cell lines. Macrophages play an important role in the immune system through cytokine production and antigen presentation to other types of the immune system cells. They can define the type and the strength of the immune responses against a particular danger signal. Based on pro-inflammatory cytokine (TNF[Formula: see text], IL1[Formula: see text] and IL6) production levels by macrophages, unsubstituted SubPc had anti-inflammatory properties. However, iodine substitution on the same SubPc created a completely opposite effect since these iodo-substituted SubPc exerted an immunostimulatory effect on macrophages based on significant increases in the pro-inflammatory cytokine production levels compared to the untreated controls. While SubPcs can be used to suppress the pro-inflammatory activities of the macrophages, iodine-substituted SubPcs have potentials to be used as adjuvants and immunostimulatory molecules.

scholarly journals How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer

2021 ◽  
Author(s):  
Jacob Stultz ◽  
Lawrence Fong
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Treatment Options ◽  
Suppressor Cells ◽  
Prostatic Acid Phosphatase ◽  
Clinical Activity ◽  
Immune Resistance ◽  
Tumor Growth Factor ◽  
The Impact

Abstract Background Advanced prostate cancer remains one of the most common and deadly cancers, despite advances in treatment options. Immunotherapy has provided little benefit to a majority of patients, largely due to the immunosuppressive tumor microenvironment that gives rise to inherently “cold tumors”. In this review, we discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies. Methods Databases, including PubMed, Google Scholar, and Cochrane, were searched for articles relevant to the immunology of prostate cancer. We discuss the impact of different types of treatments on the immune system, and potential mechanisms through which prostate cancer evades the immune system. Results The tumor microenvironment associated with prostate cancer is highly immunosuppressive due to (1) the function of regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSCs), (2) the cytokine milieu secreted by tumor stromal cells and fibroblasts, and (3) the production of adenosine via prostatic acid phosphatase. Both adenosine and tumor growth factor beta (TGF-beta) serve as potent immunosuppressive molecules that could also represent potential therapeutic targets. While there have been many immunotherapy trials in prostate cancer, the majority of these trials have targeted a single immunosuppressive mechanism resulting in limited clinical efficacy. Future approaches will require the integration of improved patient selection as well as use of combination therapies to address multiple mechanisms of resistance. Conclusion Prostate cancer inherently gives rise to multiple immunosuppressive mechanisms that have been difficult to overcome with any one immunotherapeutic approach. Enhancing the clinical activity of immunotherapies will require strategic combinations of multiple therapies to address the emerging mechanisms of tumor immune resistance.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

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