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Background:SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2), the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity. Objective: In this pilot study we followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination. Methods: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days ) and dexamethasone (100mg/day ). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs. Results: Baseline sACE2 levels were lower in severe (p=0.0005) and moderate (p=0.0022) patients than in patients with mild COVID-19 and in HC (p=0.0023 and p=0.0012 respectively). Serum sACE2 levels increased in patients with severe disease recovered over time compared with moderate (p=0.0021) and severe (p=0.0411) COVID-19 subjects at baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes. Funding: IMA is financially supported by the Welcome Trust (093080/Z/10/Z), the EPSRC (EP/T003189/1), and the Community Jameel Imperial College COVID-19 Excellence Fund (G26290) and by the UK MRC (MR/T010371/1). SM is supported by EU project 853850. Declaration of Interests: The authors declare that there is no conflict of interest to this article. Ethics Approval Statement: The study was approved by the institutional ethics board of the Masih Daneshvari Hospital (Ethics number SBMU.NRITLD.REC.1399.226).

BACKGROUND: Globally, lung cancer represents a major cause of cancer-related deaths. The regulation of gene expression is modulated by small noncoding RNAs called miRNAs that can act as both tumor suppressors and oncogenes. The maturation, expression and binding to target mRNAs is affected by single nucleotide polymorphisms (SNPs) in miRNA genomic regions thereby contributing to cancer susceptibility. SNPs Rs11614913 in miR196a and Rs3746444 in miR-499 are implicated in the development of cancers such as non-small cell lung cancer (NSCLC) in non-Arabic subjects. MATERIALS AND METHODS: A small cohort of 204 participants including 104 lung cancer patients and 100 non-cancer controls subjects were enrolled into the study. The allele frequencies were determined by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) and their correlation with lung cancer risk was determined. RESULTS: The miR-196a rs11614913 polymorphism increased the risk of NSCLC (CC vs. TT+TC: OR= 2.26, 95%CI= 1.28 - 3.98, P= 0.0046) in a dominant genetic model. No statistically significant association was found between the miR-499 rs37464444 polymorphism and NSCLC. CONCLUSION: The rs11614913 polymorphism in miR-196a, but not the miR-499 rs37464444 polymorphism, increased the risk of NSCLC. Further studies with larger sample sizes in correlation with functional outcomes at the cellular level should be undertaken.

In late December 2019 a viral pneumonia with an unknown agent was reported in Wuhan, China. A novel coronavirus was identified as the causative agent. Because of the human-to-human transmission and rapid spread; coronavirus disease 2019 (COVID-19) has rapidly increased to an epidemic scale and poses a severe threat to human health; it has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). This review aims to summarize the recent research progress of COVID-2019 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 ( SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus(MERS-CoV.)

Background: Myeloid-derived suppressor cells (MDSC) are categorized as granulocytic (G-MDSCs) and monocytic (M-MDSCs) and their expansion play a role in cancer progression. Recruitment to the cancer site depends upon the presence of a chemoattractant. We aimed to investigate the presence of MDSC subtypes and of interleukin-8 (CXCL-8) in the peripheral blood in lung cancer subtypes including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Materials and Methods: Peripheral blood samples of 26 NSCLC patients, 18 SCLC patients, and 8 healthy control donors (HDs) were harvested and the surface expression of CD14, CD15, CD11b, and HLA-DR on MDSCs was measured using flow cytometry. The level of serum CXCL8 was measured by the ELISA method. Results: The frequency of circulating M-MDSCs was significantly higher in patients with NSCLC than in SCLC and HDs. In contrast, there was no statistical difference concerning the frequency of circulating G-MDSCs between the three groups. The concentration of CXCL-8 was significantly higher in the NSCLC and SCLC patients than in HD control with no significant difference between NSCLC and SCLC groups. There was no correlation between serum CXCL8 and G-MDSC levels. Conclusion: Our data confirm a higher frequency of circulating M-MDSCs, but not G-MDSCs, in the blood of those suffering from NSCLC but not for SCLC cases. Measuring MDSC subtypes and serum chemotactic factors may have implications for the differential diagnosis of NSCLC.

Sarcoidosis is a multi-organ disease and is characterized by sarcoidal noncaseating granuloma comprised of T-helper/inducer (CD4+) lymphocytes and scant cytotoxic (CD8+) T-lymphocytes. CD4+:CD8+ T-cell elevated ratio is a characteristic diagnostic parameter for sarcoidosis. This is the first report from Iran evaluating the CD4:CD8 ratio capability in differentiating pulmonary sarcoidosis from other interstitial lung diseases (ILDs) on a large cohort. Fifty pulmonary sarcoidosis patients and 50 non-sarcoidosis interstitial lung diseases (nsILDs) patients were included in the current study. Bronchoalveolar lavage (BAL) was performed using flexible fiberoptic bronchoscopy and flow cytometer. Non-sarcoidosis group was established by 50 components that were classified into eight subgroups. Fifty-two percent of sarcoidosis patients and 62% of non-sarcoidosis interstitial lung disease patients had normal spirometric results. The CD4/CD8 ratio was significantly higher in sarcoidosis than in non-sarcoidosis interstitial lung diseases (p < 0.001). The CD4/CD8 ratio was found to be > 3.5 in 33.3%, 2.5-3.5 in 7.1%, 1.5-2.5 in 20.2% and < 1.5 in 39.4% of the entire study population. The best cut off point was 1.1 with the sensitivity of 92% and specificity of 80% for distinguishing sarcoidosis from other interstitial lung diseases. Performing bronchoalveolar lavage as the safe and rapid first step confirms the diagnosis of sarcoidosis in 92% of cases (current study sensitivity). Hence, performing an invasive procedure was required in a few patients only. Bronchoalveolar lavage flow cytometry in the assessment of clinical and radiological findings supplies an appropriate diagnostic adjunct for discriminating sarcoidosis from non-sarcoidosis interstitial lung diseases.

Cystic Fibrosis (CF) is the most common lethal autosomal recessive disease that affects many organs including, lung, pancreas and liver. Cystic fibrosis is a monogenic disease and occurs in the white Caucasians. Massive neutrophil granulocyte influx in the airways is one of the characteristics of CF. Extracellular Vesicles (EVs), microvesicles, and exosomes are vesicles released from cells into extracellular space of the body and are able to influence other cells by different methods. They have an important role in the intracellular communication by transferring information between donor and recipients cells. Granulocytes are known as the main source of microparticles in the CF patients. Microparticles derived from neutrophils are associated with the extensive neutrophil influx into airways and aggregation at the epithelial surface of the CF patient's respiratory tract. Exosomes are found in almost all body fluids, such as urine, sputum, Bronchoalveolar Lavage (BAL), milk, Cerebrospinal Fluid (CSF), plasma and sputum. Examination of exosomes derived from CF patients may be helpful in the characterization of pathogenesis of disease in detail. In this mini review, we have summarized the role of microparticles and exosomes in pathogenesis of CF and finally discussed the feasibility of this particle in treatment approaches.

Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation.

Introduction: Tuberculosis remains a major threat to human health. Understanding the strategies mycobacterium takes to overcome immune defense is important to control the infection. miRNAs are master regulators of most pathways in the human body. Infection with mycobacterium impacts upon host metabolic pathways to obtain the nutrition for its intracellular survival. In this study, we aimed to investigate the effect of BCG infection on the expression of three miRNAs (miR-1224, -484 and -425), which have been previously demonstrated to be important in infection and metabolic pathways. Methods: Blood-derived monocyte derived macrophage (MDM) cultures were prepared and infected with BCG at a multiplicity of infection (MOI) =10 or left uninfected as a control. 72h post-infection, the cultured cells were subjected to RNA extraction, cDNA synthesis and real-time PCR. Expression levels miRNAs were normalized to the levels of U6 snRNA (Rnu6) using the 2–ΔΔCt method Results: Infection with BCG resulted in a highly significant increase in miR-1224 expression (24.4±3.8-fold induction) in human MDMs. The induction of miR-484 (1.8±0.3-fold increase) and of miR-425 (1.2±0.2-fold increase) was less increased compared to miR-1224. Discussion: Mycobacterium tolerate an hostile microenvironment by escaping from lysosomal degradation and providing a lipid-rich niche by trigger with and re-pattering host metabolism. These data highlight the potential importance of miR-1224 in the host metabolic response to TB infection and a possible role of miR-484 in the reprogramming of metabolic pathways in infected cells. Further work is required to determine whether these miRNAs may also be useful as biomarkers for the diagnosis or monitoring of treatment in TB patients. Conclusion: This study Highlighted the potential roles of miRNAs in host immunologic responses upon mycobacterium infection. Further work is required to determine whether these miRNAs may also be useful as biomarkers for the diagnosis or monitoring of treatment in TB patients.

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil. NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors. Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections.

miRNAs contribute to a variety of essential biological processes including development, proliferation, differentiation, and apoptosis. Circulating microRNAs are very stable and have shown potential as biomarkers of cardiovascular disease. microRNA-208b expression was increased in the blood of patients with acute myocardial infarction (AMI) and has been proposed as a biomarker for early diagnosis. In this pilot study, we investigate the potential of circulating miR-208b as a prognostic biomarker of 6-month survival in AMI patients. Methods. Plasma samples from 21 patients and 8 age- and gender-matched healthy adults were collected, and circulating levels of miR-208b were detected using quantitative real-time PCR. Results. miR-208b levels were higher in healthy control subjects (9.6-fold; ). Within the AMI patients, the levels of miR-208b were significantly lower in the survivor versus nonsurvivor group (fold change = 6.51 and 14.1, resp.; ). The Kaplan-Meier curve revealed that the 6-month survival time was significantly higher among AMI patients with a relative expression of miR-208b lower than 12.38. The hazard ratio (HR) for the relative expression of miR-208b (

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil. NTM cause a variety of diseases in human in which mainly lung is involved. A predisposition to pulmonary NTM is seen in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases, and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as it can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in HIV-infected patients or those with severely compromised immune system. NTM is also reported in many subjects without any known risk factor. Although the recent advances in imaging and microbiologic techniques including gene sequencing has provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections.

Background : Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural - based treatments. Toll - like receptors (TLRs) play an important role in evoking innate immunity agains t cancer cells. Zymosan, a known TLR - 2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae - derived z ymosan - modulated skin melanoma progression by regulation of TLR - 2 expression in peritoneal macrophages and serum TNF -  level. Methods: Male C57BL/6 mice were divided into four groups: i) zymosan - treated (Z), ii) Melanoma - bearing mice (M), iii) Melanoma - bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10  g) daily for 4 consecutive days. Mice were CO 2 - euthanized and serum TNF - α level, TLR - 2 expression in peritoneal macrophages and tumor gro wth measured. Splenocytes were treated ex - vivo with zymosan to determine viability and proliferation. Results: Tumor weight significantly decreased following therapeutic dosing with zymosan ( P

Different phenotypes of asthma from mild to severe are categorized based on diverse clinical features. A guideline for the recognition and treatment of asthma has been provided by Global Initiative for Asthma (GINA). To control symptoms and prevent asthma exacerbation in most patients combinational therapy with inhaled corticosteroids (ICS) and a long acting B2-adrenreceptor agonist (LABA) are recommended. Understanding asthma phenotypes would be helpful to improve asthma diagnosis and treatment. The aim of this study was to verify glucocorticoid receptor glcococorticoid receptor (GR) nuclear translocation in CD4 T cells treated with fluticasone furoate (FF), vilanterol (V) and FF/V combination in severe asthmatic patients compare to patients with moderate asthma and healthy controls using Immunocytochemistry (ICC). After taking blood and separating PBMCs from each subject, CD4 T cells were isolated from PBMCs using CD4+ T cell isolation kit. Isolated CD4 T cells were cultured in presence of FF, V and FF/V combination for 1 hour and after cytocentrifugation, cells were incubated with anti GR-antibody and subsequently stained with FITC bound secondary antibody and GR nuclear translocation was observed under microscope. The results showed significant increasing in GR nuclear translocation in treated CD4 T cells from patients with moderate asthma and controls compare to those severe asthmatic patients, along with treating cells with FF/V combination no significant GR nuclear translocation was observed compare to that of using mono treatment of cells with FF and V. Based on our findings, it can be concluded different mechanisms are responsible for severe asthma and moderate asthma.

Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities.

Tuberculosis (TB) and tobacco use are two major alarming global health issues posing immense threats to human populations. Mycobacterium tuberculosis (MTB) by activation of macrophages could induce the sequences of cells activation and releases of inflammatory cytokines such as CXCL-8, Il-12 and TNF-α which in turn induces the immune system network. However no information is available on other activity of cells by MTB and smoking. In the current study we aimed to investigate the serum levels TNF-a, CXCL-8 and phagocytosis capacity in tuberculosis patients with and without smoking. 103 subjects entered the study including 61 new diagnosed pulmonary TB patients (23 smokers and 38 nonsmokers) and 42 control healthy subjects. The phagocytosis of fluorescein isothiocyanate dextran (FITC-dextran) in blood monocytes/macrophages through flowcytometry was assessed. Serum levels of TNF-a and CXCL-8 were analyzed by ELISA methods. A lower percentage of cells from TB patients who smoked [50.29% (43.4-57.2), p

Innate lymphoid cells (ILCs) are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th)1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages.Three types of ILCs (ILC1, 2 & 3) have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK) cells and interferon (IFN)-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis.There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD). Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases.In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD.

Tuberculosis (TB) has previously been linked to acute respiratory distress syndrome (ARDS). Here this study investigates the link between inflammation and TB in ARDS by measuring inflammatory cytokine and chemokine levels in bronchoalveolar lavage (BAL) from 90 patients with TB or ARDS alone and in patients with TB-induced ARDS (ARDS + TB). BAL was collected by fiber-optic bronchoscopy, and the concentrations of interleukin (IL)-6, CXCL8, TNF α and IL-1β were measured by ELISA. CXCL8 levels in BAL were significantly higher in the ARDS + TB group compared with TB and ARDS alone groups. Disease severity in the ARDS + TB group as determined by Murray score correlated with BAL CXCL8 and neutrophils, but not with IL-6, IL-1β and TNF α concentrations. In addition, CXCL8 levels and neutrophils were increased in non-miliary TB versus miliary TB. This difference in CXCL8 was lost in the presence of ARDS. It was concluded from this study that CXCL8 may play an important role in the pathogenesis of this form of ARDS. This further suggests that CXCL8 inhibitors or blockers may be useful to control the onset and/or development of these combined diseases.

Our understanding of tuberculosis (TB) pathology and immunology has become extensively deeper and more refined since the identification of Mycobacterium tuberculosis (MTB) as the etiologic agent of disease by Dr. Robert Koch in 1882. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. TB, caused by MTB, is a major health problem in world, with 10 million new cases diagnosed each year. Innate immunity is shown playing an important role in the host defense against the MTB, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of MTB, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), and nod-like receptors (NLRs). Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down streams, proteins play the most prominent roles in the initiation of the immune response against MTB. Beside of TLRs signaling, recently the activation of inflammasome pathway in the pathogenesis of TB much appreciated. Knowledge about these signaling pathways is crucial for understanding the pathophysiology of TB, on one hand, and for the development of novel strategies of vaccination and treatment such as immunotherapy on the other. Given the critical role of TLRs/inflammasome signaling in innate immunity and initiation of the appropriate adaptive response, the regulation of these pathways is likely to be an important determinant of the clinical outcome of MTB infection. In this review paper we focused on the immune response, which is the recognition of MTB by inflammatory innate immune cells following infection.

Tobacco smoke is the main factor in the etiology of lung emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' lungs over time and induces tissue damage. Objectives: To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced lung emphysema in mice and increases IL-8 release by human monocytes. Methods: C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight. Results: Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce lung emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release. Conclusions: Humic acid deposition in the lungs potentiates the development of cigarette smoke-induced interstitial inflammation and lung emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study emphysema and may direct the search for new therapeutic approaches. © 2011 Elsevier Ltd.