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Common to several allergic diseases is the generation of immunoglobulin E (IgE) by plasma cells, when exposed to an innocuous antigen. Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway inflammatory diseases. Asthma is mediated in some patients through eosinophilic inflammatory mechanisms that include allergic sensitization and Th2-mediated immune airway response. COPD, on the other hand is mainly considered a Th1-mediated inflammatory process with neutrophilic predominance or a non-Th2 inflammation, occasionally associated with the presence of airway bacteria or viruses. IgE production appears to play an important role in the development of both COPD and asthma, as it has been associated to respiratory symptoms, lung function, bacterial and viral infections, airway remodeling and bronchial hyperreactivity in both diseases. The aim of this review is to summarize all current data concerning the role of specific and total IgE in COPD and asthma and to highlight similarities and differences in view of possible therapeutic interventions.Background Men who use erectile dysfunction medications for recreational purposes may be at increased risk of becoming psychologically dependent, which in turn could lead to psychogenic-based erectile dysfunction symptoms. Sildenafil has become one of the most commonly prescribed and abused drugs available today. Objectives This study aimed to describe the utilization pattern and associated factors of sildenafil citrate among its users visiting community pharmacies in Gondar, Ethiopia. Methods A facility-based cross-sectional study was conducted from March 20, 2017 to May 10, 2017, among male clients who visited community pharmacies in Gondar town, North West Ethiopia. A self-administered, structured questionnaire was used to collect data from Sildenafil users older than 18 years, that started using the drug (Sildenafil) for at least 6 months before the data collection period. A regression analysis was conducted to determine the association between study variables, and a P-value of less then 0.05 was consideakers to improve the rational use of sildenafil.Objective Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global issue. In addition to managing acute cases, post-COVID-19 persisting symptoms/complaints and different hematological values are of great concern. These have an impact on the patient's well-being and are yet to be evaluated. Therefore, clinical and primary diagnosis based on routine laboratory findings bears high importance during the initial period of COVID-19, especially in regions with fewer diagnostic facilities. Methods Clinical information and associated complaints of the COVID-19 illness confirmed by reverse transcription-polymerase chain reaction (RT-PCR) were collected directly from the patients. Regular follow-ups were obtained on the phone every 2 weeks following recovery for 20 weeks. Initial hematological and radiology findings of the hospitalized patients except for intensive care unit (ICU) and high dependency units (HDUs) and a follow-up evaluation after 4 weeks fo diagnosis and prognosis of COVID-19 illness (p less then 0.05). Conclusion Post-COVID-19 persisting symptoms and the changes in the laboratory values need to be considered with importance and as a routine clinical measure. Post-COVID-19 periodic follow-up for evaluating the patient's physical condition and the biochemical values should be scheduled with care and managed accordingly to prevent future comorbidity in patients with the post-COVID-19 syndrome.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of ACE2 in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of ACE2. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased ACE2 expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.Background The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator. Objective This article aims to demonstrate ATENA's adequate performance and safety for clinical use. Material ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models. Results The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo. Conclusion The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.The interaction between the serine protease urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) focalizes plasminogen activation to cell surfaces, thereby regulating extravascular fibrinolysis, cell adhesion, and migration. uPAR belongs to the Ly6/uPAR (LU) gene superfamily and the high-affinity binding site for uPA is assembled by a dynamic association of its three consecutive LU domains. In most human solid cancers, uPAR is expressed at the invasive areas of the tumor-stromal microenvironment. High levels of uPAR in resected tumors or shed to the plasma of cancer patients are robustly associated with poor prognosis and increased risk of relapse and metastasis. Over the years, a plethora of different strategies to inhibit uPA and uPAR function have been designed and investigated in vitro and in vivo in mouse models, but so far none have been implemented in the clinics. In recent years, uPAR-targeting with the intent of cytotoxic eradication of uPAR-expressing cells have nonetheless gained increasing momentum. Another avenue that is currently being explored is non-invasive imaging with specific uPAR-targeted reporter-molecules containing positron emitting radionuclides or near-infrared (NIR) florescence probes with the overarching aim of being able to (i) localize disease dissemination using positron emission tomography (PET) and (ii) assist fluorescence guided surgery using optical imaging. In this review, we will discuss these advancements with special emphasis on applications using a small 9-mer peptide antagonist that targets uPAR with high affinity.Protein tyrosine phosphatases (PTPs) are modulators of cellular functions such as differentiation, metabolism, migration, and survival. PTPs antagonize tyrosine kinases by removing phosphate moieties from molecular signaling residues, thus inhibiting signal transduction. Two PTPs, SHP-1 and SHP-2 (SH2 domain-containing phosphatases 1 and 2, respectively) and another inhibitory phosphatase, SH2 domain-containing inositol phosphatase (SHIP), are essential for cell function, which is reflected in the defective phenotype of mutant mice. Interestingly, SHP-1, SHP-2, and SHIP mutations are identified in many cases of human leukemia. However, the impact of these phosphatases and their mutations regarding the onset and progression of leukemia is controversial. The ambiguity of the role of these phosphatases imposes challenges on the development of targeting therapies for leukemia. This fundamental problem, confronted by the expanding investigational field of leukemia, will be addressed in this review, which will include a discussion of the molecular mechanisms of SHP-1, SHP-2, and SHIP in normal hematopoiesis and their role in leukemia. Clinical development of leukemic therapies achieved by targeting these phosphatases will be addressed as well.Dehydroepiandrosterone (DHEA) has been revealed to implicate in facilitating osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and inhibiting osteoporosis (OP). However, the underlying molecular mechanism remains largely unknown. Here, we induced osteogenic differentiation of hBMSCs derived from elders using an osteogenic induction medium with or without DHEA. The results showed that osteogenic induction medium (OIM) with DHEA could significantly promote the proliferation and osteogenic differentiation of hBMSCs than OIM alone. By using a Tandem Mass Tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, we screened out 604 differentially expressed proteins (DEPs) with at least one unique peptide were identified [524 OIM vs. complete medium (CM), and 547 OIM+DHEA vs. CM], among these proteins, 467 DEPs were shared in these two different comparative groups. Bioinformatic analysis revealed these DEPs are mainly enriched in metabolic pathways. Interestingly, the expression levels of the DEPs in the metabolic pathways showed a more noticeable change in the OIM+DHEA vs. CM group than OIM vs. CM group. Moreover, the protein-protein interaction (PPI) network analysis revealed that three potential proteins, ATP5B, MT-CYB, and MT-ATP6, involved in energy metabolism, might play a key role in osteogenic differentiation induced by OIM+DHEA. These findings offer a valuable clue for us to better understand the underlying mechanisms involved in osteoblast differentiation of hBMSCs caused by DHEA and assist in applying DHEA in hBMSCs-based therapy for osteogenic regeneration.The cellular slime mold Dictyostelium discoideum is a powerful model organism that can be utilized to investigate human health and disease. Immunology inhibitor One particular strength of Dictyostelium is that it can be utilized for high throughput genetic screens. For many phenotypes, one limitation of utilizing Dictyostelium is that screening can be an arduous and time-consuming process, limiting the genomic depth one can cover. Previously, we utilized a restriction enzyme-mediated integration screen to identify suppressors of polyglutamine aggregation in Dictyostelium. However, due to the time required to perform the screen, we only obtained ∼4% genome coverage. Here we have developed an efficient screening pipeline that couples chemical mutagenesis with the 5-fluoroorotic acid counterselection system to enrich for mutations in genes of interest. Here we describe this new screening methodology and highlight how it can be utilized for other biological systems.
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