Day 2 :
Keynote Forum
Jan-Jong Hung
National Cheng Kung University
Taiwan
Keynote: Role of Ubiquitination in Lung Cancer Progression
Time : 09:45-10:20
Biography:
Professor Jan-Jong Hung has completed his PhD in Life Sciences from National Tsing Hua University, Hsinchu and Post-doctoral studies from Academia Sinica in Taiwan during 1999-2003. At 2009, as a visiting scholar, he came to NIH to do the research with the Dr. Chung-Pin Su. He is the Director of precision instrument of Cheng-Kung University in Taiwan. He has published more than 40 papers related to the lung cancer progression including the initiation and metastasis of lung cancer in reputed journals. Recently he is also to be one of the editors in the ROS Journal.
Abstract:
rnUbiquitin is a critical modifier that regulates the degradation and function of its target protein during post-translational modification. In this study, we found that USP24 is higher expressed in the Cell lines with more malignancy and lung cancer clinical samples of late stage. Studying the single Nucleotide polymorphism of USP24 using genomic DNA of lung cancer patients found an increase in the SNP at 7656C→T. Instead of genomic DNA, using RNA specimens of lung cancer patients to Study the SNP of USP24 appeared that significant increase the ratio of the variant in the 930C→T and 7656T→C compared to the ratio found in the genomic DNA, suggesting that the variant at these two sites is not only found in genomic level but in the process of RNA editing. USP24-930T and USP24-7656C increases expressed level through increasing their RNA stability. Knocking down the level of USP24 increased SUV39h1 level through a decrease in the MDM2 level, thus increased lysine 9 methylation of histone-H3 resulted in preventing lung cancer malignancy. Finally, to study the SNP of USP24 using blood specimen of lung cancer patients also found a higher ratio variant compared to normal population, indicating that the SNP of USP24 at 930C→T and 7656T→C might be as a diagnostic marker for cancer detection. Recently we also found that several cancer-related proteins (Bax, p300, E2F4, TFDP1 and securing) have been proven to be Substrates of USP24 and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting Cellular apoptosis and increasing cellular proliferation. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1 and thus Increases the G1/S transition. The decrease of USP24 in mitosis also reduces the securing level and Promotes separate activation, thereby facilitating the metaphase-anaphase transition. In conclusion, The USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell Cycle to regulate its substrates p300, Bax, E2F4, and securing, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.rn
- Respiratory Tract Infections, Pulmonary Diseases and Therapeutics, Mucosal Immune system in Lung
Session Introduction
Stephan Koelsch
Boehringer Ingelheim in Medicine Consumer Health Care (CHC)
Germany
Title: Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial
Time : 09:45-10:15
Biography:
Stephan Koelsch studied Biology at the University of Mainz until 1994. He then started his PhD studies in Immunology and completed in December 1998. As a Global Senior Medical Advisor at Boehringer Ingelheim, he is responsible for the Consumer Health Care (CHC) Medicine Cough & Cold area. He is author/co-author of more than 20 papers in reputed journals.
Abstract:
Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three clinical trials with common cold patients. To further investigate I C, a fourth randomized, placebo-controlled, double-blind clinical trial was conducted in 200 adult patients with self-diagnosed colds that were confirmed by baseline symptom scores. Respiratory viruses were quantified at baseline and on treatment day 3 or 4. Primary endpoint was the mean total symptom score of 8 cold symptoms on Days 2 to 4. The primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group and also substantiated I-C’s activity against rhinovirus. To observe trends rather than statistically significant outcomes obviously was based on an unexpected low power of the trial. In particular, the proportion of virus-positive patients was smaller than anticipated. Only 23.6% had rhinovirus in contrast to 50-90% in other studies. This low frequency of rhinovirus-positive patients in the ICICC study demonstrates that there may often be a trade-off when the standard design for cold studies is used. When a controlled study tries to recruit patients at the earliest stages of a cold, patients may incorrectly believe they are coming down with a cold, prior to full blown cold symptoms. Hence, the peculiarities of the ICICC study may trigger a discussion among the scientific community about more suitable study designs to investigate common cold treatments.
Li Jiang
The First Affiliated Hospital of Dalian Medical University, China
Title: Artesunate attenuates lung injury in Paraquat-intoxicated rats via the down-regulation of inflammatory cytokines
Time : 10:15-10:45
Biography:
Li Jiang is working in the First Affiliated Hospital of Dalian Medical University, Dalian China and is currently researching on lung injury in Paraquat-intoxicated rats via the down regulation of inflammatory cytokines.
Abstract:
Background & Aims: The present study was designed to analyze the dynamic changes in transforming growth factor beta 1 (TGF-β1), interleukin (IL)-10, and tumor necrosis factor alpha (TNF-α) in paraquat (PQ)-intoxicated rats and to evaluate the effects of artesunate on PQ-induced lung injury. Methods: Sixty healthy male Sprague- Dawley (SD) rats were randomly assigned to the control (n=10), PQ (n=25), and artesunate-treated PQ (n=25) groups. The plasma levels of TGF-β1, IL-10 and TNF-α were measured at 0 (control), 12, 24, 48, and 72 hours after PQ poisoning. The pathological changes in the lung tissues were also examined. Results: Signs of PQ poisoning began to show at 12 hours after PQ administration; the levels of serum TGF-β1, IL-10, and TNF-α were significantly increased (P<0.01), compared with the control group. The effects of artesunate treatment were evident at 12 hours after PQ poisoning and became statistically significant at 48 hours, compared with the control and PQ groups, respectively (P<0.05, P<0.01). Conclusions: The PQ-induced lung injury was attenuated by artesunate treatment. In conclusions: IL-10, TNF-α, and TGF-β1 may play an important role in PQ-induced lung injury, which can be prevented by artesunate treatment.
Marioara Simon
Romanian Pulmonology Society
Romania.
Title: Multimodality endoscopic approach of benign tracheal stenosis BTS
Time : 11:15-11:45
Biography:
Marioara Simon has FCCP, MD, PhD degrees in Pulmonology, Bronchologist and Allergologist. She is the Head of Bronchology and Interventional Pulmonology Department, University Hospital Cluj-Napoca, Romania. She is the President of the Romanian Bronchology Section of the Romanian Pulmonology Society and on Board of WABIP as regent, on Board of EABIP as delegate from Romania. She has a strong interest in the diagnosis and endoscopic therapy of lung cancer. She has participated in EABIP, ERS and WABIP Congresses with presentations and posters and has organized and participated in many bronchological workshops. She has published books (Chronic Interstitial Fibrotic Pneumopathies, Bronchoscopist’s Guide) and more than 130 scientific articles and oral presentations, the majority in the diagnostic bronchoscopy and interventional pulmonology field.
Abstract:
Interventional pulmonology (IP) provides comprehensive care to patients with structural airway disorders. Tracheal stenosis is a potentially life-threatening condition. With the development of interventional pulmonology field in the last 20 years, definitive management of tracheal stenosis using minimally invasive endoscopic methods became a possibility. Benign airway stenoses are frequently seen by the interventional pulmonologist. Endoscopic treatment had been shown to be useful, especially in patients who are deemed high risk and too unwell for reconstructive surgery. Many endoscopic therapeutic interventions can be offered: balloon dilatation, rigid bronchoscopy dilatation, laser or electrosurgery resection and placement of airway stents. We have retrospectively analyzed a series of 27 patients who were referred to our department between 2013-2016 for evaluation and management of symptomatic BTS. The most common condition was postintubation stenosis that develops after prolonged endotracheal intubation. Symptoms varied according to the severity of the stenosis, being the most frequent different degrees of dyspnea, cough and retained secretions. The endoscopic modalities used were: balloon and rigid bronchoscopy dilatation and radial incisions with electrosurgery knife. A stent was placed in two patients. Complications were minor and mostly included restenosis. Over a median follow-up of 30 months, the overall success rate was 85.7%, only three patients being referred to surgery. Conclusion. Tracheobronchial stenoses can be difficult to treat, and patients benefit from a multidisciplinary approach; every case should be discussed within a team of dedicated physicians, including a pulmonary interventionist, an otorhinolaryngologist, and a surgeon, in order to offer the best available solution.
Biography:
Michele Pedicone completed a Masters of Science in Respiratory Care Leadership and Education from Northeastern University in Boston, MA and is currently pursuing a doctoral degree in Global Health Studies at Nova Southeastern University in Fort Lauderdale, FL. She practices respiratory care at the University of Washington Neonatal Intensive Care Unit in Seattle, WA and is an instructor at Seattle Central College also located in Seattle. Ms. Pedicone is active in the Respiratory Care Society of Washington, having served as Vice President and for the American Association for Respiratory Care as a member of the Political Advocacy Team.
Abstract:
Mechanical Ventilation for the very low birth weight infant has traditionally involved either pressure or volume breath types. Modern microprocessor ventilators are capable of delivering hybrid modes which can combine volume and pressure. NAVA takes a unique approach to mechanical ventilation, delivering assistance in proportion to and synchrony with the patients own respiratory efforts. The electrical activity of the diaphragm (EAdi) is captured via an indwelling catheter, this EAdi signal allows for synchronization of the ventilator to the infant's own breathing effort. Synchrony is possible even in the presence of air leak, making this mode a successful choice in the neonate population, both invasively and non invasively. Intubation has potential harmful results for the very low birth weight infant, to include tracheal trauma and infection. In an attempt to minimize these risks, non invasive NAVA has allowed for the synchronous ventilation of very low birth weight infants. A review of the use of non invasive NAVA and case studies from a Level IV Neonatal Intensive Care Unit (NICU) will be presented.
- Prevention of Lung Disorders, Prevention & Control of Respiratory diseases, Lung disorder
Session Introduction
Hanski Leena
University of Helsinki
Finland
Title: Impact of β2, 2-amino acids, a novel class of Chlamydia pneumoniae inhibitors, on bronchial epithelium VEGF production
Time : 11:45-12:15
Biography:
Hanski L has completed her PhD in 2010 from University of Helsinki and Docentship in Pharmaceutical Biology from Åbo Akademi University (Turku, Finland) in 2013. She is the chief researcher of Chlamydia research team and acts as the university lecturer responsible for teaching in Pharmaceutical Microbiology in Faculty of Pharmacy, University of Helsinki. The main focus of her research is in the therapy approaches on C. pneumoniae and RNA viruses and has published 25 scientific papers, including four invited reviews.
Abstract:
The obligate intracellular bacterium Chlamydia pneumoniae is a ubiquitous human pathogen responsible for 5-10% of community-acquired pneumoniae cases and a variety of milder upper and lower respiratory tract infections. Owing to its propensity to persistence, C. pneumonae infections are associated with treatment failures, and the presence of the bacterium in the respiratory tract has been shown to induce the production of various proinflammatory cytokines and growth factors like vascular endothelial growth factor VEGF. The chronic inflammation induced by C. pneumoniae links the bacterium to asthma and other inflammatory diseases. We have recently described the ability of amphipathic β2, 2-amino acid derivatives, developed from cationic antimicrobial peptides, to target C. pneumoniae on both in intracellular and extracellular forms of the bacterium, indicating that the eradicative effect of these agents on C. pneumoniae is not dependent on its replication. In the current work, we report on the ability of the β2,2-amino acid derivatives to suppress VEGF production induced by C. pneumoniae in bronchial epithelial cells. According to our data, the C. pneumoniae clinical isolate K7 induced significant VEGF production in BEAS-2B cells, and both studied β2,2-amino acid derivatives A1 and A2 suppressed the VEGF production at concentrations 5 µM and below. The derivatives were more effective in this respect than azithromycin, a gold standard for treating chlamydial infections. Regarding the known role of VEGF in the pathophysiology of asthma and related diseases, these results illustrate the potential of these non-conventional antichlamydial agents in suppressing C. pneumoniae and the infection consequences in bronchial epithelium
Jing Liu
The Army General Hospital of the Chinese, China
Title: The lung ultrasonography for the diagnosis of neonatal lung diseases
Time : 12:15-12:45
Biography:
Jing Liu is the Leader and Director of the neonatal intensive care unit of Bayi Children's Hospital, the vice president of Bayi Children's Hospital Affiliated to the Army General Hospital of the Chinese PLA. His academic positions include Associate Chairman of Committee of PLA Academy of Pediatrics, Associate Chairman of Chinese Neonatologist Association and Editorial member of 20 Chinese and English Journals. He has published over 260 papers as a first author, 10 books and Chapters in Books. He is good at neonatal brain ultrasound and neonatal lung ultrasound, his research work has been supported by China Natural Science Foundation etc., and has won 10 awards for science and technology of the government of China.
Abstract:
Various lung diseases are the most common conditions and the leading cause of hospital admission and death in newborns. Generally, the differential diagnosis of lung diseases primarily relied on clinical manifestations, arterial blood gas analysis, conventional chest X-ray and computed tomography (CT) scans, the lung ultrasound is not typically applied when diagnosed neonatal lung diseases. However, chest X-ray and CT scans suffer from obvious limitations, while Lung ultrasonography (LUS) has become an important method for diagnostic examination and monitoring of lung disease. Many kinds of lung diseases, such as respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, meconium aspiration syndrome, atelectasis and pneumothorax were diagnosed by chest x-ray or CT scan in the past, but can now easily be diagnosed with lung ultrasound. Lung ultrasound has many advantages over X-ray and CT scan including accuracy, reliability, low-cost and simplicity, as well as the fact that ultrasound incurs no risk of radiation damage. It is therefore feasible and convenient to perform at the bedside in a neonatal ward. This topic will focuses on the features of LUS in neonatal lung disease mentioned above and differentiating long-term oxygen dependence in premature infants; and thus to improve the application of ultrasound in pediatric respiratory diseases.
Camille Lowman
Tacoma Community College
USA
Title: Therapist Driven Protocols Revisited
Time : 12:45-13:15
Biography:
Camille Lowman has been the Director of Clinical Education, and Tenured Professor, for Tacoma Community College’s Respiratory Care Program since 2007. Prior to accepting the position at TCC, Camille spent 28 years as a staff respiratory therapist in acute care performing mostly critical care respiratory care in adult medicine, pediatrics and neontal. She served on a neonatal air/ground transport team for 2 years, and on a Pediatric Critical Care Ground Transport Team for 6 years. She established and managed a Sleep Medicine Center, managed the Respiratory Diagnostics Department and Nutrition Deparment in a hospital for 6 years. She received her Respiratory Therapy Degree from Tacoma Community College in 1985 and her Bachelor of Science in Business Administration from Colorado Technical University in 2009. She is now pursuing a Master of Public Health from Benedictine University in Illinois.
Abstract:
Drastic changes in medical practice and payment for services in the United States has prompted a close look at how Respiratory Care is being delivered and how best to move forward in the ever changing invironment. In fact, in some departments, routine care has been given over to nursing services while the Respiratory Therapist remains involved in the care of only the sickest patients. However, new laws being enacted have placed Chronic Obstructive Pulmonary Disease as one of the diagnoses that will see hospitals “fined” for readmissions also known as “bounce backs”. While education of these patients will become extremely important in the care process, additionally, the involvment of the Respiratory Therapist at the bedside will continue to prove imperative in assuring that treatment progresses optimally while they are inpatients in the acute care facility. This will include Respiratory Care Departments “taking back” therapy that has been previously “given away” to other departments. Therapist Driven Protocols, having been introduced in the late 1990’s in the United States, empower the Respiratory Therapist to direct therapy based upon the patient’s need after the physician writes an order for “Respiratory Care to assess and treat”. The therapist then follows an algorrhythm that guides in choosing the proper therapy (through protocols established by department medical directors), frequency and medications based upon severity of patient illness and symptoms. Studies have shown that patients respond more quickly to treatment when a therapist is directly involved in guiding the care. Therapist involvment at all levels of care is essential to creating positive outcomes for these patients.
Daneshmehr, Mohammad Ali
Iran University of Medical Sciences, Iran
Title: International Conference on Travel Medicine, Vaccines & Therapeutics
Time : 14:45-15:15
Biography:
Dr. Mohammad Ali Daneshmehr has studied pharmacy at Tehran University of Medical Sciences (TUMS), and graduated in 1990. He started his career in Shahid Beheshti University of Medical Sciences (SBMU) as an instructor. In 1993 he pursued his studies in University of Manchester, UK in medicinal chemistry and got PhD (2001) on ligands in DNA minor groove. He has been working since, in different parts of Iran as founder of a number of pharmacy schools including Hamadan (UMSHA), Kermanshah (KUMS) and currently Iran University of medical Sciences (IUMS). Fields of interests includes natural products as lead compounds to find new drugs.
Abstract:
Acute respiratory tract infections account for millions of lost effective work or school days, healthcare clinic visits, antibiotic prescriptions, hospital admissions and eventually morbidity or even mortalities. International tourism including religious pilgrimage to overcrowded destinations considerably increases the chance for dissemination of such contaminations. As an example, Hajj is a world wide ceremony that can affect every country with Muslim sub-population regarding surge of multi-microbial and drug resistant respiratory tract infections. Therefore disease prevention in the involved societies would be highly life and cost saving. Besides use of common antibiotics that has major drawbacks, natural immune boosters are viable and accredited options in this field. Echinacea supplements are well-known for immune-modulation and anti-flu effects. They have all characteristics that recommended by CDC to fight flu: immune augmentation, evidence-based preventive value and anti-viral (microbial) properties without promoting any resistance or life-threatening adverse reactions. Echinacea vastly grows in different geographical teritories, is reasonably affordable and easily accessible almost all over the world just like in Iran. As we published in a recent review article, there is a huge amount of evidence that shows promising results for Echinacea in both prevention and treatment of respiratory tract infections especially in high risk populations and would be potentially useful in susceptible travelers. There will be a great opportunity to prevent respiratory tract infections related to international gatherings and their infectious adverse consequenses with standard protocls for supplementation of natural products like Echinacea after adequate examinations via goal-directed clinical trials.
Mice Min-Chao Duan
Eighth People's Hospital of Nanning, China
Title: Th17 cell enhances CD8 T-cell cytotoxicity via IL-21 production in Emphysema
Time : 15:15-15:45
Biography:
Min-Chao Duan is working in Department of Respiratory Medicine, at the Eighth People's Hospital of Nanning, China. He is researching on non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC.
Abstract:
Emphysema is a T-cell mediated autoimmune disease caused predominantly by cigarette smoking. Th17 cells and related cytokines may contribute to this disorder. However, the possible implication of Th17 cells in regulating inflammatory response in emphysema remains to be elucidated. In the current study, we tested the protein levels of IL-17 and IL-21 in peripheral blood and lung tissues from cigarette-smoke- (CS-) exposed mice and air-exposed mice, analyzed the frequencies of CD4+IL-17+(Th17) cells, IL-21+Th17 cells, and CD8+IL-21R+ T cells in peripheral blood and lung tissues of mice, and their relationship with emphysematous lesions, and explored the impact of IL-21 on cytotoxic CD8+ T cells function in vitro. It was found that the frequencies of Th17, IL-21+Th17, and CD8+IL-21R+ T cells and the levels of IL-17 and IL-21 of CS-exposed mice were much higher than those of the air-exposed mice and correlated with emphysematous lesions. Additionally, the number of IL-21+Th17 cells positively correlated with the number of CD8+IL-21R+ T cells. The in vitro experiments showed that IL-21 significantly augmented the secretion of performing and granzyme B in CD8+ T cells from CS-exposed mice. These data indirectly provide evidence that Th17 cells could be involved in the control of the local and system inflammatory response in emphysema by regulating CD8+ cytotoxic T-cell function.
Hanna Schmidt
Ulm University
Germany
Title: Interleukin-13 impairs barrier function of human airway epithelia by inducing ubiquitination and internalization of tight junction proteins
Time : 15:45-16:15
Biography:
Hanna Schmidt is 25 years old and has been studying medicine since 2010 at Ulm University (Germany). From 2013 to 2016 she did her doctorate in the Institute of General Physiology. Her thesis is currently under revision. She is working in the field of lung epithelial physiology and her research focuses on water and ion transport and epithelial barrier function.
Abstract:
The airway epithelium forms the first defense line against airborne pathogens. Its tightness depends on tight junction (TJ) complexes. Disturbances of TJ result in epithelial barrier damage, facilitate pathogen invasion and thereby aggravate chronic inflammatory lung diseases. The cytokine interleukin-13 (IL-13) has been shown to play a pivotal role in inflammatory lung diseases as asthma or COPD. Whereas increased mucus production is a well described IL-13 effect, its impact on barrier function is hardly elaborated. Therefore, our study aimed on the effect of IL-13 on barrier function and TJ of airway epithelia. IL-13 exposure of primary human tracheal epithelial cells (hTEpC) cultivated as air-liquid-interface reduced transepithelial electrical resistance and increased permeability for sodium fluorescein. RT-PCR experiments revealed reduced mRNA transcript levels of the TJ proteins claudin 8, 9 and 16 and upregulation of the ubiquitin E2 ligase (UBE2Z). Immuncytochemical experiments revealed a reduced apico-lateral localization and an intracellular accumulation of TJ proteins in IL-13 treated hTEpC. By contrast, the lateral localization of the adherens junction protein E-cadherin remained unaffected by IL-13. Janus kinase inhibitors abolished IL-13 effects. Proximity ligation assays demonstrated ubiquitination of TJ proteins as well as interaction of ZO 1 and several claudins with the ubiquitin conjugating enzyme UBE2Z. Our results demonstrate, that IL-13 impairs airway epithelial barrier by internalization of TJ proteins via an ubiquitin dependent mechanism. Therefore, IL-13 signaling could be a promising therapeutic target to prevent epithelial dysfunction in inflammatory lung diseases.Supported by Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (Az: 32-7533.-6-10/15/5) to OW