Search results for: lung surfactant

Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Ogbonnaya Nwokoro, Florence O. Anya

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Nutritional factors relating to the production of linamarase from Lactobacillus delbrueckii NRRL B–763 were investigated. The microorganism was cultivated in a medium containing 1% linamarin. Enzyme was produced using a variety of carbon substrates but the highest enzyme activity was detected in the presence of salicin (522 U/ml) after 48 h while the lowest yield was observed with CM cellulose (38 U/ml) after 72 h. Enzyme was not produced in the presence of cellobiose. Among a variety of nitrogen substrates tested, peptone supported maximum enzyme production (412 U/ml) after 48 h. Lowest enzyme production was observed with urea (40 U/ml). Organic nitrogen substrates generally supported higher enzyme productivity than inorganic nitrogen substrates. Enzyme activity was observed in the presence of Mn2+ (% relative activity = 216) while Hg2+ was inhibitory (% relative activity = 28). Locally-formulated media were comparable to MRS broth in supporting linamarase production by the bacterium. Higher enzyme activity was produced in media with surfactant than in media without surfactant. The enzyme may be useful in enhanced degradation of cassava cyanide.

Keywords: linamarase, locally formulated media, carbon substrates, nitrogen substrates, metal ions

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Authors: C. Mendoza Ramírez, M. Gambús Ordaz, R. Mercado Ojeda.

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Chemical solutions flooding with surfactants, based on their property of reducing the interfacial tension between crude oil and water, is a potential application of chemical enhanced oil recovery (CEOR), however, the high-rate retention of surfactants associated with adsorption in the porous medium and the complexity of the mineralogical composition of the reservoir rock generates a limitation in the efficiency of displacement of crude oil. This study evaluates the effect of the concentration of a mixture of anionic-non-ionic surfactants with silica nanoparticles, in a rock sample composed of 25.14% clay minerals of the kaolinite, chlorite, halloysite and montmorillonite type, according to the results of X-Ray Diffraction analysis and Scanning Electron Spectrometry (XRD and SEM, respectively). The amount of the surfactant mixture adsorbed on the clay rock minerals was analyzed from the construction of its calibration curve and the 4-Region Isotherm Model in a UV-Visible spectroscopy. The adsorption rate of the surfactant in the clay rock averages 32% across all concentrations, influenced by the presence of the surface area of the substrate with a value of 1.6 m2/g and by the mineralogical composition of the clay that increases the cation exchange capacity (CEC). In addition, on Region I and II a final concentration measurement is not evident in the UV-VIS, due to its ionic nature, its high affinity with the clay rock and its low concentration. Finally, for potential CEOR applications, the adsorption of these mixed surfactant systems is considered due to their industrial relevance and it is concluded that it is possible to use concentrations in Region III and IV; initially the adsorption has an increasing slope and then reaches zero in the equilibrium where interfacial tension values are reached in the order of x10-1 mN/m.

Keywords: anionic–nonionic surfactants, clay rock, adsorption, 4-region isotherm model, cation exchange capacity, critical micelle concentration, enhanced oil recovery

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Authors: Wahyu Purnama Putra, Artono Isharanto

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Thoracic trauma is trauma that hits the thoracic wall or intrathoracic organs, either due to blunt trauma or sharp trauma. Thoracic trauma often causes impaired ventilation-perfusion due to damage to the lung parenchyma. This results in impaired tissue oxygenation, which is one of the causes of acute respiratory distress syndrome (ARDS). These changes are caused by the release of pro-inflammatory mediators, plasmatic proteins, and proteases into the alveolar space associated with ongoing edema, as well as oxidative products that ultimately result in severe inhibition of the surfactant system. This study aims to predict the incidence of acute respiratory distress syndrome (ARDS) through human neutrophil elastase levels. This study examines the relationship between plasma elastase levels as a predictor of the incidence of ARDS in thoracic trauma patients in Malang. This study is an observational cohort study. Data analysis uses the Pearson correlation test and ROC curve (receiver operating characteristic curve). It can be concluded that there is a significant (p= 0.000, r= -0.988) relationship between elastase levels and BGA-3. If the value of elastase levels is limited to 23.79 ± 3.95, the patient will experience mild ARDS. While if the value of elastase levels is limited to 57.68 ± 18.55, in the future, the patient will experience moderate ARDS. Meanwhile, if the elastase level is between 107.85 ± 5.04, the patient will likely experience severe ARDS. Neutrophil elastase levels correlate with the degree of severity of ARDS incidence.

Keywords: ARDS, human neutrophil elastase, severity, thoracic trauma

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Authors: Rene A. Amadore Jr., Ramar John Bangayan, Therese Eileen L. Natividad

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This is a case of a 59-year-old female who presented with a two-year history of heliotrope rash, Gottron's papules, shawl sign, V-neck sign, and muscle weakness. She was previously managed as a case of systemic lupus erythematosus, who initially responded to unrecalled corticosteroids. She was, however, admitted due to a one-month progressively enlarging sacral mass, which eventually turned out to be an abscess. While the abscess was being treated, her autoimmune condition was worked up, and she was then managed as a case of clinically amyopathic dermatomyositis (CADM) with interstitial lung disease (ILD). She received corticosteroids and underwent the first cycle of cyclophosphamide infusion prior to discharge.

Keywords: clinically amyopathic dermatomyositis, interstitial lung disease, corticosteroids, sacral abscess

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Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

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Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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Authors: Hsin-Yi Huang

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This study mainly discussed the disease-induced and surgery-induced physical, psychological, and spiritual issues faced by a patient who suffered from emphysema and respiratory failure and had underwent a right-lung transplantation surgery. Nursing care was provided from May 21 to May 29. Based on the observations, interviews, physical examinations, and evaluations that were carried out using Roy’s adaptation model, the following nursing issues were identified: risk of infection, lack of knowledge, and anxiety. Active care was provided and a good nursing relationship with the patient and the patient’s family was established. The four strategies of Bandura’s self-efficacy theory (self-transcendence, vicarious experience, verbal persuasion, and biofeedback) were employed. Instructions for the appropriate rehabilitation exercises were given, immunosuppressant concentration was monitored, and special measures were taken to prevent infection. The patient was encouraged to express feelings and was provided with sufficient information to alleviate anxiety. With assistance from nursing personnel and the medical team, the patient was successfully discharged from the hospital and thereafter embarked on the path of postoperative recovery. The patient learned about the importance of home self-care and regular follow-up outpatient visits, and patient management was implemented for discharge preparation services. This nursing case study may serve as a reference to nurses managing similar cases in future.

Keywords: anxiety, lung transplantation, Roy's adaptation model, self-efficacy theory

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi

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Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

Keywords: chemokine, HIV/AIDS, IP-10 urine, tuberculosis

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Authors: A. Asselah, A. Khalfi, M. A.Toumi, A.Tazerouti

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The study of the corrosion inhibition of a standard carbon steel "API 5L grade X70" by two biodegradable anionic surfactants derived from fatty acids by photo sulfochlorination, called sodium lauryl methyl ester sulfonates and sodium palmityl methyl ester sulfonates was carried. A solution at 2.5 g/l NaCl saturated with carbon dioxide is used as a corrosive medium. The gravimetric and electrochemical technics (stationary and transient) were used in order to quantify the rate of corrosion and to evaluate the electrochemical inhibition efficiency, thus the nature of the mode of action of the inhibitor, in addition to a surface characterization by scanning electron microscopy (MEB) coupled to energy dispersive X-ray spectroscopy (EDX). The variation of the concentration and the temperature were examined, and the mode of adsorption of these inhibitors on the surface of the metal was established by assigning it the appropriate isotherm and determining the corresponding thermodynamic parameters. The MEB-EDX allowed the visualization of good adhesion of the protective film formed by the surfactants to the surface of the steel. The corrosion inhibition was evaluated at around 93% for sodium lauryl methyl ester sulfonate surfactant at 20 ppm and 87.2% at 50 ppm for sodium palmityl methyl ester sulfonate surfactant.

Keywords: carbon steel, oilfield, corrosion, anionic surfactants

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Authors: Hui Ling Chen

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This article describes the experience of caring for a 68-year-old lung cancer patient undergoing the initial stage of concurrent chemotherapy and radiation therapy during the period of October 21 to November 16. In this study, the author collected data through observation, interviews, medical examination, and the use of Roy’s adaptation model as a guide for data collection and assessment. This study confirmed that chemotherapy induced nausea and vomiting, and radiation therapy impaired skin integrity. At the same time, the patient experienced an anxious reaction to the initial cancer diagnosis and the insertion of subcutaneous infusion ports at the start of medical treatment. Similarly, the patient’s wife shares his anxiety, not to mention the feeling of inadequacy from the lack of training in cancer care. In response, the nursing intervention strategy has included keeping the patient and his family informed of his treatment progress, transfer of cancer care knowledge, and providing them with spiritual support. For example, the nursing staff has helped them draw up a mutually agreeable dietary plan that best suits the wife’s cooking skills, provided them with knowledge in pre- and post-radiation skin care, as well as means to cope with nausea and vomiting reactions. The nursing staff has also worked on building rapport with the patient and his spouse, providing them with encouragement, caring attention and companionship. After the patient was discharged from the hospital, the nursing staff followed up with caring phone calls to help the patient and his family make life-style adjustments to normalcy. The author hopes that his distinctive nursing experience can be useful as a reference for the clinical care of lung cancer patients undergoing the initial stage of concurrent chemotherapy and radiation therapy treatment.

Keywords: lung cancer, initiate diagnosis, concurrent chemotherapy and radiation therapy, nursing care

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Authors: Nalan Kaya, Gonca Ozan, Elif Erdem, Neriman Colakoglu, Enver Ozan

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The toxic effects of tobacco smoke exposure have been detected in numerous studies. Ellagic acid (EA), (2,3,7,8-tetrahydroxy [1]-benzopyranol [5,4,3-cde] benzopyran 5,10-dione), a natural phenolic lactone compound, is found in various plant species including pomegranate, grape, strawberries, blackberries and raspberries. Similar to the other effective antioxidants, EA can safely interact with the free radicals and reduces oxidative stress through the phenolic ring and hydroxyl components in its structure. The aim of the present study was to examine the protective effects of ellagic acid against oxidative damage on lung tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. Equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Lung tissues and blood samples were taken. The lung slides were stained by H&E and Masson’s Trichrome methods. Also, galactin-3 stain was applied. Biochemical analyzes were performed. Vascular congestion and inflammatory cell infiltration in pulmonary interstitium, thickness in interalveolar septum, cytoplasmic vacuolation in some macrophages and galactin-3 positive cells were observed in histological examination of tobacco smoke group. In addition to these findings, hemorrhage in pulmonary interstitium and bronchial lumen was detected in tobacco smoke + corn oil group. Reduced vascular congestion and hemorrhage in pulmoner interstitium and rarely thickness in interalveolar septum were shown in tobacco smoke + EA group. Compared to group-I, group-II GSH level was decreased and MDA level was increased significantly. Nevertheless group-IV GSH level was higher and MDA level was lower than group-II. The results indicate that ellagic acid could protect the lung tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, lung, rat, tobacco smoke

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Authors: A. Altomi, A. Alhebshi, M. Rasm, B. Osman

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This study explored the application of chitin nanocrystals (ChiNCs), derived from a renewable and environmentally friendly material, as stabilizers for oil-in-water (O/W) emulsions. O/W emulsions are commonly used in various applications but are prone to instability and degradation over time. Instability can occur due to factors such as flocculation, coalescence, and gravitational separation, including creaming and sedimentation, either independently or simultaneously. To produce ChiNCs, chitin powder underwent acid hydrolysis. Transmission electron microscopy (TEM) analysis revealed that ChiNCs exhibited a needle-like morphology, with lengths ranging from 200 to 800 nm and widths ranging from 20 to 80 nm. The surface charge of ChiNCs was negative at pH values above 7 and positive at pH values below 7. The rheological properties of O/W emulsions stabilized by ChiNCs were compared to those stabilized by synthetic surfactants, namely Tween 80 and CTAB. The emulsions stabilized by ChiNCs demonstrated higher yield stress and lower shear viscosity compared to those stabilized by synthetic surfactants. This indicates that ChiNC-stabilized emulsions are more stable and less prone to breakdown. Based on these findings, ChiNCs show promise as an alternative to synthetic surfactants for stabilizing O/W emulsions.

Keywords: chitin nanocrystals, colloidal pickering, emulsion rheology, oil-in-water, synthetic surfactant

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Selim M. Khan, Aaron A. Goodarzi, Joshua M. Taron, Tryggve Rönnqvist

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Indoor air quality, a prime determinant of health, is strongly influenced by the presence of hazardous radon gas within the built environment. As a health issue, dangerously high indoor radon arose within the 20th century to become the 2nd leading cause of lung cancer. While the 21st century building metrics and human behaviors have captured, contained, and concentrated radon to yet higher and more hazardous levels, the issue is rapidly worsening in Canada. It is established that Canadians in the Prairies are the 2nd highest radon-exposed population in the world, with 1 in 6 residences experiencing 0.2-6.5 millisieverts (mSv) radiation per week, whereas the Canadian Nuclear Safety Commission sets maximum 5-year occupational limits for atomic workplace exposure at only 20 mSv. This situation is also deteriorating over time within newer housing stocks containing higher levels of radon. Deep machine learning (LSTM) algorithms were applied to analyze multiple quantitative and qualitative features, determine the most important contributory factors, and predicted radon levels in the known past (1990-2020) and projected future (2021-2050). The findings showed gradual downwards patterns in Sweden, whereas it would continue to go from high to higher levels in Canada over time. The contributory factors found to be the basement porosity, roof insulation depthness, R-factor, and air dynamics of the indoor environment related to human window opening behaviour. Building codes must consider including these factors to ensure adequate indoor ventilation and healthy living that can prevent lung cancer in non-smokers.

Keywords: radon, building metrics, deep learning, LSTM prediction model, lung cancer, canada, sweden

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: Seyedeh Sepideh Amini, Navideh Aghaei Amirkhizi, Seyedeh Paniz Amini, Seyed Soheil Sayyahi, Mohammad Reza Davar Panah

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CT-Scan is one of the lateral and sectional imaging methods that produce 3D-images with use of rotational x-ray tube around central axis. This study is about evaluation and calculation of effective doses around heart organs such as breast, lung and liver with CT-Scan 128 dual sources with TLD_100 and RANDO Phantom by spiral, flash and conventional protocols. In results, it is showed that in spiral protocol organs have maximum effective dose and minimum in flash protocol. Thus flash protocol advised for children and risk persons.

Keywords: X-ray computed tomography, dosimetry, TLD-100, RANDO, phantom

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Authors: Rabih O. Al-Kaysi, Lingyan Zhu, Muhannah K. Al-Muhannah, Christopher J. Bardeen

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(E)-3-(Anthracen-9-yl)acrylic acid (9-AYAA) 1 exhibits a strong photomechanical response in bulk crystals but is challenging to grow in microcrystalline form. High quality microcrystals of this molecule could not be grown using techniques like sublimation, reprecipitation, and the floating drop method. If the tertbutyl ester of 9-AYAA is used as a starting material, however, high quality, size-uniform microwires could be grown via acid catalyzed hydrolysis. 9-AYAA microwires with uniform length and thickness were produced after a suspension of (E)-tert-butyl 3-(anthracen-9-yl)acrylate ester 2 microparticles was tumble-mixed in a mixture of phosphoric acid and sodium dodecyl sulfate at 35 °C. The dependence of the results on temperature, surfactant and precursor concentration, and mixing mode was investigated. This chemical reaction-growth method was extended to grow microplates of 9-anthraldehyde 3 using the corresponding acylal 4 as the starting material. Under 475 nm irradiation, the 9-AYAA microwires undergo a photoinduced coiling–uncoiling transition, while the 9-anthraldehyde microplates undergo a folding–unfolding transition.

Keywords: photomechanical, surfactant, organic crystals, uniform

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Laure Wiest, Barbara Giroud, Azziz Assoumani, Francois Lestremau, Emmanuelle Vulliet

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Due to their production at high tonnages and their extensive use, surfactants are contaminants among those determined at the highest concentrations in wastewater. However, analytical methods and data regarding their occurrence in river water are scarce and concern only a few families, mainly anionic surfactants. The objective of this study was to develop an analytical method to extract and analyze a wide variety of surfactants in a minimum of steps, with a sensitivity compatible with the detection of ultra-traces in surface waters. 27 substances, from 12 families of surfactants, anionic, cationic and non-ionic were selected for method optimization. Different retention mechanisms for the extraction by solid phase extraction (SPE) were tested and compared in order to improve their detection by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The best results were finally obtained with a C18 grafted silica LC column and a polymer cartridge with hydrophilic lipophilic balance (HLB), and the method developed allows the extraction of the three types of surfactants with satisfactory recoveries. The final analytical method comprised only one extraction and two LC injections. It was validated and applied for the quantification of surfactants in 36 river samples. The method's limits of quantification (LQ), intra- and inter-day precision and accuracy were evaluated, and good performances were obtained for the 27 substances. As these compounds have many areas of application, contaminations of instrument and method blanks were observed and considered for the determination of LQ. Nevertheless, with LQ between 15 and 485 ng/L, and accuracy of over 80%, this method was suitable for monitoring surfactants in surface waters. Application on French river samples revealed the presence of anionic, cationic and non-ionic surfactants with median concentrations ranging from 24 ng/L for octylphenol ethoxylates (OPEO) to 4.6 µg/L for linear alkylbenzenesulfonates (LAS). The analytical method developed in this work will therefore be useful for future monitoring of surfactants in waters. Moreover, this method, which shows good performances for anionic, non-ionic and cationic surfactants, may be easily adapted to other surfactants.

Keywords: anionic surfactant, cationic surfactant, LC-MS/MS, non-ionic surfactant, SPE, surface water

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Authors: Jos Olijve

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Introduction and Purpose: Endotoxins are found in the outer membrane of gram-negative bacteria and have profound in vitro and in vivo responses. They can trigger strong immune responses and negatively affect various cellar activities particular cells expressing toll-like receptors. They are therefore unwanted contaminants of biomaterials sourced from natural raw materials, and their activity must be as low as possible. Collagen and gelatin are natural extracellular matrix components and have, due to their low allergenic potential, suitable biological properties, and tunable physical characteristics, high potential in biomedical applications. The purpose of this study was to determine the influence of autoclave sterilization of gelatin on physical properties and endotoxin level compared to surfactant purified gelatin. Methods: Type A gelatin from Sigma-Aldrich (G1890) with endotoxin level of 35000 endotoxin units (EU) per gram gelatin and type A gelatins from Rousselot Gent with endotoxin activity of 30000 EU per gram were used. A 10 w/w% G1890 gelatin solution was autoclave sterilized during 30 minutes at 121°C and 1 bar over pressure. The physical properties and the endotoxin level of the sterilized G1890 gelatin were compared to a type A gelatin from Rousselot purified with Triton X100 surfactant. The Triton X100 was added to a concentration of 0.5 w/w% which is above the critical micellar concentration. The gelatin surfactant mixtures were kept for 30-45 minutes under constant stirring at 55-60°C. The Triton X100 was removed by active carbon filtration. The endotoxin levels of the gelatins were measured using the Endozyme recombinant factor C method from Hyglos GmbH (Germany). Results and Discussion: Autoclave sterilization significantly affect the physical properties of gelatin. Molecular weight of G1890 decreased from 140 to 50kDa, and gel strength decreased from 300 to 40g. The endotoxin level of the gelatin reduced after sterilization from 35000 EU/g to levels of 400-500 EU/g. These endotoxin levels are however still far above the upper endotoxin level of 0.05 EU/ml, which resembles 5 EU/g gelatin based on a 1% gelatin solution, to avoid cell proliferation alteration. Molecular weight and gel strength of Rousselot gelatin was not altered after Triton X100 purification and remained 150kDa and 300g respectively. The endotoxin levels of Triton X100 purified Rousselot gelatin was < 5EU/g gelatin. Conclusion: Autoclave sterilization of gelatin is, in comparison to Triton X100 purification, not efficient to inactivate endotoxin levels in gelatin to levels below the upper limit to avoid cell proliferation alteration. Autoclave sterilization gave a significant decrease in molecular weight and gel strength which makes autoclave sterilized gelatin, in comparison to Triton X100 purified gelatin, not suitable for 3D printing.

Keywords: endotoxin, gelatin, molecular weight, sterilization, Triton X100

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Authors: Jaiden X. Schraut

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Medical Imaging Segmentation of Chest X-rays is used for the purpose of identification and differentiation of lung cancer, pneumonia, COVID-19, and similar respiratory diseases. Widespread application of computer-supported perception methods into the diagnostic pipeline has been demonstrated to increase prognostic accuracy and aid doctors in efficiently treating patients. Modern models attempt the task of segmentation and classification separately and improve diagnostic efficiency; however, to further enhance this process, this paper proposes a multi-output network that follows a U-Net architecture for image segmentation output and features an additional CNN module for auxiliary classification output. The proposed model achieves a final Jaccard Index of .9634 for image segmentation and a final accuracy of .9600 for classification on the COVID-19 radiography database.

Keywords: chest X-ray, deep learning, image segmentation, image classification

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Authors: Anna Wolowicz, Katarzyna Staszak, Zbigniew Hubicki

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Nowadays heavy metal ions as well as surfactants are widely used throughout the world due to their useful properties. The consequence of such widespread use is their significant production. On the other hand, the increasing demand for surfactants and heavy metal ions results in production of large amounts of wastewaters which are discharged to the environment from mining, metal plating, pharmaceutical, cosmetic, fertilizer, paper, pesticide and electronic industries, pigments producing, petroleum refining and from autocatalyst, fibers, food, polymer industries etc. Heavy metal ions are non-biodegradable in the environment, cable of accumulation in living organisms and organs, toxic and carcinogenic. On the other hand, not only heavy metal ions but also surfactants affect the purity of water and soils. Some of surfactants are also toxic, harmful and dangerous because they are able to penetrate into surface waters causing foaming, blocked diffusion of oxygen from the atmosphere and act as emulsifiers of hydrophobic substances and increase solubility of many the dangerous pollutants. Among surfactants the anionic ones dominate and their share in the global production of surfactants is around 50 ÷ 60%. Due to the negative impact of heavy metals and surfactants on aquatic ecosystems and living organisms, removal and monitoring of their concentration in the environment is extremely important. Surfactants and heavy metal ions removal can be achieved by different biological and physicochemical methods. The adsorption as well as the ion-exchange methods play here a significant role. The aim of this study was heavy metal ions removal from aqueous solutions using different types of ion exchangers in the presence of anionic surfactants. Preliminary studies of copper(II), nickel(II), zinc(II) and cobalt(II) removal from acidic solutions using ion exchangers (Lewatit MonoPlus TP 220, Lewatit MonoPlus SR 7, Purolite A 400 TL, Purolite A 830, Purolite S 984, Dowex PSR 2, Dowex PSR3, Lewatit AF-5) allowed to select the most effective ones for the above mentioned sorbates and then to checking their removal efficiency in the presence of anionic surfactants. As it was found out Lewatit MonoPlus TP 220 of the chelating type, show the highest sorption capacities for copper(II) ions in comparison with the other ion exchangers under discussion, e.g. 9.98 mg/g (0.1 M HCl); 9.12 mg/g (6 M HCl). Moreover, cobalt(II) removal efficiency was the highest in 0.1 M HCl using also Lewatit MonoPlus TP 220 (6.9 mg/g) similar to zinc(II) (9.1 mg/g) and nickiel(II) (6.2 mg/g). As the anionic surfactant sodium dodecyl sulphate (SDS) was used and surfactant parameters such as viscosity (η), density (ρ) and critical micelle concentration (CMC) were obtained: η = 1.13 ± 0,01 mPa·s; ρ = 999.76 mg/cm3; CMC = 2.26 g/cm3. The studies of copper(II) removal from acidic solutions in the presence of SDS of different concentration show negligible effects on copper(II) removal efficiency. The sorption capacity of Cu(II) from 0.1 M acidic solution of 500 mg/L initial concentration was equal to 46.8 mg/g whereas in the presence of SDS 45.3 mg/g (0.1 mg SDS/L), 47.1 mg/g (0.5 mg SDS/L), 46.6 mg/g (1 mg SDS/L).

Keywords: anionic surfactant, heavy metal ions, ion exchanger, removal

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Authors: Hossein Barri Ghazani

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Transfusion-related acute lung injury is the main reason of transfusion-related death, and it’s assigned to white blood cell reactive antibodies present in the blood product (anti-HLA class I and class II or anti granulocyte antibodies). TRALI may occur in the COVID-19 patients who are treated by convalescent plasma. The rate of TRALI’s reactions is the same in both males and females and can happen in all age groups. TRALI’s occurrence is higher for people who receive plasma from female donors because the parous female donors have multiple HLA antibodies in their plasma. Patients with chronic liver disease have an augmented risk of transfusion-related acute lung injuries from plasma containing blood products like FFP and PRP. The condition of TRALI suddenly starts with a non‐cardiogenic pulmonary Edema, often accompanied by marked systemic hypovolemic and hypotension. The conditions occur during or within a few hours of transfusion. Chest X-ray shows a nodular penetration or bats’ wing pattern of Edema which can be seen in acute respiratory distress syndrome as well. TRALI can occur with any type of blood products and can occur with as little as one unit. The blood donor center should be informed of the suspected TRALI reactions when the symptoms of TRALI are observed. After a review of the clinical data, the donors must be screened for granulocyte and HLA antibodies. The diagnosis and management of TRALI is not simple and is best done with a professional team and a specialty skilled nurse experienced with the upkeep of these patients.

Keywords: TRALI, transfusion-related death, anti-granulocyte antibodies, anti-HLA antibodies, COVID-19

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Authors: Helen Zhang

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Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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Authors: Riam Abu-Much, Muhamad Hugerat

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Nanoscience has become one of the main science fields in the world; its importance is reflected in both society and industry; therefore, it is very important to intensify educational programs among teachers and students that aim to introduce "Nano Concepts" to them. Two different lab activities were developed for demonstrating the importance of nanoscale materials using unique points of view. In the first, electrical conductive films made of silver nanoparticles were fabricated. The silver nanoparticles were protected against aggregation using electrical conductive polypyrrole, which acts also as conductive bridge between them. The experiments show a simpler way for fabricating conductive thin film than the much more complicated and costly conventional method. In the second part, the participants could produce emulsions of liposome structures using Phosphatidylcholine as a surfactant, and following by minimizing the size of it from micro-scale to nanometer scale (400 nm), using simple apparatus called Mini-Extruder, in that way the participants could realize the change in solution transparency, and the effect of Tyndall when the size of the liposomes is reduced. Freshmen students from the Academic Arab College for Education in Haifa, Israel, who are studying to become science teachers, participated in this lab activity as part of the course "Chemistry in the Lab". These experiments are appropriate for teachers, high school and college students.

Keywords: case study, colloid, emulsion, liposome, surfactant

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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