Search

The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics ( n = 555), MetS ( n = 334), and ASMetS cases ( n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

Cytokine storm is the most prominent hallmark in patients with coronavirus disease 2019 (COVID-19) that stimulates the free radical storm, both of which induce an overactive immune response during viral infection. We hypothesized that owning to its radical-scavenging and anti-inflammatory properties, Edaravone could reduce multi-organ injury, clinical complications, and mortality in severe COVID-19 cases. This single-center randomized clinical trial was accompanied in the intensive care units (ICUs) of the teaching hospital of Tabriz University of Medical Sciences to evaluate the effect of Edaravone on the outcome of patients with severe COVID-19. Thirty-eight patients admitted to ICU were included and randomized into two control and intervention arms. Patients in the intervention group received 30 mg Edaravone by slow intravenous infusion for three days in addition to receiving national therapy. The primary outcome was the need for intubation, the intubation length, and mortality rate. Secondary endpoints were clinical improvement. Edaravone administration improved the primary outcomes; it decreased the need for endotracheal intubation and mechanical ventilation [10.52% (n = 2) versus 42.1% (n = 8); p = 0.03] and intubation length [3 (1-7) versus 28 (4-28), p = 0.04] compared to control group. Baseline characteristics and laboratory tests were similar between the studied groups. No marked differences were observed in secondary endpoints (p 0.05). Administration of Edaravone could decrease the need for mechanical ventilation and length of intubation in severe COVID-19 patients admitted to ICU.

Introduction Airway hyper-responsiveness (AHR) is a characteristic feature of asthma. The aim of this study was to compare the impulse oscillometry (IOS) and spirometry to methacholine for AHR detection among individuals with clinically hyper-reactive airway disease suggestive of bronchial asthma and baseline spirometry were normal. Materials and methods Adults with symptoms suggestive of AHR and normal baseline spirometry test were selected. The short protocol of methacholine challenge test (MCT) was performed for all subjects using IOS and spirometry simultaneously. The primary endpoint was to compare the methacholine dosage causing a 20% drop in forced expiratory volume in one second (FEV1), with methacholine dosage that causing 40% increasing the baseline respiratory resistance at 5 hertz (R5), as measured by IOS. Result A total of 235 participants were analyzed, 184 (78.2%) had positive test results with R5, while 81 (34.4%) had positive MCT results with FEV1.The sensitivity and specificity of MCT with R5were 87.3%, 64.6%, and MCT with FEV1 were 39.1%, 85.4%, respectively. The area under the receiver operating characteristic (ROC) curve was greater at lower doses of MCT at R5, (AUROC: 0.653; p= 0.01). Conclusions The results showed higher sensitivity, negative predictive value, and earlier response of the short protocol of MCT with IOS, compared to MCT with spirometry. Our study suggested the utility of IOS in addition to conventional spirometry as a method of choice in MCT for detection of AHR.

Background Chronic obstructive pulmonary disease (COPD) is a common lung disease during middle age which one of its complications is depression. Depression is considered one of the major causes of severe disability worldwide. One of the factors that affect the severity and incidence of this disease is a lifestyle, especially dietary pattern. On the other hand, some studies showed the relationship between dietary patterns and depression. The present study aims to investigate the dietary patterns of people with chronic obstructive pulmonary disease and its association with depression. Methods The present cross-sectional study was performed on 220 patients (mean ± SD age = 54.58 ± 5.08) with chronic obstructive pulmonary disease (56.6% men, 43.4% women) from Tabriz, Iran. Questionnaires of general information, food frequency, Beck depression and physical activity were completed. The dominant dietary patterns were determined by factor analysis, and their relationship with depression was discussed by regression analysis. Results Three dominant dietary patterns were identified as healthy, unhealthy, and mixed dietary patterns. An inverse relationship was found between healthy and mixed dietary patterns with depression. There is no meaningful connection between unhealthy dietary patterns and depression. Depression had a significant inverse relationship with physical activity. There was no relationship between dietary patterns and Forced Expiratory Volume for 1 s (FEV1) and Forced Vital Capacity (FVC) criteria. A positive and significant relationship was observed between mixed dietary patterns with FEV1/FVC. Conclusion Inverse relationships exist between healthy dietary patterns and depression in patients with COPD, and improves the function of the lungs. Further studies are needed to show the exact relationship between diet and COPD depression.

Aim In recent years, mobile applications have been developed for health education purposes. The aim of this study was to determine whether Telegram‐based virtual education versus in‐person education can be effective for improving the quality of life in adolescents with moderate‐to‐severe asthma. Design A single‐blind randomized trial. Methods Participants were 64 adolescents aged 12–19 years and were equally assigned randomly to group A (Telegram‐based education) and group B (in‐person education) during 22 June 2017–19 February 2018. The educational contents were similar for both groups. The Mini Pediatric Asthma Quality of Life Questionnaire was used prior to intervention and 5 weeks postintervention for both groups of adolescents. Results A statistically significant increase was observed in the quality of life in both groups (p

The work productivity and activity impairment (WPAI) questionnaire is a fine linguistic validated tool to measure work productivity and activity impairment. Considering its capability, this study aimed to evaluate the validity of the Persian version of WPAI-AQ in asthmatics.The standard forward-backward process was used to translate the English version of WPAI-AQ into Persian. The convergent validity and responsiveness were evaluated by analyzing the correlations between the Persian WPAI-AQ and the health outcomes, and its longitudinal change score with the change in SGRQ score, respectively. Additionally, the stability was estimated according to test-retest scores.There was a significant correlation between the Persian WPAI-AQ related outcomes and symptoms, activities, and impacts of disease (r = 0.41-0.89, p 0.04). Desirable stability was observed by the test-retest analysis; 0.90 (95%CI: 0.89-0.95) for overall impairment, 0.90 (95%CI: 0.86-0.93) for work time missed, 0.72 (95%CI: 0.54-0.83) for activity impairment; 0.79 (95%CI: 0.71-0.86) for student class time missed, and 0.76 (95%CI: 0.66-0.81) for school impairment. Response to the change scores strongly supported the longitudinal responsiveness of the Persian WPAI-AQ (r = 0.37 to 0.63, p 0.05).The Persian WPAI-AQ is a feasible valid tool to estimate work productivity and activity impairment in Persian-speaking asthmatic patients.

Background Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID‐19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID‐19. Methods In this randomised clinical trial, hospitalised patients with COVID‐19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30‐day mortality rate and length of hospital stay. Results The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30‐day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). Conclusions There was no priority in losartan or amlodipine administration in COVID‐19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first‐line anti‐HTN medications in COVID‐19.

Background Systemic sclerosis (SSc) is a connective tissue disease and one of the manifestations associated with this disease is pulmonary involvement. Studies showed that endothelin 1 (ET-1) plays a role in pulmonary dysfunction due to SSc. The aim of this study was to determine the level of ET-1 in SSc patients and to evaluate its association with the early stages of pulmonary fibrosis. Methods In this cross-sectional study, 48 patients with SSc were enrolled in the study. The stiffness of the skin was evaluated based on the modified Rodnan skin score. CT records, lung function tests and echocardiography were done. The samples were divided into two groups of patients with and without pulmonary parenchymal involvement. Blood sample was taken to measure the serum levels of ET-1 by ELISA method. ANOVA and Tukey HSD tests were used for statistical analysis. Results According to pulmonary CT scan, 68.2% of patients had pulmonary involvement. There was no significant difference in the presence of honeycomb lesions and fibrosis in lung CT scan of the patients in case of gender (P = 0.819 and P = 0.356, respectively). There was no statistical difference between the results of spirometry in patients with anti-Scl-70 and anti-centromere test. The mean serum level of ET-1 in the studied population was 0.55 ± 0.232 pg/mL, in the men was 0.47 ± 0.14 pg/mL and in the women was 0.55 ± 0.24 pg/mL. There was no significant difference between the two groups in the case of gender and type of the disease (P = 0.475 and P = 0.150, respectively). The ROC diagram of serum level of ET1 in patients based on the type of the disease shows that the serum level of ET-1 of 55% has 50% sensitivity and 52.2% specificity. Conclusion Serum level of ET-1 could not be used for screening of pulmonary involvement in SSc because its sensitivity and specificity is related to pulmonary fibrosis, honeycomb lesions and disease form. Anti Scl-70 with low levels, DLCO, FVC, FEV1, TLC can be used to assess the possibility of pulmonary involvement and response to treatment.

Background Chronic obstructive pulmonary disease (COPD) has been introduced as a major public health problem. It has been suggested that disruption in function or some adipokines and serum proteins' signaling could play crucial roles in lung diseases. This study's purpose was to investigate the association between serum levels of S100A1, ZAG, and adiponectin with FEV1 in COPD patients. Methods In this cross-sectional study, 90 clinically stable outpatient males with age ranging from 40 to 70 years with COPD diagnosis - FEV1/FVC Results In the present study, lower FEV1 was significantly associated with increased risk of cachexia (OR = 5.76, 95% CI: 2.28-14.54). The serum level of ZAG was significantly higher in the mild-moderate COPD patients in comparison with the severe-very severe COPD patients (p 0.800, p Conclusion In the present study, we found that low FEV1 was associated with increased risk of cachexia in COPD patients. Additionally, lower serum level of ZAG and higher RMR were observed in patients with severe-very severe COPD as compared to mild-moderate COPD. Therefore, it could be claimed that there is a mechanistic chain of causality between FEV1, serum ZAG, RMR, and cachexia.

Introduction: Pleural effusion (PE) is a common manifestation of pulmonary and non–pulmonary diseases, and the first step for diagnosing the etiology is analysis of pleural fluid. The aim of this study was to determine the epidemiology of PE in a tertiary referral hospital in the North-West of Iran. Methods: All patients with PE who referred to the department of pulmonary diseases in tertiary centre of Tabriz University of Medical Sciences between 2015 and 2016 were enrolled. Complete enumeration method used for selection of patients. Required information including clinical findings, PE location, fluid appearance, and biochemical characteristics were recorded using a checklist and analyzed via appropriate statistical methods. Results: A total of 223 patients were included in this study. Congestive heart failure (CHF) was the most common cause of PE (n=67), followed by pulmonary thromboembolism and malignant diseases. PE fluid in all patients with CHF was transudative. Conclusion: According to the findings of this study, CHF was the most prevalent cause of PE.

BACKGROUND: Epithelial malignancy in lung cancer, which is initiated with myofibroblast differentiation and remodeling, promotes hypoxia and intracellular ROS generation most affected by the prototypical enzyme, NADPH oxidase 4 (NOX4). In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a critical transcription factor by stimulating antioxidant proteins as redox homeostasis regulators. The aim of this study was to investigate a possible correlation between lung tissue NOX4 and Nrf2 genes (NOX4 and Nrf2) mRNA expression and bronchoalveolar lavage fluid (BALF) protein expression in non-small-cell lung carcinoma (NSCLC) patients. METHODS: Samples from 25 patients with various NSCLC types and stages and 20 healthy controls were collected. NOX4 and Nrf2 mRNA were measured by qRT-PCR, and protein by western blot analysis. RESULTS: NOX4 mRNA and protein expression was significantly up-regulated in NSCLC patients’ lung tissues and BALFs (p= 0.03 and 0.01, respectively). In addition, by adjusting for age, sex, and NSCLC types and stages, a significant and positive correlation was observed between NOX4 and Nrf2 mRNA expression (r= 0.927, p= 0.001). This was also true when not adjusted as above (r= 0.944, p< 0.001). CONCLUSION: NOX4 mRNA and protein expression is significantly up-regulated in NSCLC patients’ lung tissues and BALFs, and NOX4 and Nrf2 mRNA expression is positively correlated in NSCLC tissues.

Background: The red cell distribution width (RDW) value has been recently recognized as a valuable biomarker in clinical practice. The RDW value has not been evaluated so far in patients with pleural effusion. Thus, this study aimed to investigate whether RDW could distinguish between exudative and transudative pleural effusions. Materials and Methods: We measured protein and lactate dehydrogenase levels on both pleural fluids and serum samples from 223 cases and classified them as transudates or exudates based on the classic Light’s criteria. We collected blood cell count elements such as RDW from the medical records. We also investigated the correlation between RDW and the nature of pleural effusion. Results: In 55.2% of the patients, pleural fluid was exudative. Although we found no significant association between RDW and the nature of the pleural fluid, we detected a significantly higher amount of RDW (14.9 ≤) in patients with exudative pleural effusion compared to transudate (66.7% vs. 33.3%; P= 0.01). In this category, neoplastic conditions were mostly observed in the patients (76.3%), followed by pulmonary thromboembolism (21.1%) and systemic lupus erythematous (2.6%). Conclusion: The findings could not reveal any noticeable correlation between RDW and the Light criteria. However, it appears that elevated RDW levels give insights into the valuable nature of RDW in different conditions such as neoplastic diseases.

Background. Risk scores are urgently needed to assist clinicians in predicting the risk of death in severe patients with SARS-CoV-2 infection in the context of millions of people infected, rapid disease progression, and shortage of medical resources.Method. A total of 139 severe patients with SARS-CoV-2 from China and Iran were included. Using data from China (training dataset, n = 96), prediction models were developed based on logistic regression models, nomogram and risk scoring system for simplification. Leave-one-out cross validation was used for internal validation and data from Iran (test dataset, n = 43) for external validation. Results. The NSL model (Area under the curve (AUC) 0.932) and NL model (AUC 0.903) were developed based on neutrophil percentage (NE), lactate dehydrogenase (LDH) with or without oxygen saturation (SaO2) using the training dataset. Compared with the training dataset, the predictability of NSL model (AUC 0.910) and NL model (AUC 0.871) were similar in the test dataset. The risk scoring systems corresponding to these two models were established for clinical application. The AUCs of the NSL and NL scores were 0.928 and 0.901 in the training dataset, respectively. At the optimal cut-off value of NSL score, the sensitivity was 94% and specificity was 82%. In addition, for NL score, the sensitivity and specificity were 94% and 75%, respectively.Conclusion. NSL and NL score are straightforward means for clinicians to predict the risk of death in severe patients. NL score could be used in selected regions where patients’ SaO2 cannot be tested.

Background: The relationship between dietary pattern and the risk of chronic obstructive pulmonary disease (COPD) has been described; however, the exclusive role of dietary factors remains controversial. Hence, we conducted this systematic meta-analysis to clarify the role of some nutrients and antioxidant vitamins in the risk of COPD. Materials and Methods: PubMed, Embase, and Scopus databases were searched for studies evaluating the associations between COPD outcome measures, symptoms, and mortality, and intake of fruits and vegetables, fiber, fish, n-3 or n-6 fatty acids, and antioxidant vitamins in adults. The random-effect model meta-analyses were used to pool the results. Results: Ten cohort, six case-control, and 20 cross-sectional studies were identified. The pooled relative risks (RRs) of the COPD and confidence intervals (CIs) for the highest intake group compared with the lowest intake group were 0.74 (95% CI: 0.65–0.85) for fruit, 0.65 (95% CI: 0.55–0.78) for dietary fiber, 0.71 (95% CI: 0.58–0.85) for fish, and 0.89 (95% CI: 0.76–0.99) for vitamin C. No association was observed between the risk of COPD and the intake of vegetables, n-3 fatty acids, vitamin E, and β-carotene; however, it was associated with n-6 fatty acids 1.06 (95% CI: 0.87–1.30). Conclusion: The results suggested that a higher intake of fruits, probably dietary fiber, and fish reduce the risk of COPD.

Introduction: Development of Ventilator-associated pneumoniae (VAP) presents an intricate chemistry comprising of intubation and invading bacteria which often are tied up with biofilm production. Aim: To assess the phenotypic and genetic basis of biofilm formation by gram negative bacilli isolated from mechanically ventilated and VAP developed patients. Materials and Methods: Endotracheal aspirate obtained from 40 mechanically ventilated patients was inoculated by a semi quantitative method. Isolation and identification of gram negative bacilli was done according to standard bacterial protocol followed by antibiotic susceptibility test and biofilm assessment by micro titer method. Presence of biofilm genes was studied by molecular method. Result: Amongst 40 enrolled hospitalized patients, 12.5% of them developed VAP. A. baumannii (n=68) was the commonest organism followed by P. aeruginosa (n=18), K. pneumoniae (n=32) and E. coli (n=12). Presence of multi drug (MDR) and extensive drug resistance (XDR) was evident in A. baumannii and P. aeruginosa comparative to K. pneumoniae and E. coli isolates. Moderate or strong biofilm production was an overt feature. Presence of bap gene was marked in 57.4% A. baumannii whereas, 11.1% P. aeruginosa displayed algC gene. Manifestation of genes fimH, ang43 and csgA was evident in 33.3%, 66.7% and 25% E. coli isolates respectively. Gene type 3 was present in all K. pneumoniae isolates while, mrkA and fimK genes were shown in 65.6% and 81.2% isolates respectively by multiplex PCR. Conclusion: Drug resistance phenotypes require specific national and regional therapeutic studies focusing on antimicrobial stewardship programs. Presence of biofilm requires routine surveillance of VAP, to track endemic VAPs.

BackgroundNowadays, a shift in age distribution and the increasing incidence of pertussis among adolescents and adults have been reported in the world. The aim of this study was to evaluate the prevalence, clinical characteristics, and seasonality of pertussis in Azerbaijan, Iran.MethodsA total of 3

Objective Lung cancer is one of the most common leading causes of cancer related death in the worldwide, thus its early detection might be a critical strategy to improve patients’ prognosis and survival. The present study was designed to assess if microRNAs expression profiling of bronchoalveolar lavage cell fraction and sputum could help to non-small cell lung cancer early detection. Materials and methods Relative expression of 3 selected microRNAs (miR-10b, miR-1 and miR-30a) were quantified using Real-time polymerase chain reaction in bronchoalveolar lavage cell fraction and sputum samples from non-small cell lung cancer cases (n = 30) and cancer-free group (n = 30). Written informed consent from all enrolled individuals was obtained. So, the Ethical and Scientific Committees of the participating institution confirmed the present study in accordance with the ethical standards (as laid down in 1964 Declaration of Helsinki). Results miR-1 and miR-30a were significantly downregulated in non-small-cell lung cancer patients , bronchoalveolar lavage and sputum while miR-10b was significantly upregulated. Overexpression of miR-10b has a positive strong correlation with clinical stages of cancer. ROC curve analysis of miR-10b (as oncomir) and miR-1 (as tumor suppressor) in bronchoalveolar lavage and sputum samples showed that miR-10b with 0.931 and 0.927 AUC values and miR-1 with 0.786 and 0.788 AUC values, could be an excellent and a fair candidate microRNA to distinguish non-small-cell lung cancer patients from cancer-free subjects, respectively. Conclusion This study reported significant differences in microRNAs expression in bronchoalveolar lavage and sputum samples of lung cancer patients compared to cancer-free subjects which represent a potential role as a highly specific and sensitive test to Improved early detection of non-small cell lung cancer.

Background Chronic obstructive pulmonary disease (COPD) has been introduced as a major public health problem. It has been suggested that disruption in function or some adipokines and serum proteins' signaling could play crucial roles in lung diseases. This study's purpose was to investigate the association between serum levels of S100A1, ZAG, and adiponectin with FEV1 in COPD patients. Methods In this cross-sectional study, 90 clinically stable outpatient males with age ranging from 40 to 70 years with COPD diagnosis – FEV1/FVC < 70% – were divided into two groups: mild–moderate COPD patients; FEV1 ≥ 50 (n=52) VS severe and very severe COPD patients; FEV1 < 50 (n=38). The serum levels of ZAG, S100A1, and adiponectin were measured by the use of enzyme-linked immunosorbent assay. Results In the present study, lower FEV1 was significantly associated with increased risk of cachexia (OR = 5.76, 95% CI: 2.28–14.54). The serum level of ZAG was significantly higher in the mild–moderate COPD patients in comparison with the severe–very severe COPD patients (p0.800, p

Circulating microRNAs have been recognized as promising biomarkers for the detection of lung cancer. The objective of this study was to evaluate miR-10b, miR-1 and, miR-30a in the plasma samples of lung cancer patients to confirm any possible relevance in the early detection of lung cancer. Plasma samples from 47 non-small-cell lung cancer patients and 41 cancer-free subjects were evaluated for selected microRNAs using the real-time PCR method. To evaluate the tobacco smoking effects on microRNAs expression, the studied groups were categorized into two subgroups: never-smokers and smokers. MiR-1/miR-30a expression levels were significantly reduced in lung cancer, while the miR-10b level was significantly elevated. We found that smoking had significant effects on the levels of circulating microRNAs in the smokers of the cancer-free group (a significant up-regulation of miR-10b and significant down-regulation of miR-1/miR-30a), and lung cancer patients (a significant elevation of miR-10b). Receiver operating characteristic curve analysis showed that miR-10b with an area under the curve of 0.861, and miR-1/miR-30a with values of0.905 and 0.889 for the same parameter, could distinguish non-small-cell lung cancer patients from cancer-free subjects. Our findings demonstrated significant differences in the expression of microRNAs in lung cancer and the considerable effects of smoking on microRNAs levels. Area under curve analysis showed that miR-10b with 78% sensitivity/78% specificity, miR-1 with 95% sensitivity/80% specificity and miR-30a with 87% sensitivity/83% specificity,might be good (miR-10b/miR-30a) and excellent (miR-1) markers for lung cancer detection.

Background Lung cancer is one of the most common types of fatal malignancies. Despite the remarkable advances in diagnosis and treatment approaches, most of the cases detected in late stages. Discovering novel markers to recognizing cancer in early stages require a deep understanding of molecular mechanisms. OSBPL3, the molecule belongs to the oxysterol-binding proteins (OSBP) family, involved in lipid metabolism and sterol transport; however, recent evidence considers the role of members of this family in cancer pathogenesis. We aimed to investigate the expression level of OSBPL3 in the tumor tissues of NSCLC patients. Methods By bronchoscopy procedure, 45 lung tissue samples including 25 cancerous and 20 non-cancerous control lung tissues were collected. The total RNA of them was extracted and then cDNA synthesized. Assessment of the OSBPL3 expression level was performed utilizing qRT-PCR. Results The significant increased mRNA expression level of OSBPL3 was observed in NSCLC tissues compared to the control of non-cancerous tissues (fold change = +2.38, P Conclusion Our data revealed the oncogenic function of OSBPL3 in NSCLC tissues. In case of confirmation of future studies, the mRNA expression level of OSBPL3 can be used as a biomarker for NSCLC diagnosis.

Background Lung cancer is one of the most common cancers worldwide whose prevalence and mortality have not any remarkable reduction in recent decades, in spite of the progression in screening and diagnostic methods. MiR-103, miR-184, miR-378, miR-497 and miR-506 are microRNAs which recent evidence has implied the possible roles of them in the carcinogenesis process. Hence, in this study we examined whether there are any significant alterations in the expression level of these micro RNAs during carcinogenesis procedure or not, and if we can use these factors as a diagnostic or prognostic biomarker for non-small cell lung cancer (NSCLC). Methods Fifty NSCLC patients participated in our study and tumor and adjacent normal tumor-free tissues were collected during the bronchoscopy. Total RNA was extracted from cells, cDNA was synthesized and then the expression level of target miRNAs was examined by quantitative Real-time PCR. Subsequently, expression levels of these genes and their correlation with clinicopathologic features of patients were analyzed with proper statistical tests. In these tests Pvalue Results The output data of our study showed the statistically significant down-expression of miR-103 (Fold change = 0.83, Pvalue = 0.036), miR-184a (Fold change = 0.52, Pvalue = 0.011), miR-378 (Fold change = 0.84, Pvalue = 0.041), and miR-497 (Fold change = 0.72, Pvalue = 0.021) between these micro-RNAs only mir-497 and miR-184a are potential biomarkers for NSCLC. Also, the expression levels of these miRNAs had significant relations with metastasis, lymph node involvement, and tumor cell differentiation degree and tumor size of NSCLC patients. Deregulated fifth microRNA, miR-506 was not statistically significant (Pvalue > 0.05). Conclusion According to the results of this study, 4 of our studied microRNAs have the potential to be used as diagnostic or prognostic biomarkers in case of confirmation of the future studies.

Highlights • SARS-CoV-2 mainly enter to CNS via direct (neuronal and hematologic route) and indirect route. • SARS-CoV-2 can infect leukocytes within the bloodstream and then cross the blood-brain-barrier via diapedesis. • SARS-CoV-2 can invade the vascular endothelium by binding to ACE-2, leading to increased permeability of blood-brain-barrier and then infecting glial cells in the CNS. • Future research is desirable to confirm or disprove such hypothesis., SARS-CoV-2 mainly invades respiratory epithelial cells by adhesion to angiotensin-converting enzyme 2 (ACE-2) and thus, infected patients may develop mild to severe inflammatory responses and acute lung injury. Afferent impulses that result from the stimulation of pulmonary mechano-chemoreceptors, peripheral and central chemoreceptors by inflammatory cytokines are conducted to the brainstem. Integration and processing of these input signals occur within the central nervous system, especially in the limbic system and sensorimotor cortex, and importantly feedback regulation exists between O2, CO2, and blood pH. Despite the intensity of hypoxemia in COVID-19, the intensity of dyspnea sensation is inappropriate to the degree of hypoxemia in some patients (silent hypoxemia). We hypothesize that SARS-CoV-2 may cause neuronal damage in the corticolimbic network and subsequently alter the perception of dyspnea and the control of respiration. SARS-CoV-2 neuronal infection may change the secretion of numerous endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. SARS-CoV-2 mainly enter to CNS via direct (neuronal and hematologic route) and indirect route. We theorize that SARS-CoV-2 infection-induced neuronal cell damage and may change the balance of endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. Thus, SARS-CoV-2-associated neuronal damage may influence the control of respiration by interacting in neuromodulation. This would open up possible lines of study for the progress in the central mechanism of COVID-19-induced hypoxia. Future research is desirable to confirm or disprove such a hypothesis.