The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies.

Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran Q statistic (with I2 statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-ß in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [P < 0.001 (Q statistics), I2 = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-ß and histopathological changes.

Oxidative/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease associated with disruption of alveolar epithelial cell layer and expansion of fibroblasts/myofibroblasts. Excessive levels of oxidative/nitrosative stress, induction of apoptosis, and insufficient autophagy may be involved in IPF pathogenesis; hence, the targeting of these pathways may ameliorate IPF. Areas covered: We describe the ameliorative effect of melatonin on IPF. We summarize the research on IPF pathogenesis with a focus on oxidative/nitrosative stress, autophagy and apoptosis pathways and discuss the potential effects of melatonin on these pathways. Expert opinion: Oxidative/nitrosative stress, apoptosis and autophagy could be interesting targets for therapeutic intervention in IPF. Melatonin, as a potent antioxidant, induces the expression of antioxidant enzymes, scavenges free radicals and modulates apoptosis and autophagy pathways. The effect of melatonin in the induction of autophagy could be an important mechanism against fibrotic process in IPF lungs. Further clinical studies are necessary to determine if melatonin could be a candidate for treating IPF.

Association of esophageal dilatation in chest CT scan with gastroesophageal reflux disease: A case control study.

The presence of increased air bubble in the lumina of esophagus on a chest CT scan may be associated with esophageal disorders. The purpose of this study was to determine the association between the appearance of air bubbles on chest CT scan and gastroesophageal Reflux Disease (GERD). In this case-control study, thirty-two patients with endoscopically proved GERD and 32 subjects without GERD underwent chest computed tomography (CT) scanning. Esophageal dilatation (ED) was defined as the presence of air bubbles greater than 10 mm in the supra ventricle (SV) and ventricle (CV), and air bubbles >15 mm in the ventricle to the lower esophageal sphincter (V-LES). The results were compared between the two groups. The GERD patients included 16 (50%) males with a mean age of 58.5±11.2 years and the control group included 17 (54.8%) males and 14 (45.1%) females with a mean age of 66.7±10.5 years. There was a significant relationship between the presence of GERD and esophageal dilation (ED) in the V-LES sections on the CT scan (P=0.002). The mean size of the air bubbles in the V-LES section was 11.73 mm in the case group in comparison to 4.32 mm in the control group (P<0.001).  The size and location of the air bubbles in the esophagus can vary and be important. The possibility of GERD increases in the presence of esophageal dilation on CT scan.

Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin.

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of lung function due to tissue scarring. A variety of pro-inflammatory and pro-fibrogenic factors including interleukin­17A, transforming growth factor ß, Wnt/ß­catenin, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factors, endotelin­1, renin angiotensin system and impaired caveolin­1 function are involved in the IPF pathogenesis. Current therapies for IPF have some limitations and this highlights the need for effective therapeutic agents to treat this fatal disease. Melatonin and its metabolites are broad-spectrum antioxidants that not only remove reactive oxygen and nitrogen species by radical scavenging but also up-regulate the expression and activity of endogenous antioxidants. Via these actions, melatonin and its metabolites modulate a variety of molecular pathways in different pathophysiological conditions. Herein, we review the signaling pathways involved in the pathophysiology of IPF and the potentially protective effects of melatonin on these pathways.

Long-term treatment with royal jelly improves bleomycin-induced pulmonary fibrosis in rats.

This study investigated the anti-fibrotic potential of royal jelly (RJ) powder against bleomycin-induced pulmonary fibrosis in rats. The rats were given RJ orally (25, 50, and 100 mg/kg per day) for 7 consecutive days before the administration of single intratracheal instillation of bleomycin (BLM) at 7.5 IU/kg. RJ doses were continued for 21 days after BLM exposure. Fibrotic changes in the lungs were studied by cell count and analysis of cytokine levels in the bronchoalveolar lavage fluid (BALF), histopathological examination, and assaying oxidative stress biomarkers in lung tissue. The results showed that BLM administration significantly increased the fibrotic changes, collagen content, and levels of malondialdehyde and decreased total thiol and glutathione peroxidase antioxidant contents in the rats' lung tissue. An increase in the level of cell counts and pro-inflammatory and pro-fibrotic cytokines such as TNF-α and TGF-ß in BALF was observed. Also, it significantly decreased IFN-γ, an anti-fibrotic cytokine, in BALF. However, RJ (50 and 100 mg/kg) reversed all of these biochemical indices as well as histopathological alterations induced by BLM. The present study demonstrates that RJ, by its antioxidant and anti-inflammatory properties, attenuates oxidative damage and fibrosis induced by BLM.

Effect of Eight-Week Aerobic, Resistive, and Interval Exercise Routines on Respiratory Parameters in Non-Athlete Women.

BACKGROUND: There are not many studies about the effects of physical activity on pulmonary function in normal population. However, it seems that strengthening and persevering respiratory muscles is an effective technique for improving pulmonary function. OBJECTIVE: The purpose of this study was to evaluate and compare the effects of eight-week aerobic, resistance, and interval exercise routines on respiratory parameters in non-athlete women. MATERIALS AND METHODS: Thirty-six non-athlete women between 18-25 years old participated in this prospective quasi-experimental trial. The subjects were randomly divided into three groups (aerobic, resistance and interval exercise, 12 in each group). Each group exercised three times a week for a total of eight weeks (24 sessions in total). Pulmonary function tests (PFT), including tidal volume (VT), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), inspiratory capacity (IC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first seconds (FEV1), the ratio of FEV1/FVC, peak inspiratory flow (PIF), and forced expiratory flow (FEF 25-75%) were recorded before and after the implementation of the exercise program for all participants. Data were analyzed using paired t-test and one-way ANOVA. RESULTS: The mean age of participants was 20.17 ± 2.13. The results of the paired T-test indicated that VC significantly increased in the group assigned to aerobic exercise (P = 0.028), while IC (P = 0.012) and PIF (P = 0.019) significantly increased in the group assigned to interval training. CONCLUSION: Our results showed that interval and aerobic exercise routines could improve pulmonary functions and aerobic and interval training can be used to increase VC, IC, PIF, in non-athlete women.