Clara Cell Protein Research Articles

Clinical significance of TLR7/IL-23/IL-17 signaling pathway in patients with acute respiratory distress syndrome

ObjectivesTo analyze the clinical significance of Toll-Like Receptor 7/Interleukin-23/Interleukin-17 (TLR7/IL-23/IL-17) signaling pathway in patients with Acute Respiratory Distress Syndrome (ARDS). MethodThe clinical data of 85 patients with ARDS were retrospectively analyzed and set as the ARDS group, and the clinical data of 85 healthy participants during the same period were set as the healthy control group. Univariate and multivariate logistic regression were used to analyze risk the factors affecting the prognosis of ARDS patients. ResultsTheTLR7 mRNA expression and IL-23 and IL-17 levels in peripheral blood mononuclear cells were higher in the ARDS group than in the control group (p < 0.05). TLR7 mRNA expression, IL-23, IL-17, Surfactant Protein-D (SP-D), and Clara Cell protein-16 (CC-16) levels were the highest in the severe group, followed by the moderate group, and the lowest in the mild group, while Oxygenation Index (OI) was the lowest in the severe group, followed by the moderate group, and the highest in the mild group (p < 0.05). Multivariate logistic regression analysis found that the disease grade (severe), TLR7 mRNA expression, IL-23 level, and IL-17 level were the risk factors affecting the 28-d survival status of ARDS patients (OR > 1, p < 0.05). ConclusionsIn ARDS patients, the TLR7/IL-23/IL-17 signaling pathway is activated. The expression of this pathway is closely related to the severity of the disease and the levels of lung injury markers, and it is a risk factor that may have a direct impact on the prognosis of ARDS patients.

Associations of Serum Clara Cell Protein 16 with Severity and Prognosis in Adults with Community-Acquired Pneumonia.

Clara cell protein 16 (CC16) has multiple functions, including antioxidant, anti-inflammatory, and immune regulation properties. Nevertheless, the concrete function of CC16 in adult patients with community-acquired pneumonia (CAP) remained blurred. A total of 541 adult patients with CAP were recruited on admission. Peripheral blood specimens, clinical parameters, and demographic characteristics were collected. The concentration of serum CC16 was evaluated through ELISA. The relationships between serum CC16 and clinical parameters were appraised by Spearman or Pearson correlative analyses. The correlations of serum CC16 with severity and prognosis were assessed using linear or logistic regression models. The level of CC16 was gradually decreased across with the elevated severity scores system of CAP. After treatment, the level of serum CC16 was upregulated. Correlative analyses found that serum CC16 was negatively related to inflammatory cytokines. Additionally, multivariate linear and logistic regression models revealed that serum CC16 was inversely associated with severity scores system. In addition, reduced serum CC16 on admission elevated the risks of vasoactive agent usage, ICU admission, and death during hospitalization. We observed an almost discriminatory ability for severity and death between serum CC16 and severity scores system, and were all obviously elevated compared to routine inflammatory and infectious markers. There are substantially inverse correlations between serum CC16 level on admission with severity scores and poorly prognostic outcomes, indicating that CC16 is involved in the pathophysiological process of CAP. This study is helpful for establishing the potential application of serum CC16 in risk evaluation and targeted treatment.

Investigation of serum surface active protein D and clara cell protein levels in workers exposed to silica dust in ferrous metal foundry

Objective: To investigate the levels of serum surface active protein D (SP-D) and clara cell protein (CCl6) in workers exposed to black silica dust, and analyze its influencing factors. Methods: From July to September 2021, 174 workers in 37 positions exposed to silica dust in 5 ferrous metal foundry were investigated by cross-sectional research method. The exposure concentration of silica dust workers was obtained through occupational health field investigation and detection, and the general situation of the study subjects was obtained through questionnaire survey and peripheral blood was collected. Double antigen sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of SP-D and CC16 in serum of workers. The mean values were compared by one-way ANOVA, and the influencing factors of SP-D and CC16 concentrations in serum were analyzed by ordered multiple logistic regression. Results: The time-weighted average concentration (C-TWA) of 174 workers exposed to silica dust (respirable dust) ranged from 0.09 mg/m(3)~3.58 mg/m(3), and the C-TWA overstandard rate of dust exposed workers was 32.18% (56/174) , with differences among workers in different positions (χ(2)=28.85, P<0.001) . The highest concentration of silica dust was (0.82±0.11) mg/m(3). Using C-TWA<50% OEL occupational exposure limit (OEL) as reference, serum SP-D concentration in workers with ≥50% OEL was increased (OR=4.95, 95%CI: 1.86~13.17, P=0.001) , while CC16 concentration was decreased (OR=0.15, 95%CI: 0.05~0.40, P<0.001) ; Serum CC16 concentration decreased in workers exposed to silica dust C-TWA≥OEL (OR=0.46, 95%CI: 0.28~0.98, P=0.043) . Compared with those with low occupational health literacy, the serum SP-D concentration of workers with high occupational health literacy decreased (OR=0.48, 95%CI: 0.25~0.92, P=0.027) and CC16 concentration increased (OR=2.09, 95%CI: 1.10-3.97, P=0.024) . Conclusion: When no abnormality was found in the physical examination of workers, the serum SP-D and CC16 concentration levels changed, and the change was related to the concentration of workers exposed to silica dust.

Long non-coding RNAs mediate the association between short-term PM2.5 exposure and circulating biomarkers of systemic inflammation

Although short-term fine particulate matter (PM2.5) exposure is associated with systemic inflammation, the effect of lncRNA on these association remains unknown. This study aims to investigate whether the plasma lncRNA mediate the effect of short-term PM2.5 exposure on systemic inflammation. In this cross-sectional study, plasma Clara cell protein 16 (CC16), interleukin 6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and lncRNA expression levels were measured in 161 adults between March and April in 2018 in Shijiazhuang, China. PM2.5 concentrations were estimated 0–3 days prior to the examination date and the moving averages were calculated. Multiple linear regressions were used to evaluate the associations between PM2.5, the four biomarkers and lncRNA expression levels. Mediation analyses were performed to explore the potential roles of lncRNA expression in these associations. The median concentration of PM2.5 ranged from 39.65 to 60.91 mg/m3 across different lag days. The most significant effects on IL-6 and TNF-α per interquartile range increase in PM2.5 were observed at lag 0–3 days, with increases of 0.70 pg/mL (95% CI: 0.33, 1.07) and 0.21 pg/mL (95% CI: 0.06, 0.36), respectively. While the associations between PM2.5 and IL-8 (0.68 pg/mL, 95% CI: 0.34, 1.02) and CC16 (3.86 ng/mL, 95% CI: 1.60, 6.13) were stronger at lag 0 day. Interestingly, a negative association between PM2.5 and the expression of four novel lncRNAs (lnc-ACAD11–1:1, lnc-PRICKLE1-4:1, lnc-GPR39–7:2, and lnc-MTRNR2L12–3:6) were observed at each lag days. Furthermore, these lncRNAs mediated the effects of PM2.5 on the four biomarkers, with proportions of mediation ranged from 2.27% (95% CI: 1.19%, 9.82%) for CC16 to 35.60% (95% CI: 17.16%, 175.45%) for IL-6. Our findings suggested that plasma lncRNA expression mediat the acute effects of PM2.5 exposure on systematic inflammation. These highlight a need to consider circulating lncRNA expression as biomarkers to reduce health risks associated with PM2.5.

Protective effect of dexmedetomidine on Tourniquet induced lung injury in patients undergoing total knee arthroplasty: A randomized trial

Objective To investigate whether dexmedetomidine (Dex) can reduce the severity of tourniquet-induced lung injury. Methods 36 patients undergoing total knee arthroplasty with a tourniquet were randomly assigned to the control (ischemia/reperfusion [I/R]) group and Dex group. Patients in the Dex group received a loading dose of Dex (0.8 μg/kg over 10 min intravenously) followed by continuous infusion of Dex (0.5 μg/kg/h intravenously) until the end of the surgery. The I/R group received an equal amount of 0.9% saline instead of Dex. The serum concentrations of tumor necrosis factor-α (TNF-α), Clara cell protein (CC-16), soluble receptor for advanced glycation end products (sRAGE), and brain-derived neurotrophic factor (BDNF) were measured and arterial blood gas analysis was performed before anesthesia and 30 min, 6 h, and 24 h after tourniquet release. Results In the I/R group, compared with baseline, the TNF-α, CC-16, and sRAGE concentrations were higher ( p &lt; 0.05) and the BDNF concentration was lower ( p &lt; 0.05) at most time points. In the Dex group, the TNF-α, CC-16, and sRAGE concentrations were lower than those in the I/R group ( p &lt; 0.05), whereas the concentration of BDNF was higher ( p &lt; 0.05). In the arterial blood gas analysis, the Dex group showed a significantly higher partial pressure of oxygen and arterial/alveolar oxygen tension ratio ( p &lt; 0.05) and a significantly lower alveolar/arterial oxygen tension difference than the I/R group ( p &lt; 0.05). Conclusion Dex administration partly inhibits the release of proinflammatory cytokines, affording protection against tourniquet-induced lung injury.

Inflammatory mediators in nasal secretions of patients with nasal polyposis with and without aspirin sensitivity.

The aim of this cross-sectional study was to compare the levels of inflammatory mediators in nasal secretions in patients with aspirin-exacerbated respiratory disease (AERD) and in those with nasal polyposis (NP) without aspirin-sensitivity and to correlate nasal fluid mediator concentrations with clinical parameters of the disease. A total of 30 patients with AERD, 30 chronic rhinosinusitis (CRS) with NP patients without aspirin sensitivity (CRSwNP), and 30 control subjects without inflammation of the nasal mucosa (C), selected for surgical treatment entered the study. The total nasal symptom score (TNSS), endoscopic score (ES), and Lund-Mackay score (LMS), were evaluated. The concentrations of eosinophil cationic protein (ECP), tryptase, heat shock protein 70 (HSP70), substance P and Clara cell protein 16 (CC16) were determined in nasal secretions. Higher concentrations of ECP, tryptase, and HSP70 were measured in the AERD patients than in the CRSwNP patients and the C group (p < .001; p < .001, respectively for all mediators). However, levels of CC16 were higher in the C group than in the AERD and CRSwNP groups (p < .001; p < .001, respectively). A positive correlation between the TNSS and CC16 and a negative one between CC16 and tryptase levels were found in the C group. The CRSwNP group showed positive correlations between ECP, HSP70, and tryptase and negative correlations between substance P, ES, and LMS, as well as between CC16 and tryptase levels. In the AERD group, we found a positive correlation between HSP70 and ECP levels and a negative correlation between the TNSS and CC16 concentration. The obtained results indicate the increased production of mediators of eosinophil and mast cell function, and the decreased production of biomarker of respiratory epithelial function in AERD patients. Clinical and biochemical parameters correlate in different ways in the AERD and CRSwNP patients.

The Potential CC16 (Clara Cell Protein 16) as Biomarkers of Lung Damage in COVID-19 Survivors: Literature Review

&lt;div&gt;&lt;table cellspacing="0" cellpadding="0" align="left"&gt;&lt;tbody&gt;&lt;tr&gt;&lt;td align="left" valign="top"&gt;&lt;p&gt;&lt;em&gt;CC16 or Clara cell secretory protein-16 is a protein produced from the secretion of respiratory epithelial club cells, especially in the lungs. &lt;/em&gt;&lt;em&gt;CC16 in several studies has anti-inflammatory effects and plays an important role in potential biomarkers and pathogenesis of chronic lung damage. One of the main respiratory diseases that attacks the lungs is COVID-19 (Coronavirus disease 2019). COVID-19 survivors had significantly decreased serum CC16 levels.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The purpose of this review is to draw conclusions based on findings based on research results on the potential of CC16 as a biomarker of lung damage in COVID-19 survivors.&lt;/em&gt;&lt;em&gt; This&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;research&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;used&lt;/em&gt;&lt;em&gt; a literature review of research &lt;/em&gt;&lt;em&gt;published&lt;/em&gt;&lt;em&gt; from 2019-2023 in electronic media&lt;/em&gt;&lt;em&gt;, &lt;/em&gt;&lt;em&gt;such as ProQuest, Science Direct, CINAHL, and Pubmed. The number of Randomized controlled trials (RCTs) research articles obtained was &lt;/em&gt;&lt;em&gt;seven&lt;/em&gt;&lt;em&gt; articles that met the criteria. The&lt;/em&gt;&lt;em&gt; research&lt;/em&gt;&lt;em&gt; subjects of the study &lt;/em&gt;&lt;em&gt;involved&lt;/em&gt;&lt;em&gt; COVID-19 survivors. The keywords used Clara cell secretory protein-16 (CC16), a biomarker of lung damage, and COVID-19 survivor. They &lt;/em&gt;&lt;em&gt;revealed&lt;/em&gt;&lt;em&gt; that serum CC16 levels were &lt;/em&gt;&lt;em&gt;found&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;to be a potential damage or biomarker of lung disease in COVID-19 survivors. This review concluded that CC16's structure and the possible formation of mechanisms &lt;/em&gt;&lt;em&gt;m&lt;/em&gt;&lt;em&gt;olecular and cellular can inhibit inflammation and in clinical applications are thought to be potential biomarkers and therapeutic targets of respiratory disease or chronic lung damage&lt;/em&gt;&lt;em&gt;. &lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;Future research &lt;/em&gt;&lt;em&gt;is required to&lt;/em&gt;&lt;em&gt; investigat&lt;/em&gt;&lt;em&gt;e&lt;/em&gt;&lt;em&gt; this hemoprotein in &lt;/em&gt;&lt;em&gt;the &lt;/em&gt;&lt;em&gt;circulation &lt;/em&gt;&lt;em&gt;of&lt;/em&gt;&lt;em&gt; COVID-19 survivors.&lt;/em&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/tbody&gt;&lt;/table&gt;&lt;/div&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Keywords: &lt;/em&gt;&lt;/strong&gt;&lt;strong&gt;&lt;em&gt; Biomarker, CC16, COVID-19 survivors, Clara cell protein-16&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt;

Driving pressure-guided ventilation improves homogeneity in lung gas distribution for gynecological laparoscopy: a randomized controlled trial

To investigate whether driving pressure–guided ventilation could contribute to a more homogeneous distribution in the lung for gynecological laparoscopy. Chinese patients were randomized, after pneumoperitoneum, to receive either positive end expiratory pressure (PEEP) of 5 cm H2O (control group), or individualized PEEP producing the lowest driving pressure (titration group). Ventilation homogeneity is quantified as the global inhomogeneity (GI) index based on electrical impedance tomography, with a lower index implying more homogeneous ventilation. The perioperative arterial oxygenation index and respiratory system mechanics were also recorded. Blood samples were collected for lung injury biomarkers including interleukin-10, neutrophil elastase, and Clara Cell protein-16. A total of 48 patients were included for analysis. We observed a significant increase in the GI index immediately after tracheal extubation compared to preinduction in the control group (p = 0.040) but not in the titration group (p = 0.279). Furthermore, the GI index was obviously lower in the titration group than in the control group [0.390 (0.066) vs 0.460 (0.074), p = 0.0012]. The oxygenation index and respiratory compliance were significantly higher in the titration group than in the control group. No significant differences in biomarkers or hemodynamics were detected between the two groups. Driving pressure–guided PEEP led to more homogeneous ventilation, as well as improved gas exchange and respiratory compliance for patients undergoing gynecological laparoscopy.Trial Registration: ClinicalTrials.gov NCT04374162; first registration on 05/05/2020.

Different levels of mucus inflammatory mediators in nasal polyposis with and without aeroallergen sensitivity.

ObjectivesBiomarker levels in nasal secretions can reflect the inflammatory status of nasal mucosa and evolution of sinus disease. The aim of this study was to evaluate the relationship between local inflammatory mediator production and clinical characteristics of patients with nasal polyposis (NP).MethodsThirty‐one nonaeroallergen sensitized patients with NP (NANP), 29 aeroallergen sensitized patients with NP (ANP), and 30 subjects without inflammation of nasal mucosa as controls (C) entered this prospective, cross‐sectional study. Clinical parameters (symptoms, endoscopic, and radiological findings) were assessed. The concentrations of heat shock protein 70 (HSP70), eosinophil cationic protein (ECP), tryptase, substance P and Clara cell protein 16 (CC16) were measured in the nasal secretion samples of all participants by ELISA method.ResultsOur results showed higher concentrations of HSP70, ECP, and tryptase in ANP than in NANP and C (p < .001 for all markers). On the other hand, levels of CC16 were significantly higher in C than in NANP and ANP groups (p < .001; p < .001, respectively). We found positive correlations between HSP70, ECP, tryptase, and substance P levels and nasal symptom score in patients with NP. Also, HSP70, ECP, tryptase, and substance P showed different levels of positive correlation among themselves, with HSP70 showing highest positive correlation with ECP. Finally, relatively strong negative correlations were found between the levels of CC16 and nasal symptoms, as well as between the CC16 levels and levels of other four mediators in nasal fluid.ConclusionHSP70, ECP, tryptase, and substance P might play a role in the pathogenesis of NP. The results suggest that chronic inflammation in NP involves a self‐sustaining local release of HSP70, ECP, and tryptase, independent of aeroallergen stimulation of the mucosal layer, although the production of these mediators is higher in aeroallergen sensitized NP patients.

Взаимосвязь альвеолярно-бронхиолярных нарушений с уровнем интерлейкина-20 у больных с внебольничной пневмонией

Objective is to study the relationship between clinical, laboratory and radiological manifestations of alveolar-bronchiolar dysfunction with the production of interleukin-20 in patients with community-acquired pneumonia. Materials and methods. We examined 60 patients of both sexes aged 18 to 45 years with bacterial community-acquired pneumonia in the first 3 days of the disease, as well as 15 practically healthy individuals. The material of the study was venous blood, in the serum of which the concentration of interleukins (IL) was determined: IL-1β, -2, -4, -8, -10, -17A, -20, -28A, -33, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), Clara cell protein (CCP), surfactant protein D (SP-D), prostacyclin (PgI2), soluble form of the Fas-receptor (sFas), and its ligand (sFasL), leukotriene D4 (LTD4), thromboxane A2 (TA2). Results. The development of pneumonia is accompanied by an increase in the production of the studied mediators, which is more pronounced in patients with a severe course of the disease. An increase in the concentration of IL-20 from the minimum to the maximum level is accompanied by a significant proportional decrease in the concentration of IL-1β, TNFα, IL-33, TA2, LTD4, Fas, FasL. A high level of IL-20 was associated with a decrease in the concentration of CCP, indicating a weakening of the alveolar-bronchiolar dysfunction and a decrease in the intensity of the inflammatory reaction in the lung tissue. It was also found that a high level of IL-20 was associated with increased production of PgI2, IFNγ, IL-1RA, IL-17A, IL-8, IL-4, IL-28A, IL-10, SLPI. Conclusion. The results of the study indicate the important role of IL-20 in the development of inflammation of the lower respiratory tract, which consists in regulating the activity of the acute phase response, modulating the production of prostacyclin and leukotrienes, determining the limitation of alveolar-bronchiolar dysfunction in patients with pneumonia, as well as the restriction of proapoptogenic influences that determine the decrease in volumes. tissue and cellular damage in such patients.

Correlations of Serum 1,25-Hydroxy Vitamin D3 level with Severity and Prognosis of Neonatal Respiratory Distress Syndrome.

This study was done to explore the correlations of serum 1,25-hydroxy vitamin D3 [1,25-(OH)2-VitD3] level with severity and prognosis of neonatal respiratory distress syndrome (NRDS). The clinical data of 145 NRDS children admitted between April 2019 and June 2020 were retrospectively analyzed. The subjects were comprised of 76 boys and 69 girls. Based on NRDS severity, they were assigned into mild group (n = 82) and severe group (n = 63), and their general data were compared. The independent factors affecting NRDS severity were evaluated by multivariate logistic regression analysis. The correlations of serum 1,25-(OH)2-VitD3 level in NRDS children with NRDS severity and other related blood test indices were analyzed using Spearman's and Pearson's methods. On the basis of multivariate analysis results, a prediction model was established using R3.6.0 software, which was validated by the receiver operating characteristic (ROC) curve and consistency index. The association between serum 1,25-(OH)2-VitD3 level and prognosis was evaluated through Kaplan-Meier curve. The severe group had higher groups of children with a gestational age < 39 weeks, spontaneous delivery, selective cesarean section, intrauterine distress, intrauterine infection, maternal hypertension, maternal dyslipidemia, and older maternal age than the mild group (p < 0.05). Procalcitonin, C-reactive protein, activin-A, Clara cell protein-16, interleukin-18, and IL-10 were significantly higher in the severe group than those in the mild group (p < 0.05), while serum bicarbonate, 1,25-(OH)2-VitD3, vitamin A, and IL-8 were significantly lower in the severe group than those in the mild group (p < 0.05). Multivariate logistic regression analysis results exhibited that gestational age < 39 weeks, lower 1,25-(OH)2-VitD3 and vitamin A levels, higher activin-A and CC-16 were independent risk factors for severe NRDS (p < 0.05). ROC curve analysis revealed that the area under the ROC curve of the model was 0.785, and the prediction accuracy was 88.08%. Serum 1,25-(OH)2-VitD3 level was significantly negatively correlated with NRDS severity (r = -0.287, p < 0.001), activin-A (r = -0.073, p < 0.001), and CC-16 (r = -0.098, p < 0.001), but positively correlated with vitamin A (r = 0.009, p < 0.001). Kaplan-Meier curve revealed that the survival rate of NRDS children with a high 1,25-(OH)2-VitD3 level was significantly higher than that of children with a low 1,25-(OH)2-VitD3 level (p < 0.001). 1,25-(OH)2-VitD3 is an independent influencing factor for the severity of NRDS and may affect the prognosis of NRDS children.

Association between the IL-6 polymorphisms and coal workers’ pneumoconiosis in a Chinese Hui population

ObjectiveTo determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.IntroductionGenes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.MethodsWe genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.ResultsCarrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP ( p &lt; 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects ( p &gt; 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.ConclusionsTaking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.

Refractory ceramic fibers induced changes in serum Clara cell protein 16 and surfactant protein D levels in rats

Objective: To explore the effect of refractory ceramic fibers (RCFs) on the serum Clara cell protein 16 (CC16) and surfactant protein D (SP-D) levels in Wistar rats. Methods: In October 2020, 96 healthy adult male Wistar rats were randomly divided into control group (equal volume of normal saline) , low-dose group (5 mg/ml RCFs) , medium-dose group (10 mg/ml RCFs) and high-dose group (20 mg/ml RCFs) , and subjected to non-exposure tracheal instillation. After intraperitoneal anesthesia, the rats were instilled with 200 μl of RCFs suspension or normal saline, once every 3 days for a total of 4 times. At 7, 14, 28, and 90 days after exposure, 6 rats were sacrificed by blood sampling through the abdominal aorta. The organs were separated, histopathological changes of lungs were observed and lung injury scores were performed. The contents of serum CC16 and SP-D were determined by enzyme-linked immunosorbent assay (ELISA) . Results: RCFs could cause inflammatory cells in rat lung tissues, widening of the lung septum and destruction of alveolar structure. 7 days after exposure, the lung injury scores of rats in each dose group were higher than control group, and the lung injury score of the high-dose group was higher than low-dose group (P<0.05) . 14 and 90 days after exposure, the lung injury scores of the medium-dose and high-dose groups were higher than control group (P<0.05) . 28 days after exposure, the lung injury score of the high-dose group was higher than control group (P<0.05) . 7 days after exposure, the serum CC16 and SP-D concentrations of rats in the medium-dose and high-dose groups were significantly higher than control and low-dose groups (P<0.05) . 28 days after exposure, the serum CC16 concentrations of rats in the low-dose and medium-dose groups were significantly lower than those of the control and high-dose groups (P<0.05) . After 90 days of exposure, the serum CC16 concentrations of rats decreased with the increase of the exposure dose (F=28.853, P<0.01) , and the concentrations of SP-D increased with the increase of the exposure dose (F=25.636, P<0.01) . Conclusion: RCFs exposure may cause certain damage to rat Clara cells and alveolar-capillary barrier. The severity of lung injury can be indirectly understood through the dynamic changes of serum CC16 and SP-D.

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection.

Gram-negative (G-) bacteria are the leading cause of hospital-acquired pneumonia in the United States. The devastating damage caused by G- bacteria results from the imbalance of bactericidal effects and overwhelming inflammation. Despite decades of research, the underlying mechanisms by which runaway inflammation is developed remain incompletely understood. Clara Cell Protein 16 (CC16), also known as uteroglobin, is the major protein secreted by Clara cells and the most abundant protein in bronchoalveolar lavage fluid (BALF). However, the regulation and functions of CC16 during G- bacterial infection are unknown. In this study, we aimed to assess the regulation of CC16 in response to Klebsiella pneumoniae (K. pneu) and to investigate the role of CC16 in bronchial epithelial cells. After K. pneu infection, we found that CC16 mRNA expression was significantly decreased in bronchial epithelial cells. Our data also showed that K. pneu infection upregulated cytokine and chemokine genes, including IL-1β, IL-6, and IL-8 in BEAS-2B cells. Endogenously overexpressed CC16 in BEAS-2B cells provided an anti-inflammatory effect by reducing these markers. We also observed that endogenous CC16 can repress NF-κB reporter activity. In contrast, the recombinant CC16 (rCC16) did not show an anti-inflammatory effect in K. pneu-infected cells or suppression of NF-κB promoter activity. Moreover, the overexpression of CC16 reduced reactive oxygen species (ROS) levels and protected BEAS-2B cells from K. pneu-induced apoptosis.

The interaction effect of aerobic exercise and vitamin D supplementation on inflammatory factors, anti-inflammatory proteins, and lung function in male smokers: a randomized controlled trial

BackgroundThis study aimed to investigate the interaction effect of aerobic exercise and vitamin D supplementation on inflammation (TNF-α, IL-6, CC16, SP-D, and CC16/SP-D ratio) and lung function (FEV1, FVC, and FEV1/FVC ratio) in male smokers.MethodsAfter applying inclusion criteria, a total of 40 healthy male smokers were recruited in this study. The participants were randomly divided into four groups as follows: Aerobic Exercise + vitamin D Supplementation (AE + VitD, n = 10), Aerobic Exercise (AE, n = 10), vitamin D Supplementation (VitD, n = 10), and Control (C, n = 10). The participants in the AE + VitD and AE groups performed aerobic exercise training (running) up to 50% of the maximum heart rate, three times a week for four weeks. Participants in AE + VitD and VitD groups received 6000 IU/w vitamin D3 for four weeks. The participants in control group did not receive any intervention. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, Clara cell protein (CC16), surfactant protein (SP)-D, CC16/SP-D ratio, and lung function (FEV1, FVC, and FEV1/FVC ratio) were measured before and after four weeks of intervention.ResultsSerum levels of TNF-α, IL-6, and CC16 decreased significantly in AE + VitD, VitD, and AE groups after four weeks (P < 0.05). Serum SP-D level decreased significantly only in the AE + VitD group (P = 0.011). In addition, FEV1 and FVC increased significantly (P < 0.05) in AE + VitD and AE groups after four weeks of intervention. However, the interventions did not have a significant effect on CC16/SP-D ratio and FEV1/FVC ratio (P > 0.05). Furthermore, serum levels of 1,25-dihydroxyvitamin D increased significantly in AE + VitD and VitD groups (P < 0.05) after four weeks of intervention. However, except for TNF-α, between-group comparisons showed no significant differences in levels of IL-6, CC16, SP-D, CC16/SP-D ratio, FEV1, FVC, FEV1/FVC, and 1,25-dihydroxyvitamin D (P > 0.05).ConclusionsThe results of present study were that aerobic exercise combined with vitamin D supplementation can reduce serum inflammatory factors and anti-inflammatory proteins and improve lung function after four weeks of intervention. Further trials with larger sample size and longer duration are suggested to confirm these results.Trial registration Retrospectively registered. IRCT20180513039637N4. Registration date: 2020/10/20. URL: https://www.irct.ir/search/result?query=IRCT20180513039637N4

Firefighters and COVID-19: An Occupational Health Perspective.

Firefighters and COVID-19: An Occupational Health Perspective.

Measurement of Tryptase and CC16/Albumin in Nasal Lavage Fluid as a Screening Tool of Allergic Rhinitis.

There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio. This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool. Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay. Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% (p = 0.013). The combination of "tryptase or CC16-to-albumin" could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.

Adipose-derived mesenchymal stem cells ameliorate lung epithelial injury through mitigating of oxidative stress in mustard lung.

Aim: We investigated potential efficacy of autologous adipose-derived mesenchymal stem cell (MSC) on oxidative stress (OS) and airway remodeling in patients with chronic mustard lung. Patients & methods: Ten patients received 100× 106 cells every 20days for 4 injections over a 2-month period. Results: A gradual improvement was observed for 6min walk test scores, pulmonary function tests and respiratory quality after MSCs therapy. A significant decrease was found for the mean levels of Mucin-1 protein (KL-6;p=0.022) and Clara cell protein 16 (CC16;p=0.005). Antioxidants had a tendency to be higher after each injection. Conclusion: Our findings revealed that MSCs therapy can be safely used for improvement of lung injury and regeneration in these patients without adverse effects. Trial registration number: NCT02749448 (ClinicalTrials.gov).

Serum Clara cell secretory protein (CC-16) in non-smoking patients with obstructive sleep apnea.

This study aimed to determine the association between the severity of obstructive sleep apnea (OSA) and serum Clara cell protein (CC16) levels in non-smoking patients with OSA. This prospective study included non-smoking patients who presented with sleep-related disturbances and underwent polysomnography (PSG). The serum CC16 level was measured and its relationship to PSG parameters was investigated. The study included 128 patients (83 men) with a mean age of 48.4 ± 11.9. OSA was detected in 66 men (70%) and 29 women (30%) (p = 0.051). The severity of OSA was mild in 32 (25%), moderate in 28 (22%), and severe in 35 (27%) of the patients. There was no significant difference in CC16 levels between the OSA group (1746 ± 1006) and the OSA negative group (1721 ± 1201, p = 0.91) levels. There was no significant difference between the CC16 levels of the each four groups. Mean serum CC16 levels were significantly lower in OSA negative men than OSA positive men (777 vs 1462, p = 0.005). No significant difference was observed in CC16 values according to OSA severity in women. The serum CC16 level does not differ between non-smoking OSA patients and OSA negative patients.

Individualized lung protective ventilation vs. conventional ventilation during general anesthesia in laparoscopic total hysterectomy.

Laparoscopic total hysterectomy is performed by carbon dioxide insufflation, Trendelenburg position and mechanical ventilation of patients under general anesthesia. However, this may induce pulmonary atelectasis and/or hyperdistention of the lungs. Multiple studies have indicated that mechanical ventilation with the use of low tidal volumes, moderate positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers may improve post-operative outcomes. However, the benefits of an individualized level of PEEP have not been clearly established. In the present study, it was hypothesized that a moderate fixed PEEP may not suit all patients and an individually-titrated PEEP during anesthesia may improve the peri-operative pulmonary oxygenation function. The aim of the present study was to compare the pulmonary oxygenation function and post-operative pulmonary complications (PPCs) in patients receiving individualized lung-protective mechanical ventilation (LPV) vs. conventional ventilation (CV) during laparoscopic total hysterectomy. The present study was a randomized double-blinded clinical trial on 87 patients who were randomly divided to receive CV or protective ventilation (PV). An optimal individualized PEEP value was determined using a static pulmonary compliance-directed PEEP titration procedure. Pulmonary oxygenation function, serum inflammatory factors, including interleukin-8 and Clara cell protein 16, the incidence of PPCs and the post-operative length of stay were also determined. Patients in the PV group exhibited improved pulmonary oxygenation function during and after the operation. The total percentage of PPCs during the first 7 days after surgery was significantly lower in the PV group compared with those in the CV group. In conclusion, as compared to CV, intra-operative individualized LPV significantly improved pulmonary oxygenation function and reduced the incidence of PPCs during the first 7 days after laparoscopic total hysterectomy (Clinical trial registration no. ChiCTR1900027738).