Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

Expression and Significance of Survivin mRNA in Lung Cancer of Different Progression Stages by FISH and Tissue Microarray Technology*

Objective： To investigate the expression of Survivin mRNA in lung cancer progression tissue microarray by FISH （fluorescence in situ hybridization） method and determine its role and significance in lung cancer genesis and progress. Methods： The expression of Survivin mRNA was detected by FISH method and tissue microarray technology. 89 cases of primary lung cancer, 12 cases of lymph node metastasis of lung cancer, 12 cases of precancerous lesion and 10 cases of normal lung tissue were examined. Results： 69.7% of primary lung cancer express Survivin mRNA; the positive ratio of primary lung cancer and precancerous lesion were both significantly higher than that of normal lung tissue （P〈0.05）; the expression of Survivin mRNA was related to the differentiation degree, lymph node metastasis and clinical stages （P〈0.05）. Conclusion： FISH has good sensitivity and stability. Tissue microarray technology has many advantages, such as high efficiency, high throughput, etc; it may have good prospect in pathology. Survivin mRNA was highly expressed in lung cancer and precancerous lesion; it was related to the progress and malignant behavior; it may play a promotion role in lung cancer genesis and progress and offer basis to early diagnosis, prognosis estimate and treatment.

EXPRESSION OF SURVIVIN,PTEN AND BFGF IN LUNG CANCER PROGRESSION TISSUE MICROARRAY

To investigate the expressions of survivin, PTEN and bFGF in lung cancer and precancerous lesion by tissue microarray technology. Methods: The expressions of Survivin, PTEN and bFGF were detected in 89 primary lung cancers, 12 lung cancers with lymph node metastasis, 12 precancerous lesions of lung by an immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expression of Survivin and bFGF protein were 57.3% and 66.3% in 89 primary lung cancer respectively, significantly higher than the control group (P<0.05). The positive ratio of PTEN was 42.7% in primary lung cancer, significantly lower than that of nornmal tissue (90.0%)(P<0.05). The expressions of Survivin and bFGF were significantly related to lymph node metastasis and clinical stages. The expression of PTEN was related to differentiations, lymph node metastasis and clinical stages (P<0.05). There was a negative correlation between expressions of Survivin and PTEN, a positive correlation between expressions of Survivin and bGFG (P<0.01). Conclusion: Survivin, PTEN and bFGF proteins may be related to the pathogenesis, progression and malignant behavious of lung cancer, and there are some relationships between expressions of Survivin, PTEN and bFGF. Survivin, PTEN and bFGF may play a role in prognosis assessment of lung cancer.

Lung tissue flap repairs esophagus defection with an inner chitosan tube stent

AIM： TO repair the partial esophagus defect with a chitosan stent, a new esophageal prosthesis made of pulmonary tissue with vascular pedicie.METHODS： Fifteen Japanese big ear white rabbits were divided into experimental group （n = 10） and control group （n = 5）. Esophagus defect in rabbits of experimental group was repaired using lung tissue flap with a chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation. Esophagus defect of rabbits in control group was repaired using lung tissue flap with no chitosan tube stent, gross and histological appearance was observed at week 2, 4 and 8 after operation, and barium sulphate X-ray screen was performed at week 10 after operation.RESULTS： In the experimental group, 6 rabbits survived for over two weeks, the lung tissue flap healed esophageal defection, and squamous metaplasia occurred on the surface of lung tissue flap. At week 10 after operation, barium sulphate examination found that barium was fluent through the esophagus with no stricture or back stream, the creeping was good. In the control group, 4 rabbits survived for two weeks, the lung tissue flap healed esophageal defection with fibrous tissue hyperplasia, barium sulphate examination found that barium was fluent through the esophagus with a slight stricture or back stream, and the creeping was not good at week 10 after operation.CONCLUSION： Esophagus defect can be repaired using lung tissue flap with an inner chitosan tube stent.

Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

Objective： To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods： Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis （2-DE） and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Results： （1） Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; （2） A total of 1178±56 spots were matched between the eleetrophoretie maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; （3） Sixty-eight differential proteins were identified by PMF, some proteins were the products of oneogenes, and others involved in the regulation of cell cycle and signal transduetion; （4） In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung squamous carcinoma, was detected by immunohistoehemieal staining and Western blot analysis. The results revealed that mdm2, c-jun and EGFR were up-regulated in lung squamous carcinomas, whereas they were down-regulated in adjacent normal bronchial epithelial tissues, normal lung tissues and inflammatory pseudotumor, which was consistent with our proteome analysis results. Conclusion： The well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were established and 68 differential proteins were characterized by applying comparative proteome analysis successfully. These results will provide scientific foundation for screening the molecular biomarker used to diagnose and treat lung squamous carcinoma, as well as to improve the patient＇s prognosis and provide new clue for the research of lung squamous carcinogenic mechanism.

EXPRESSION AND SIGNIFICANCE OF SURVIVIN mRNA IN LUNG CANCER TISSUE MICROARRAY DETECTED BY FISH

Objective To investigate the expression of Survivin mRNA in lung cancer tissue microarray （TMA） by fluorescence in .situ hybridization （FISH） method, and determine the role and significance of it in lung cancer genesis and progress. Methods The expression of Survivin mRNA was detected by FISH method and TMA technology. Fifty-four cases of lung cancer and 10 cases of normal lung tissue were examined. Survivin mRNA was expressed in 66.7% （36/54） of lung cancer; the positive ratio of lung cancer was significantly higher than that of normal lung tissue （0/10;X^2= 15.238, P 〈 0.05）. The positive ratio of Survivin mRNA was significantly higher in poor differentiated cancer （20/24, 83.3% ） than moderate and well differentiated cancer （16/30, 53.3%; X^2 = 5.40, P 〈 0.05）. The positive ratio of Survivin mRNA was significantly higher in group with lymph node metastasis （27/32, 84.4%） than without lymph node metastasis （9/22, 40.9%; X^2= 11.084, P 〈 0.05）. The positive ratio of Survivin mRNA was significantly higher in stage Ⅲ-Ⅳ（12/13, 92.3%） than stage Ⅰ- Ⅱ （24/41,58.5%; X^2=5.066, P〈 0.05）. Conclusion Survivin mRNA highly expresses in lung cancer, which is related to the progress and malignant behavior. Survivin may play a promoting role in lung cancer genesis and progress and provide a basis for estimating prognosis and treatment.

Sparing lung tissue with virtual block method in VMAT planning for locally advanced non-small cell lung cancer

This study aimed to exploit a new virtual block method to spare normal lung tissue in VMAT planning for patients with locally advanced non-small cell lung cancer(LA-NSCLC).The previous method was used to manually restrict the angle of the beam passing through,which ignored the location and shape of large targets that varied between different slices and did not block the beamlets precisely.Unlike the previous method,this new virtual block method was used to block the beamlets when necessary by closing the multi-leaf collimator(MLC)at prerequisite angles.The algorithm for closing the MLC depended on the thickness of the beamlets passing through the lungs and avoided only the entrance radiation beamlet.Moreover,this block can be automatically contoured.A retrospective study was performed to compare the VMAT plans with and without the virtual block method for 17 LANSCLC patients,named the block plan(B-plan)/non-block plan(N-plan).All cases were selected in this study because of the large tumor size and unmet dose constraints of the lungs.In addition to the maximum dose constraint for the virtual block,B-plans adopted identical optimization parameters to N-plans for each patient.These two types of plans were compared in terms of dosimetric indices and plan scores.The results were statistically analyzed using the Wilcoxon nonparametric signed-rank test.B-plans have advantages in the following dosimetric metrics that have statistical significance(p<0.05):(1)lower V_(5)/V_(10)/D_(mean)/normal tissue complication probability(NTCP)of total lungs;(2)reductions in V_(5)/V_(10)for the contralateral lung;(3)decrease in Dmean/V_(40)of the heart;(4)decrease in esophagus V_(40);(5)reductions in Dmean,V_(5)/V_(10) of normal tissue.B-plans(82.51±7.07)achieved higher-quality scores than N-plans(80.74±7.22).The new virtual block spared the lungs as well as other normal structures in VMAT planning for LA-NSCLC.Thus,the block method may decrease the risk of radiation-related toxicity in patients.

Expression of Peroxiredoxins and Pulmonary Surfactant Protein A Induced by Silica in Rat Lung Tissue

Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities.

INFLUENCE OF ZINC，MANGANESE AND SELENIUM ONSUPEROXIDE DISMUTASE ACTIVITY IN LUNGCANCER TISSUE AND CELL IN CULTURE

In this experiment,the cancer tissues and cells,Which were derived from Lewis lung cancer and A549 lung Cancer cell line,were respectively divided into four groups and zinc, manganese and selenium were respectively added to the medium for 24 hours. The superoxide dismutase activity in the tissues and the cells was estimated. It was found that the SOD activity was enhanced by zinc and manganese and the effect of zinc on SOD activity was superior to that of manganese. We supposed that the enhance of the SOD activity was relative to the activation of the SOD apoenzymes. This experimental result indicated that the inhibitory effect of zinc and manganese on carcinogenesis was achieved by SOD and the elements might be considered a SOD activator.

DETECTING EXPRESSION OF MRP-1/CD9 mRNA IN LUNG CANCERS USING TISSUE MICROARRAYS AND FLUORESCENCE IN SITU HYBRIDIZATION METHODS

Objective： The aim of this study was to investigate the MRP-1/CD9mRNA expression in lung cancer and normal lung tissues and the relationship between its expression and pathologic grades, clinical stages, metastasis and prognosis. Methods： To observe MRP-1/C9mRNA expression, tissue microarray （TMA） containing 54 lung cancers and 10 normal lung tissues was prepared and Fluorescence in situ hybridization was used. Results： The positive rate of MRP-1/CD9 expression was 48.1% in lung cancer, lower than that of normal lung tissues. The statistical difference was significant （P〈0.05）. Its protein expression had no relationship with the patients＇ ages, sex and the macroscopic type of tumor, but had relationships with the histological type, clinical stage, differentiated degree and metastasis. The expression in non-small cell lung cancer （NSCLC） was higher than that in small cell lung cancer （SCLC）; in well-moderately differentiated group was higher than that in poorly differentiated group; Earlier period group （I＋II） was higher than in later period group （Ⅲ＋Ⅳ）; and in group without lymphoid metastasis was higher than in patients with lymphoid metastasis. Conclusion： The progression of the lung cancer maybe related with the descended MRP-1/Cd9 expression, which may be useful in evaluating the prognosis of cancer patients.

The Differences of Interstitial Lung Diseases in High-Resolution Computerized Tomography and Pulmonary Function Test among Different Connective Tissue Diseases, and the Correlated Factors

Objective. To study the difference of interstitial lung diseases (ILDs) in high-resolution computerized tomography and pulmonary function test among different connective tissue diseases (CTDs). Methods. 209 patients with different CTDs were recruited and underwent lung HRCT and PFT. Eerythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin (SF), anti-SSA, and so on were tested. Based on HRCT, a patient was classified into ILD group (CTD+ILD) or non-ILD group (CTD-ILD). HRCT, PFT, and laboratory markers were compared according to CTDs and CTD-associated ILDs. Results. The incidences of ILD were 79.6%, 82.0%, 89.7%, and 97.1% respectively for Rheumatoid arthritis (RA), primary Sjogren’s symptom (pSS), dermatomyositis/polymyositis (DM/PM), and systemic sclerosis (SSc) groups. RA and pSS patients exhibited more nodules, patching, ground-glass opacity, and cord shadow foci in HRCT, DM/PM and SSc patients exhibited more reticular opacity and honeycombing foci. RA and pSS patients exhibited more obstructive ventilatory disorder, small airway dysfunction and emphysema in PFT, and DM/PM and SSc patients exhibited more restrictive ventilatory disorder, mixed ventilatory disorder. ESR, CRP and SF were significantly higher in total CTD+ILD group than in total CTD-ILD group (P = 0.047, 0.006, 0.004, respectively), and higher in different CTD+ ILD groups than in comparable CTD-ILD groups (P = 0.049, 0.048, and 0.023, pSS+ILD, SSc+ILD and RA+ILD compared to pSS-ILD, SSc-ILD and RA-ILD, respectively for ESR, CRP, SF). The positive rate of anti-SSA was significantly higher in DM/PM+ILD group than in DM/PM-ILD group (P = 0.025). Conclusions. The manifestations and incidences of ILDs differ among different CTDs in HRCT and PFT, and inflammation and anti-SSA are positively correlated with ILDs in different CTDs, which provide important evidences for judging disease condition and prognosis.

Reliability of a Tissue Microarray in Detecting Thyroid Transcription Factor-1 Protein in Lung Carcinomas

OBJECTIVE To compare the expression of the thyroid transcription factor-1 （TTF-1） in human normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and cancer cells of lung carcinoma and metastatic lymph nodes using a tissue microarray （TMA） along with paired conventional full sections, and to investigate the reliability of tissue microarrays in detecting protein expression in lung carcinoma. METHODS A lung carcinoma TMA including 765 cores was constructed. TTF-1 protein expression in both TMA and paired conventional full sections were detected by the immunohistochemical SP method using a monoclonal antibody to TTF-1. A PU （Positive Unit） of TTF-1 protein was assessed quantitatively by the Leica Q500MC image analysis system with results from the paired conventional full sections as controls. RESULTS There was no significance between TMA and paired conventional full sections in TTF-1 expression in different nuclei of the lung tissue. CONCLUSION TTF-1 protein expression in lung carcinoma detected by TMA was highly concordant with that of paired full sections. TMA is a reliable method in detecting protein expression.

Expression of Elk-1 in Non-Small Cell Lung Cancer Detected by Western Blot and Tissue Microarray

Objective： The aim of this study was to investigate the Elk-1 （Ets like transcription factor-1） expression in non-small cell lung cancer （NSCLC） and normal lung tissues and the relationship between its expression and clinicopathological characters. Methods： To observe Elk-1 expression, western blot and immunochemistry （IHC） on tissue microarray （TMA） containing 118 lung cancers and their corresponding normal tissues were used. Results： In western blot and IHC on TMA, Elk-1 was highly expressed in NSCLC, while its expression was almost undetectable in normal lung tissues. Elk- 1 expression in NSCLC had no relationship with the patients＇ age, gender, smoking status and histological type, but had relationship with the differentiation degree, clinical stages and lymphonode metastasis. The expression was lower in early stage group （Ⅰ＋Ⅱ） than in advanced stage group （Ⅲ）, and lower in well-moderately differentiated group than in poorly differentiated group. The same trend was seen with lymphonode metastasis. Conclusion： The progression of NSCLC may be related with the increased Elk-1 expression, and Elk-1 may be regarded as a prognostic factor for NSCLC tissues.

Biological Significance and the Related Molecular Mechanism of Ets1 mRNA Expression in Lung Cancer by Tissue Microarray(TMA)

Objective： To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray （TMA） method. Methods： The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH（fluorescence in situ hybridization） and immunohistochemical method, and 10 normal lung tissues were used as controls. Results： The expressions of Ets-1 rnRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group （P〈0.05）. The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins （P〈0.05）. Conclusion： Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.

Immunohistochemical Localization of Aspergillus and p53 in Human Lung Tissues

Aspergilli are filamentous fungi which can cause opportunistic infections in Acquired Immunodeficiency Syndrome (AIDS) patients. Aspergilli can be found in human tissues either in the form of spores or hyphae. p53 is a tumor suppressor gene located in the short arm of chromosome 17. It is a potent transcriptional regulator of genes which are involved in many cellular activities including cell cycle arrest, apoptosis and angiogenesis. A loss of tumor suppressor function of p53 is the most common event leading to the development of human cancers. The rate by which p53 has a homology between different species has been reported from human to other vertebrates, it has been reported that it is available within Drosophila melanogaster and C. elegans [1] [2]. The aim of this study is to check if p53 is localized within Aspergilli or not using immunohistochemical techniques and study the relationship between Aspergilli infection and p53 in human lung tissues. 45 different samples of lung tissues, diagnosed as being none tumor, were taken randomly during the year of 2003-2004 from the autopsy cases submitted to the forensic medicine center in Irbid, Jordan. The sample group consisted of 12 females and 33 males. Labeled Streptavidin Biotin (LSAB) method and Mach-4 method were used to determine the Aspergilli infection and p53. The results show that the Aspergillus is presented in all used samples (100% of the infection) in the form of spores or hyphae and all infected samples have mutant p53 molecules (p53 was located in Aspergillus spores and hyphae). According to this study, it is safe to posit that the mutant p53 molecules may be used by Aspergillus for its multiplication. Seemingly it is a biological behavior of Aspergillus to produce p53. The fate of the p53 is questioned, is it going to interact with the human cells initiating cancer? Further experimental investigations are required to determine such pathway. In conclusion, this study shows that Aspergillus is a producing agent for p53 and Aspergillus pathogenicity is caused by production of p53.

Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis:Two case reports

BACKGROUND Pulmonary cryptococcosis(PC)is an opportunistic infectious disease of the respiratory system.Lung tissue biopsies,culture of respiratory samples(e.g.,sputum,lung tissue,pleural fluid,and bronchoalveolar lavage fluid),and cryptococcal antigen(CrAg)testing are helpful for a definitive diagnosis.However,these tests are sometimes falsely negative.PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms,poor imaging specificity,and false-negative laboratory tests.CASE SUMMARY We report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis.In both patients,the CrAg test on the lung biopsy tissue homogenate was positive,while the serum CrAg test was negative.Combined with the lung tissue pathology,we made the diagnosis of PC.Antifungal therapy was effective in both patients.CONCLUSION Given the findings of our cases and the literature review,lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.

Evidence for a Non-<i>β</i>₂-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of <i>β</i>₂-Adrenoceptor Agonists

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the β2-AR.

Identification of p63 expression in human lung cancer: analysis by complementary DNA and tissue microarray

Objective: To evaluate p63 expression at mRNA transcripts and protein levels in lung squamous cell cancer (SCC), adenocarcinoma, large cell lung cancer (LCLC) and small cell lung cancer (SCLC) and their matched metastatic tumors. The association between p63 expression and p63 locus at chromosomal 3q27 q29 was also investigated. Methods: p63 mRNA expression levels in a large series of lung cancers including SCC, adenocarcinoma, LCLC, SCLC and their matched metastatic tumors were analyzed by cDNA microarray technology. A tissue microarray from 150 primary lung cancer specimens was constructed and used for immunohistochemical detection of p63 protein expression. Chromosomal imbalances at the p63 locus in 70 primary lung cancers samples were studied by comparative genomic hybridization (CGH) technology. Results: mRNA levels were 10 fold in SCC compared to LCLC, SCLC, and adenocarcinoma. Interestingly, the mRNA expression of p63 in metastatic carcinomas was significantly higher than that in their matched primary tumors ( P <0 001). Immunohistochemistry demonstrated that p63 expression was 94.64% in SCC but only 1 79% in lung adenocarcinoma and 2 of 4 LCLC were positive staining. All the results in of SCLC were negative. There was a statistically significant difference for p63 positivity between pT1 tumors and those of higher stage ( P =0 035). The CGH results indicated that p63 locus at chromosomal 3q27 q29 was overrepresented in SCC. p63 immunopositivity correlated significantly with pronounced gains of the p63 locus at chromosomal 3q27 q29 (P=0.0001), indicating that strong expression of p63 in lung SCC correlated with increased gene amplification. Conclusion: p63 might play an important role not only in squamous differentiation of lung cancer but also in tumor development and progression.

Interstitial Lung Diseases Associated with Connective Tissue Pathologies: Radiologic Features

Introduction: The high resolution computed tomography (HRCT) is an important part in the diagnostic approach of interstitial lung disease (ILD) associated with connective tissue diseases (CTD) by providing detailed information on the elementary lesion and the radiological pattern of ILD. Aim: to point out the role of HRCT in the diagnosis of ILD associated with CTD (ILD-CTD). Methods: A Retrospective descriptive study was conducted between 2008 and 2017. Data of 24 patients presenting ILD-CTD were collected. A review of HRCT was performed by a radiologist without knowledge of the CTD. Results: Predominant elementary lesion of ILD associated with dermatomyositis (9 cases) was ground glass opacity (n = 9) followed by consolidation (n = 6). Non Specific Interstitial Pneumonia (NSIP) was the most reported pattern (5 cases). Ground glass opacity was also the predominant elementary lesion for the 2 cases of scleroderma and in Sj&#246gren’s syndrome (4 cases/5). NSIP was the predominant radiological presentation in these two CTD. Lymphoid interstitial pneumonia revealed Sj&#246gren’s syndrome in one case. In rheumatoid arthritis (6 cases), the elementary HRCT lesions were irregular interlobular septal thickening (n = 4) and honeycombing (n = 4) consistent with Usual Interstitial Pneumonia (UIP) in 2 cases. Similarly UIP has been described for the 2 patients with lupus and mixed connective tissue disease. Conclusion: HRCT plays an important role in the management of ILD-CTD. Description of the HRCT elementary lesions and the radiological pattern of ILD can be helpful for CTD’s diagnosis.

High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1

BACKGROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical outcomes.AIM To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals.METHODS First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis.We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the colon.Next,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)axis.Finally,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways.RESULTS High-fat diet was found to aggravate TNBS-induced colitis in mice.The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased.The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway.This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p.CONCLUSION Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.