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We previously reported pulmonary arterial remodelling and active endothelial to mesenchymal transition (EndMT) in smokers and patients with early COPD. In this study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-ß1, pSMAD-2/3, SMAD-7, and ß-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-ß1 (p<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (p <0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared to NC. Total ß-catenin expression was significantly higher in smoking groups across arterial sizes (p <0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total ß-catenin was positively correlated with total S100A4 in small and medium arteries (r= 0.35, 0.50; p=0.02, 0.01, respectively), with vimentin in medium arteries (r=0.42, p=0.07), and with arterial thickness of medium and large arteries (r= 0.34, 0.41, p=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-ß1 in smokers, SAD, and COPD patients. Increased expression of ß-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway.
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Large airway wall lamina propria in patients with asthma-COPD overlap is hypovascular with an increase in reticular basement membrane neoangiogenesis, reflecting smoking-related COPD-like pathology and potential epithelial-to-mesenchymal transition https://bit.ly/49DeoFX.
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The improvement of dual-mode techniques was of particular interest to researchers, which might enhance the detection performance and applicability. Here, a dual-mode optical aptasensor (DO-aptasensor) platform based on exonuclease I (Exo I) cyclic digestion and synergistic enhancement strategy had proposed for zearalenone (ZEN). Following the preparation of dumbbell-shaped signal probe, the Exo I-based cyclic digestion amplification performed, and then the synergistic enhancement effect carried out to achieve the Poly-HRP-based colorimetry and FAM-SGI-based fluorescence. The efficient homogeneous system realized through the magnetic separation, while the signal interference further eliminated by the graphene oxide (GO). The LOD values were as low as 0.067 ng mL-1 for colorimetry mode and 0.009 ng mL-1 for fluorescence mode, which reduced 23-fold and 172-fold than ELASA by same ZEN-Apt. This promising platform gave rise to a dual-mode optical readout, improved sensitivity and positively correlated detection. Meanwhile, the DO-aptasensor also exhibited the acceptable specificity, desirable reliability and excellent practicability. This novel avenue of aptasensor platform hold great potential for dual-mode optical monitoring of other targets, which can further expand the application scope of Exo I-based signal amplification and synergistic enhancement effect.
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Background: The aim of our study was to administer adequate local anesthetic in programmed intermittent epidural bolus (PIEB) to avoid breakthrough pain and decrease the use of manual and PCEA boluses. We, therefore, conducted this study to determine the effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects (EI90), without the use of patient-controlled epidural analgesia (PCEA). Methods: A total of 80 subjects were included in the final statistical analysis from 23 August 2022 to 22 November 2022. The subjects were randomly assigned to one of four different PIEB time intervals: 40, 50, 60, and 70 min (groups 40, 50, 60, and 70), respectively. The primary outcome was the effective epidural labor analgesia, defined as no use of PCEA bolus or a manual bolus until the end of the first stage of labor or within 6 hours after loading dose administration. The PIEB EI90 (95% CI) between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL was estimated using probit regression. Results: The effective PIEB interval time between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL in 90% of subjects without the use of PCEA was 45.4 (35.5-50.5) minutes using probit regression. No statistical differences were found in the proportion of subjects with Bromage score > 0, hypotension, pruritus, nausea, and vomiting between groups. However, the highest sensory block (pinprick) in the 40-min group was significantly higher than that in the other groups. Conclusion: The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 µg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5-50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice.
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Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung fibrotic disorder of unknown cause. It has been reported that bacterial and viral co-infections exacerbate disease pathogenesis. These pathogens use adhesion molecules such as platelet activating factor receptor (PAFR) and intercellular adhesion molecule-1 (ICAM-1) to gain cellular entry, causing infections. Methods: Immunohistochemical staining was carried out for lung resections from IPF patients (n = 11) and normal controls (n = 12). The quantification of PAFR and ICAM-1 expression is presented as a percentage in the small airway epithelium. Also, type 2 pneumocytes and alveolar macrophages were counted as cells per mm2 of the parenchymal area and presented as a percentage. All image analysis was done using Image Pro Plus 7.0 software. Results: PAFR expression significantly increased in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Similar trend was observed for ICAM-1 expression in the small airway epithelium (p < 0.0001), type 2 pneumocytes (p < 0.0001) and alveolar macrophages (p < 0.0001) compared to normal controls. Furthermore, the proportion of positively expressed type 2 pneumocytes and alveolar macrophages was higher in IPF than in normal control. Conclusions: This is the first study to show PAFR and ICAM-1 expression in small airway epithelium, type 2 pneumocytes and alveolar macrophages in IPF. These findings could help intervene microbial impact and facilitate management of disease pathogenesis.
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Background: COPD patients suffer from dysregulated and suppressed immune functionality, determined by their loss of degranulating capacity. Here we provide crucial information on the presence of degranulated mast cells (MCs) in COPD airways and demonstrate their relationship to lung physiology and airway remodelling. Methods: Small airway lung resections from non-smoking controls (NC), normal lung function smokers (NLFS), small airway disease (SAD), and mild-to-moderate COPD current smokers (COPD-CS) and ex-smokers (COPD-ES) were dual immuno-stained with MC tryptase and degranulation marker lysosome-associated membrane protein (LAMP)-1. Total MCs, degranulating MCs and non-MCs were enumerated in small airway epithelium and subepithelium, and in alveolar septa. Results: In the small airway wall subepithelial areas, COPD-CS and COPD-ES patients had significantly lower MCs than the NC group (p<0.05), although the numbers were considerably higher in the small airway epithelium (p<0.01). Degranulating non-MCs were higher in SAD (p<0.05) than in COPD in the small airway subepithelium. In contrast, there were significant increases in total MCs (degranulated and non-degranulated) and degranulated non-MCs in the alveolar septum of COPD patients compared with the NC group (p<001). The lower numbers of MCs in the subepithelium correlated with lower forced expiratory volume in 1â s (FEV1)/forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (FEF25-75%), higher smoking rates in COPD patients, and increased small airway wall thickness and extracellular matrix. The increase in MCs in the alveolar septum negatively correlated with FEF25-75%. Conclusions: This study is the first to assess the differential pattern of MC, degranulating MC and non-MC populations in the small airways and alveoli of COPD patients. The spatial positioning of the MCs within the airways showed variable correlations with lung function.
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Background: We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to endothelial to mesenchymal transition (EndMT). In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD. Methods: Immunohistochemical staining for the EndMT biomarkers CD31, N-cadherin, vimentin and S100A4 was done on lung resection tissue from 49 subjects. These comprised 15 nonsmoker controls (NC), six normal lung function smokers (NLFS), nine patients with small airway disease (SAD), nine current smokers with mild-moderate COPD (COPD-CS) and 10 ex-smokers with COPD (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0. Results: We noted reduced junctional CD31+ endothelial cells (p<0.05) in the intimal layer of all smoking groups compared to NC. We also observed increased abundance of the mesenchymal markers N-cadherin (p<0.05) and vimentin (p<0.001) in all smoking groups and across all arterial sizes versus NC, except for N-cadherin in large arteries in COPD-CS. The abundance of S100A4 correlated with arterial thickness (small: r=0.29, p=0.05; medium: r=0.33, p=0.03; large: r=0.35, p=0.02). Vimentin in the small arterial wall negatively correlated with forced expiratory volume in 1â s/forced vital capacity (r=â¯-0.35, p=0.02) and forced expiratory flow rate at 25-75% of forced vital capacity (r=â¯-0.34, p=0.03), while increased cytoplasmic CD31 abundance in the intimal layer of medium and large arteries negatively correlated with predicted diffusing capacity of the lung for carbon monoxide (medium: r=â¯-0.35, p=0.04; large: r=â¯-0.39, p=0.03). Conclusion: This is the first study showing the acquisition of mesenchymal traits by pulmonary endothelial cells from NLFS, SAD and mild-moderate COPD patients through EndMT. This informs on the potential early origins of pulmonary hypertension in smokers and patients with early COPD.
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Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Methods: Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Results: Significant TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin expression was apparent across all arterial sizes in IPF (p < 0.05). Intimal TGF-ß1, pSmad-2/3, Smad-7, and ß-catenin were augmented in the arterial range of 100-1000 µm (p < 0.001) compared to NC. Intimal TGF-ß1 and ß-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, p = 0.05 and r' = 0.61, p = 0.02, respectively) and intimal N-cadherin (r' = 0.62, p = 0.03 and r' = 0.70, p = 0.001, respectively). Intimal TGF-ß1 and ß-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, p = 0.04; r' = 0.052, p = 0.04, respectively). Moreover, intimal TGF-ß1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, p = 0.002). Furthermore, total TGF-ß1 expression significantly impacted the percentage of DLCO (r' = -0.61, p = 0.03). Conclusions: This is the first study to illustrate the involvement of active TGF-ß/Smad-2/3-dependent and ß-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.
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Background: Epithelial-mesenchymal transition (EMT) might be central to lung cancer development in smokers and COPD. We illustrate EMT changes in a broader demographic of patient groups who were diagnosed with nonsmall cell lung cancer (adenocarcinoma and squamous cell carcinoma). These included COPD current and ex-smokers, patients with small airway disease and normal lung function smokers compared to normal controls. Methods: We had access to surgically resected small airway tissue from 46 subjects and assessed for airway wall thickness and immunohistochemically for the EMT biomarkers E-cadherin, N-cadherin, S100A4, vimentin and epidermal growth factor receptor (EGFR). All tissue analysis was done with a computer and microscope-assisted Image-Pro Plus 7.0 software. Results: Airway wall thickness significantly increased across all pathological groups (p<0.05) compared to normal controls. Small airway epithelial E-cadherin expression markedly decreased (p<0.01), and increases in N-cadherin, vimentin, S100A4 and EGFR expression were observed in all pathological groups compared to normal controls (p<0.01). Vimentin-positive cells in the reticular basement membrane, lamina propria and adventitia showed a similar trend to epithelium across all pathological groups (p<0.05); however, such changes were only observed in reticular basement membrane for S100A4 (p<0.05). Vimentin was higher in adenocarcinoma versus squamous cell carcinoma; in contrast, S100A4 was higher in the squamous cell carcinoma group. EGFR and N-cadherin expression in both phenotypes was markedly higher than E-cadherin, vimentin and S100A4 (p<0.0001). Conclusion: EMT is an active process in the small airway of smokers and COPD diagnosed with nonsmall cell lung cancer, contributing to small airway remodelling and cancer development as seen in these patients.
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BACKGROUND: Although asthma and chronic obstructive pulmonary disease (COPD) are two distinct chronic airway inflammatory diseases, they often co-exist in a patient and the condition is referred to as asthma-COPD overlap (ACO). Lack of evidence regarding the inflammatory cells in ACO airways has led to their poor prognosis and treatment. The objective of this endobronchial biopsy (EBB) study was to enumerate inflammatory cellular changes in the airway wall of ACO compared with asthma, COPD current smokers (CS) and ex-smokers (ES), normal lung function smokers (NLFS), and non-smoker controls (HC). METHODS: EBB tissues from 74 patients were immunohistochemically stained for macrophages, mast cells, eosinophils, neutrophils, CD8+ T-cells and CD4+ T-cells. The microscopic images of stained tissues were evaluated in the epithelium, reticular basement membrane (RBM) cells/mm RBM length, and lamina propria (LP) cells/mm2 up to a depth of 120 µM using the image analysis software Image-Pro Plus 7.0. The observer was blinded to the images and disease diagnosis. Statistical analysis was performed using GraphPad Prism v9. RESULTS: The tissue macrophages in ACO were substantially higher in the epithelium and RBM than in HC (P < 0.001 for both), COPD-ES (P < 0.001 for both), and -CS (P < 0.05 and < 0.0001, respectively). The ACO LP macrophages were significantly higher in number than COPD-CS (P < 0.05). The mast cell numbers in ACO were lower than in NLFS (P < 0.05) in the epithelium, lower than COPD (P < 0.05) and NLFS (P < 0.001) in RBM; and lower than HC (P < 0.05) in LP. We noted lower eosinophils in ACO LP than HC (P < 0.05) and the lowest neutrophils in both ACO and asthma. Furthermore, CD8+ T-cell numbers increased in the ACO RBM than HC (P < 0.05), COPD-ES (P < 0.05), and NLFS (P < 0.01); however, they were similar in number in epithelium and LP across groups. CD4+ T-cells remained lower in number across all regions and groups. CONCLUSION: These results suggest that the ACO airway tissue inflammatory cellular profile differed from the contributing diseases of asthma and COPD with a predominance of macrophages.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncoscopia , Biópsia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Asma/diagnóstico , PulmãoRESUMO
It was urgent to improve the intuitive, portable, sensitive and multi-modal detection method for small molecules. In this study, a tri-modal readout of plasmonic colorimetric immunosensor (PCIS) for small molecule (zearalenone, ZEN, as an example) had been established based on the Poly-HRP amplification and gold nanostars (AuNS) etching. The immobilized Poly-HRP from the competitive immunoassay was used to catalyze iodide (I-) into iodine (I2), which could prevent the AuNS etching by I-. With the increasing of ZEN, the AuNS etching was enhanced, and the localized surface plasmon resonance (LSPR) peak of AuNS showed stronger blue shift, which resulted in the color changing from deep blue (no-etching) to blue violet (half-etching) and finally to shiny red (all-etching). The results of PCIS could be selectively obtained by the tri-modal readout: (1) naked eye (LOD of 0.10 ng/mL), (2) smartphone (LOD of 0.07 ng/mL) and (3) UV-spectrum (LOD of 0.04 ng/mL). The proposed PCIS had performed well in the sensitivity, specificity, accuracy and reliability. In addition, the harmless reagents were used in the overall process to further guarantee the environmental friendliness. Therefore, the PCIS might provide a novel and green avenue for the tri-modal readout of ZEN via the intuitive naked eye, portable smartphone and accurate UV-spectrum, which hold great potential for small molecule monitoring.
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Background: COPD is a common disease characterized by respiratory airflow obstruction. TGF-ß1 and SMAD pathway is believed to play a role in COPD pathogenesis by driving epithelial mesenchymal transition (EMT). Methods: We investigated TGF-ß1 signalling and pSmad2/3 and Smad7 activity in resected small airway tissue from patients with; normal lung function and a smoking history (NLFS), current smokers and ex-smokers with COPD GOLD stage 1 and 2 (COPD-CS and COPD-ES) and compared these with normal non-smoking controls (NC). Using immunohistochemistry, we measured activity for these markers in the epithelium, basal epithelium, and reticular basement membrane (RBM). Tissue was also stained for EMT markers E-cadherin, S100A4 and vimentin. Results: The Staining of pSMAD2/3 was significantly increased in the epithelium, and RBM of all COPD groups compared to NC (p <0.0005). There was a less significant increase in COPD-ES basal cell numbers compared to NC (p= 0.02). SMAD7 staining showed a similar pattern (p <0.0001). All COPD group levels of TGF-ß1 in the epithelium, basal cells, and RBM cells were significantly lower than NC (p <0.0001). Ratio analysis showed a disproportionate increase in SMAD7 levels compared to pSMAD2/3 in NLFS, COPD-CS and COPD-ES. pSMAD negatively correlated with small airway calibre (FEF25-75%; p= 0.03 r= -0.36). EMT markers were active in the small airway epithelium of all the pathological groups compared to patients with COPD. Conclusion: Activation of the SMAD pathway via pSMAD2/3 is triggered by smoking and active in patients with mild to moderate COPD. These changes correlated to decline in lung function. Activation of the SMADs in the small airways is independent of TGF-ß1, suggesting factors other than TGF-ß1 are driving these pathways. These factors may have implications for small airway pathology in smokers and COPD through the process of EMT, however more mechanistic work is needed to prove these correlations.
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Obstrução das Vias Respiratórias , Doença Pulmonar Obstrutiva Crônica , Proteínas Smad , Fator de Crescimento Transformador beta1 , Humanos , Transição Epitelial-Mesenquimal , Transdução de Sinais , FumantesRESUMO
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
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Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Animais , Camundongos , Neutrófilos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pulmão , InflamaçãoRESUMO
Background: We have previously reported arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and suggested that endothelial-to-mesenchymal transition (EndMT) might be central to these changes. This study aims to provide evidence for active EndMT in IPF patients. Methods: Lung resections from 13 patients with IPF and 15 normal controls (NCs) were immunostained for EndMT biomarkers: vascular endothelial cadherin (VE-cadherin), neural cadherin (N-cadherin), S100A4 and vimentin. Pulmonary arteries were analysed for EndMT markers by using computer- and microscope-assisted image analysis software Image ProPlus7.0. All the analysis was done with observer blinded to subject and diagnosis. Results: Increased expression of mesenchymal markers N-cadherin (p<0.0001), vimentin (p<0.0001) and S100A4 (p<0.05) was noted with downregulation of junctional endothelial VE-cadherin (p<0.01) in the intimal layer of the arteries from patients with IPF compared to NCs. Cadherin switch was observed in IPF patients, showing increase in endothelial N-cadherin and decrease in VE-cadherin (p<0.01). There was also VE-cadherin shift from junctions to cytoplasm (p<0.01), effecting endothelial cell integrity in patients with IPF. In IPF, individual mesenchymal markers vimentin and N-cadherin negatively correlated with diffusing capacity of the lungs for carbon monoxide (r'=â -0.63, p=0.03 and r'=â -0.66, p=0.01). Further, N-cadherin positively correlated with arterial thickness (r'=0.58, p=0.03). Conclusion: This is the first study to demonstrate active EndMT in size-based classified pulmonary arteries from IPF patients and potential role in driving remodelling changes. The mesenchymal markers had a negative impact on the diffusing capacity of the lungs for carbon monoxide. This work also informs early origins of pulmonary hypertension in patients with IPF.
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Glioblastoma (GBM) is presented with a poor prognosis. The endoplasmic reticulum stress (ERS) has been implicated as a major contributor to disease progression and chemoresistance in GBM. Triggering ERS by chemical agents or genetic modulations is identified as some of the reasons for regulating gene expression and the pathogenesis of GBM. ERS initiates unfolded protein response (UPR), an integrated system useful in restoring homeostasis or inducing apoptosis. Modulation of UPR might have positive outcomes in GBM treatment as UPR inducers have been shown to alter cell survival and migration. In the current review, we have utilized GSE7806, a publicly available dataset from Gene Expression Omnibus (GEO), to evaluate the genes expressed during 6.5 hr and 18 hr, which can be comparable to the early and late-onset of the disease. Subsequently, we have elucidated the prognosis and survival information whilst the expression of these genes in the GBM was noted in previous studies. This is the first of its kind review summarizing the most recent gene information correlating UPR and GBM.
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Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático , ApoptoseRESUMO
BACKGROUND: Ovarian cancer remains a leading cause of mortality in women. It is known that long non-coding RNA (lncRNA) controls various biological processes and pathogenesis of many diseases, including cancers. This study aimed to determine whether LINC00936 and microRNA-221-3p (miR-221-3p) influence the laminin alpha 3 chain gene (LAMA3) in the development of ovarian cancer. METHODS: The expressions of LINC00936, miR-221-3p, and LAMA3 in ovarian cancer and adjacent tissues were assessed. Furthermore, ovarian cancer cells were transfected with vectors with overexpressed LINC00936, miR-221-3p mimic, miR-221-3p inhibitor, and si-LAMA3 to elucidate their functions in ovarian cancer cell proliferation, migration, invasion, angiogenesis, and tumorigenesis. The binding relationship between LINC00936 and miR-221-3p and the relationship between miR-221-3p and LAMA3 were verified to explore the mechanism of action of LINC00936 in ovarian cancer. LINC00936 binds to miR-221-3p as a ceRNA and regulates the expression of LAMA3. RESULTS: LINC00936 and LAMA3 were poorly expressed, while miR-221-3p was highly expressed in ovarian cancer tissues. Over-expression of LINC00936 contributed to decreasing miR- 221-3p expression and increasing LAMA3 expression. LINC00936 overexpression or miR-221- 3p silencing downregulated the levels of PCNA, MMP-2, MMP-9, and VEGF and decreased cell proliferation, migration, invasion, angiogenesis, and ovarian cancer tumorigenesis. CONCLUSION: Collectively, overexpression of LINC00936 suppressed the development of ovarian cancer by competitively binding to miR-221-3p and controlling LAMA3 expression. These results could serve as a novel theoretical base for the treatment of ovarian cancer.
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MicroRNAs , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/genética , MicroRNAs/genéticaRESUMO
Oral microbial ecosystems are vital in maintaining the health of the oral cavity and the entire body. Oral microbiota is associated with the progression of oral diseases such as dental caries, periodontal diseases, head and neck cancer, and several systemic diseases such as cardiovascular disease, rheumatoid arthritis, adverse pregnancy outcomes, diabetes, lung infection, colorectal cancer, and pancreatic cancer. Buccal mucosa, tongue dorsum, hard palate, saliva, palatine tonsils, throat, keratinized gingiva, supra-gingival plaque, subgingival plaque, dentures, and lips are microbial habitats of the oral cavity. Porphyromonas gingivalis may have a role in the development of periodontal diseases, oral cancer, diabetes, and atherosclerotic disease. Fusobacterium nucleatum showed a higher abundance in periodontal diseases, oral and colon cancer, adverse pregnancy outcomes, diabetes, and rheumatoid arthritis. The higher abundance of Prevotella intermedia is typical in periodontal diseases, rheumatoid arthritis, and adverse pregnancy outcome. S. salivarius displayed higher abundance in both dental caries and OSCC. Oral bacteria may influence systemic diseases through inflammation by releasing pro inflammatory cytokines. Identification of oral bacteria using culture-dependent approaches and next-generation sequencing-based metagenomic approaches is believed to significantly identify the therapeutic targets and non-invasive diagnostic indicators in different human diseases. Oral bacteria in saliva could be exploited as a non-invasive diagnostic indicator for the early detection of oral and systemic disorders. Other therapeutic approaches such as the use of probiotics, green tea polyphenol, cold atmospheric plasma (CAP) therapy, antimicrobial photodynamic therapy, and antimicrobial peptides are used to inhibit the growth of biofilm formation by oral bacteria.
Porphyromonas gingivalis may have a role in the development of periodontal diseases, oral cancer, diabetes, and atherosclerotic diseaseFusobacterium nucleatum showed a higher abundance in periodontal diseases, oral and colon cancer, adverse pregnancy outcomes, diabetes, and rheumatoid arthritisOral bacteria may influence systemic diseases through inflammation by releasing pro inflammatory cytokines.Identification of oral bacteria in saliva may be used as a non-invasive diagnostic indicator for the early detection of oral and systemic disorders.
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Artrite Reumatoide , Cárie Dentária , Microbiota , Doenças Periodontais , Feminino , Humanos , Gravidez , Doenças Periodontais/microbiologia , Porphyromonas gingivalisRESUMO
It is desired and urgently needed to improve the sensitivity of immunochromatography assay (ICA) for hazardous chemicals. In this work, an enhanced ICA strip was established and evaluated for simultaneous, semi-quantitative and quantitative detection of ochratoxin A (OTA) and aflatoxin B1 (AFB1). The signal strategy based on gold growth on the surface of the E. coli K12 carrier was recommended, which was successfully self-assembled on the enhanced ICA with a double test line pattern. When used as a novel carrier, the E. coli K12 could provide a larger surface area, better biocompatibility and high loading capacity, which was of great help to improve the performance of the ICA. By the naked eye, the semi-quantitative limit of detection (semi-Q-LOD) reached 0.03 ng/mL for both OTA and AFB1 (17-fold and 33-fold lower than the conventional ICA strip). By the digitized strip reader, the quantitative LODs (Q-LODs) were all identified as 0.01 ng/mL for two mycotoxins (10-fold improvement), with detection ranges of 0.01-0.5 ng/mL for OTA and 0.01-0.2 ng/mL for AFB1. Furthermore, the high reliability and applicability of the ICA were confirmed by its good correlation with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The advantages of the improved sensitivity, high efficiency and cost savings had been reflected for the ICA. This study could provide an important reference method for the sensitive, simultaneous, rapid and on-site monitoring of multicomponent contaminants.
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Micotoxinas , Aflatoxina B1/análise , Cromatografia de Afinidade/métodos , Cromatografia Líquida , Escherichia coli , Ouro/química , Substâncias Perigosas/análise , Limite de Detecção , Micotoxinas/análise , Reprodutibilidade dos Testes , Espectrometria de Massas em TandemRESUMO
Introduction: Pulmonary vascular remodelling in chronic obstructive pulmonary disease (COPD) has detrimental consequences for lung physiology. The aim of our study was to provide a comprehensive size-based morphometric quantification of pulmonary arterial remodelling in smokers and in patients with small airway disease (SAD) or COPD. Method: Movat's pentachrome staining was performed on lung resections for 46 subjects: 12 never-smoker normal controls (NC), six normal lung function smokers (NLFS), nine patients with SAD, nine patients with mild-to-moderate COPD who were current smokers (COPD-CS) and 10 patients with mild-to-moderate COPD who were ex-smokers (COPD-ES). Following a size-based classification of pulmonary arteries, image analysis software was used to measure their number, total wall thickness, individual layer thickness and elastin percentage. Results: All pathological groups showed decreased numbers of pulmonary arteries compared with the NC group in all artery sizes. Arterial wall thickness was greater in NLFS and COPD-CS than in NC. Thickness in COPD-ES was decreased compared with COPD-CS. Intimal thickness was greater in all pathological groups in all arterial sizes than in the NC group. Medial thickness was also greater in small and medium arteries. Intimal thickness of larger arteries in COPD-CS correlated negatively to forced expiratory volume in 1â s/forced vital capacity (FVC) % and forced expiratory flow at 25-75% of FVC. Elastin deposition in small arteries was greatest in COPD-CS. Intimal elastin deposition had a more negative correlation with intimal thickness in NLFS and SAD than in COPD-CS. Conclusion: Smoking, SAD and mild-to-moderate COPD are associated with pruning and a decrease in the number of pulmonary arteries, increased wall thickness and variable elastin deposition. These changes were associated with worse airway obstruction.
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Management of patients with asthma COPD overlap (ACO) is clinically challenging due to insufficient evidence of pathological changes in these patients. In this cross-sectional study, we evaluated airway remodeling in endobronchial biopsies from a total of 90 subjects, which included 12 ACO, 14 patients with asthma, 12 COPD exsmokers (ES), 11 current smokers (CS), 28 healthy controls (HC), and 13 normal lung function smokers (NLFS). Tissue was stained with Masson's trichrome. Epithelium, goblet cells, reticular basement membrane (RBM), cellularity, lamina propria (LP), and smooth muscle (SM) changes were measured using Image-Pro Plus v7 software. Differential airway remodeling pattern was seen in patients with ACO. A limited change was noted in the ACO epithelium compared with other pathological groups. RBM was substantially thicker in patients with ACO than in HC (P < 0.0002) and tended to be thicker than in patients with asthma and NLFS. The total RBM cells were higher in ACO than in the HC (P < 0.0001), COPD-CS (P = 0.0559), -ES (P = 0.0345), and NLFS (P < 0.0002), but did not differ from patients with asthma. Goblet cells were higher in the ACO than in the HC (P = 0.0028) and COPD-ES (P = 0.0081). The total LP cells in ACO appeared to be higher than in HC, COPD-CS, and NLFS but appeared to be lower than in patients with asthma. Finally, SM area was significantly lower in the ACO than in patients with asthma (P = 0.001), COPD-CS (=0.0290), and NLFS (P = 0.0011). This first comprehensive study suggests that patients with ACO had distinguishable tissue remodeling that appeared to be more severe than patients with asthma and COPD. This study will help in informed decision-making for better patient management in clinical practice.