Role Of Lung Research Articles

Is there a role for lung or bronchial biopsies for the diagnosis of mycobacterial pulmonary disease in patients with bronchiectasis?

BackgroundWorkup of bronchiectasis patients mandates microbiological characterization often being sought via Bronchoscopy. However, whether to perform bronchial or lung biopsies, is unknown, especially for the diagnosis of NTM pulmonary disease. We aimed to assess the current practice and yield of the different bronchoscopic procedures in this setting. MethodsData from an adult cohort with bronchiectasis referred for bronchoscopy for microbiologic sampling was reviewed, including demographics, etiology, imaging and results of the different bronchoscopic procedures performed. Results127 subjects were analyzed (mean age 61, 56% female). BAL culture was positive in 44%. Frequent pathogens were Hemophilus Influenza (20%), pseudomonas aeruginosa (8%) and Staphylococcus aureus (7%). NTM and tuberculosis were found in 6% and 1.5% respectively. BAL cytology was sent in 125 procedures, EBB was performed in 51 patients (40%) and TBLB in 38 patients (30%). BAL cytology and both EBB and TBB (including tissue cultures) had no benefit over BAL with respect to microbiological diagnosis, including identification of mycobacterial disease. ConclusionsIn adult subjects with Non-CF bronchiectasis requiring bronchoscopy for microbiological characterization, BAL cytology and lung tissue biopsies were frequently performed but were of minimal additional benefit over BAL culture (including for mycobacterial pulmonary disease), and are most likely futile.

Loss of Blood Group Antigens in Haematolymphoid Malignancy: A Case Series from a Cancer Institute from North East India

Introduction: Altered expression of blood group antigens has been reported to be associated with both solid as well as haematological malignancies. This usually results from genetic mutation leading to incomplete as well as abnormal synthesis of antigens. Transitional loss of RBC antigens especially from ABO system is most commonly found in haematological malignancies causing blood group discrepancies and followed by reversal to its historical blood group during remission. Loss of A, B antigens has also been associated to play a role in lung, bladder and colon cancers. However not much data is available regarding haematological malignancies.Methods and Methodology: Retrospective review of blood group discrepancy (Forward group) in patients admitted for haematolymphoid malignancy at our institute was done during a period of 3.5 years (13/3/2020 till 12/9/2023). Blood grouping done by Column agglutination test were repeated by conventional tube method. Further confirmation of the group was done by saliva test and adsorption elution test as indicated. The detail history of the patient was collected from the hospital records and analysed. Results: A total of 7 patients presented with either loss or decrease in antigen expression. Most common diagnosis was Acute Myeloid Leukaemia (AML) with FLT3 mutation and most common antigen affected was A. Conclusion: Haematolymphoid malignancies has been associated with loss of blood group antigens causing group discrepancy. Blood transfusion is an integral part of the supportive care in these patients. Hence, proper work up of blood group discrepancy cases should be done and recorded so as to prevent delay in blood transfusion.

Exploration of oxidized phosphocholine profile in non-small-cell lung cancer.

Introduction: Lung cancer is one of the most frequently studied types of cancer and represents the most common and lethal neoplasm. Our previous research on non-small cell lung cancer (NSCLC) has revealed deep lipid profile reprogramming and redox status disruption in cancer patients. Lung cell membranes are rich in phospholipids that are susceptible to oxidation, leading to the formation of bioactive oxidized phosphatidylcholines (oxPCs). Persistent and elevated levels of oxPCs have been shown to induce chronic inflammation, leading to detrimental effects. However, recent reports suggest that certain oxPCs possess anti-inflammatory, pro-survival, and endothelial barrier-protective properties. Thus, we aimed to measure the levels of oxPCs in NSCLC patients and investigate their potential role in lung cancer. Methods: To explore the oxPCs profiles in lung cancer, we performed in-depth, multi-level metabolomic analyses of nearly 350 plasma and lung tissue samples from 200 patients with NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), the two most prevalent NSCLC subtypes and COPD patients as a control group. First, we performed oxPC profiling of plasma samples. Second, we analyzed tumor and non-cancerous lung tissues collected during the surgical removal of NSCLC tumors. Because of tumor tissue heterogeneity, subsequent analyses covered the surrounding healthy tissue and peripheral and central tumors. To assess whether the observed phenotypic changes in the patients were associated with measured oxPC levels, metabolomics data were augmented with data from medical records. Results: We observed a predominance of long-chain oxPCs in plasma samples and of short-chain oxPCs in tissue samples from patients with NSCLC. The highest concentration of oxPCs was observed in the central tumor region. ADC patients showed higher levels of oxPCs compared to the control group, than patients with SCC. Conclusion: The detrimental effects associated with the accumulation of short-chain oxPCs suggest that these molecules may have greater therapeutic utility than diagnostic value, especially given that elevated oxPC levels are a hallmark of multiple types of cancer.

GREB1L overexpression is associated with good clinical outcomes in breast cancer

BackgroundBreast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer.MethodsThe Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells.ResultsGREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis.ConclusionThese results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

Irrealis Mood in Lung’Ie: Ka

This paper describes and analyzes the ka particle in constructions with dynamic predicates in Lung’Ie, an endangered Portuguese-lexifier creole language spoken on Príncipe Island. In contrast with the literature on Lung’Ie (GÜNTHER, 1973; MAURER, 2009), we argue that ka plays one single role in Lung’Ie: marking the irrealis mood (cf. AGOSTINHO; RECH, 2022). Our data shows that ka is found in hypothetical, conditional, and counterfactual constructions, as well as in future and habitual aspect constructions. We also verified that ka is not used in past constructions nor in those that describe events at the time of the speech – prototypical realis contexts.

The Clinical and Biological Effects of Receptor Expression-Enhancing Protein 6 in Tongue Squamous Cell Carcinoma.

There are currently no effective biomarkers for the diagnosis and treatment of tongue squamous cell carcinoma (TSCC), which causes a poor 5-year overall survival rate. Thus, it is crucial to identify more effective diagnostic/prognostic biomarkers and therapeutic targets for TSCC patients. The receptor expression-enhancing protein 6 (REEP6), a transmembrane endoplasmic reticulum resident protein, controls the expression or transport of a subset of proteins or receptors. Although it was reported that REEP6 plays a role in lung and colon cancers, its clinical impact and biological role in TSCC are still unknown. The present study aimed to identify a novel effective biomarker and therapeutic target for TSCC patients. Expression levels of REEP6 in specimens from TSCC patients were determined with immunohistochemistry. Gene knockdown was used to evaluate the effects of REEP6 in cancer malignancy (colony/tumorsphere formation, cell cycle regulation, migration, drug resistance and cancer stemness) of TSCC cells. The clinical impact of REEP6 expression and gene co-expression on prognosis were analyzed in oral cancer patients including TSCC patients from The Cancer Genome Atlas database. Tumor tissues had higher levels of REEP6 compared to normal tissues in TSCC patients. Higher REEP6 expression was related to shorter disease-free survival (DFS) in oral cancer patients with poorly differentiated tumor cells. REEP6-knocked-down TSCC cells showed diminished colony/tumorsphere formation, and they also caused G1 arrest and decreased migration, drug resistance and cancer stemness. A high co-expression of REEP6/epithelial-mesenchymal transition or cancer stemness markers also resulted in poor DFS in oral cancer patients. Thus, REEP6 is involved in the malignancy of TSCC and might serve as a potential diagnostic/prognostic biomarker and therapeutic target for TSCC patients.

Pancancer Analysis of the Prognostic and Immunotherapeutic Value of Progestin and AdipoQ Receptor 4.

AdipoQ receptor 4 (PAQR4) belongs to the family of progestin and AdipoQ receptors. PAQR4 plays an oncogenic role in lung and breast cancer. However, systematic pancancer analyses of PAQR4 have not been performed. The purpose was to investigate the prognostic and immunological significance of PAQR4 across 31 tumor types. Data were obtained from the following sources: TCGA, GEO, UALCAN, TIMER, GEPIA2, KM plotter, and TISIDB databases. The results proved that PAQR4 expression was significantly elevatory in most cancer types. We then explored the utility of PAQR4 as a prognostic indicator across all cancers. Using Cox proportional risk regression models, it has been demonstrated that PAQR4 is an independent risk factor in. High PAQR4 expression was not associated with other prognostic indicators, including overall survival, disease-free interval, disease-specific survival, and progression-free period. Subsequently, we explored the immunological value of PAQR4 and found that PAQR4 expression significantly correlated with tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoint genes in tumors. It also significantly negatively correlated with most tumors' ESTIMATE scores, indicating that PAQR4 can influence the cellular composition of the tumor microenvironment. Our findings suggest the immunotherapeutic potential of PAQR4 in tumors. Finally, we explored the role of PAQR4 in tumor drug resistance and found that PAQR4 expression affected the sensitivity to multiple chemotherapeutic agents. A significant role for PAQR4 in tumor immunity is evident in these studies, as well as its potential role in cancer diagnosis, prognosis, and treatment precision.

LncRNA DDX11-AS1 Promotes Chemoresistance through LIN28A-Mediated ATG12 mRNA Stabilization in Breast Cancer

Introduction: During breast cancer chemotherapy, the chemoresistance that frequently accompanies the treatment has become a big challenge. Long noncoding RNAs (LncRNAs) have been related to the development of chemoresistance in multiple cancer types. LncRNA DDX11-AS1 has shown a carcinogenic role in lung and colorectal cancer and was reported to enhance oxaliplatin resistance in gastric cancer and Taxol insensitivity in esophageal cancer. But its role in breast cancer chemotherapy drug resistance remains unknown. This study aimed to investigate the function and mechanism of lncRNA DDX11-AS1 in breast cancer chemoresistance. Methods: The relationship between DDX11-AS1 and adriamycin (ADR) resistance was confirmed by qPCR, cell viability tests, and survival analysis. Then, RNA immunoprecipitation was conducted to evaluate the interaction between DDX11-AS1 and RNA-binding protein LIN28A. The regulation effect of LIN28A on autophagy-related genes ATG7 or ATG12 was detected by RNA stability assay and Western blot. Their correlation analysis was evaluated in GEO datasets and further validated by immunohistochemical results. The clinical significance of DDX11-AS1, ATG7, or ATG12 was evaluated by Kaplan-Meier Plotter analysis. Results: Here, we reported DDX11-AS1 was significantly upregulated in chemoresistant breast cancer cells and overexpression of DDX11-AS1 promoted ADR resistance in breast cancer. LIN28A could interact with DDX11-AS1 and was involved in DDX11-AS1-mediated ADR resistance. Interfering with LIN28A reversed DDX11-AS1-induced ADR resistance. LIN28A could increase the protein level of ATG7 and ATG12 by increasing their mRNA stability. Survival analysis showed that ATG12 expression level was negatively correlated with the prognosis of breast cancer patients. Conclusion: This study clarifies the role of DDX11-AS1 in breast cancer chemoresistance and revealed a new mechanism, that is, interacting with LIN28A to stabilize ATG7 and ATG12 and jointly promote chemorefractory. These findings warrant further in vivo investigations to study DDX11-AS1 as a potential target to overcome chemoresistance.

Machine learning identifies characteristics molecules of cancer associated fibroblasts significantly correlated with the prognosis, immunotherapy response and immune microenvironment in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a highly lethal disease with a dramatic pro-fibrocytic response. Cancer-associated fibroblasts (CAFs) have been reported to play a key role in lung adenocarcinoma. Marker genes of CAFs were obtained from the Cell Marker website. Single sample gene set enrichment analysis (ssGSEA) was used for CAFs quantification. R and GraphPad Prism software were utilized for all analysis. Quantitative real-time PCR (qRT-PCR) was utilized to detect the RNA level of specific molecules. Based on the ssGSEA algorithm and obtained CAFs markers, the LUAD patients with low- and high-CAFs infiltration were successfully identified, which had different response patterns to immunotherapy. Through the machine learning algorithm - LASSO logistic regression, we identified 44 characteristic molecules of CAFs. Furthermore, a prognosis signature consisting of seven characteristic genes was established, which showed great prognosis prediction ability. Additionally, we found that patients in the low-risk group might have better outcomes when receiving immunotherapy of PD-1, but not CTLA4. Also, the biological enrichment analysis revealed that immune response-related pathways were significantly associated with CAFs infiltration. Meanwhile, we investigated the underlying biological and microenvironment difference in patients with high- and low-risk groups. Finally, we identified that AMPD1 might be a novel target for LUAD immunotherapy. Patients with a high level of AMPD1 were correlated with worse responses to immunotherapy. Moreover, immunohistochemistry showed that the protein level of AMPD1 was higher in lung cancer. Results of qRT-PCR demonstrated that AMPD1 was upregulated in A549 cells compared with BEAS-2B. Meanwhile, we found that the knockdown of AMPD4 can significantly reduce the expression of CTLA4 and PDCD1, but not CD274 and PDCD1LG2. We comprehensively explored the role of CAFs and its characteristics molecules in LUAD immunotherapy and developed an effective signature to indicate patients prognosis and immunotherapy response. Moreover, AMPD1 was identified as a novel target for lung cancer immunotherapy.

Therapeutic potential of autophagy activators and inhibitors in lung and breast cancer- a review.

Autophagy is a cellular process that eliminates damaged components of cytoplasm via the lysosome. Autophagy supports cells and tissues to remain healthy by recycling old or damaged cellular organelles and proteins with new ones. The breakdown products that follow are directed into cellular metabolism, where they are utilized to produce energy as well as for maintaining homeostasis and stability of the genome. In many cancers, autophagy modulation carries out a dual role in cancer development and suppression. Autophagy suppresses the proliferation of cancer cells by bringing about cell death and limiting cancer cell development, although it also promotes tumorigenesis by encouraging cancer cell growth and formation. Nevertheless, autophagy's implication in cancer remains a paradox. While several autophagy activators, and inhibitors, such as SAH-EJ2, Gefitinib, Ampelopsin hydroxychloroquine and chloroquine, are utilized to regulate autophagy in chemoprevention, the exact intrinsic system of autophagy in cancer deserves further investigation. Despite improved treatment regimens, the incidence rate of both breast and lung cancer has grown, as has the number of recurrence cases. Hence, this review offers a wide overview of autophagy's underlying role in lung and breast cancer, particularly focusing on the various autophagy activators and inhibitors in both cancers, as well as the use of various organic compounds, regular drugs, and natural products in cancer prevention and treatment.

MFAP2 contributes to the proliferation and motility of lung cancer cells via Wnt/β-catenin pathway

Purpose: To measure microfibrillar-associated protein 2 (MFAP2) expression levels in lung cancer and identify its role in lung cancer.Methods: Immunoblots and PCR were used to determine the expression of MFAP2 in lung cancer cell lines. The effects of MFAP2 on the viability and apoptosis of lung cancer cells were evaluated by CCK-8, colony formation, and flow cytometry (FCM) assays, while wound healing and Transwell assays were used to assess the effects of MFAP2 on the motility and epithelial-mesenchymal transition (EMT) of lung cancer cells. Immunoblot assays were also performed to determine the effect of MFAP2 on the Wnt/β-catenin axis in lung cancer cells.Results: MFAP2 was highly expressed in lung cancer cells. Depletion of MFAP2 suppressed the viability and stimulated apoptosis in these cells (p < 0.01). In addition, knockdown of MFAP2 suppressed the motility and EMT of lung cancer cells (p < 0.01). MFAP2 mediated the Wnt/β-catenin axis and affected the viability and motility of lung cancer cells.Conclusion: MFAP2 is a promising target for lung cancer treatment.

Interactions between EGFR and EphA2 promote tumorigenesis through the action of Ephexin1

The cell signaling factors EGFR, EphA2, and Ephexin1 are associated with lung and colorectal cancer and play an important role in tumorigenesis. Although the respective functional roles of EGFR and EphA2 are well known, interactions between these proteins and a functional role for the complex is not understood. Here, we showed that Ephexin1, EphA2, and EGFR are each expressed at higher levels in lung and colorectal cancer patient tissues, and binding of EGFR to EphA2 was associated with both increased tumor grade and metastatic cases in both cancer types. Treatment with Epidermal Growth Factor (EGF) induced binding of the RR domain of EGFR to the kinase domain of EphA2, and this binding was promoted by Ephexin1. Additionally, the AKT-mediated phosphorylation of EphA2 (at Ser897) promoted interactions with EGFR, pointing to the importance of this pathway. Two mutations in EGFR, L858R and T790M, that are frequently observed in lung cancer patients, promoted binding to EphA2, and this binding was dependent on Ephexin1. Our results indicate that the formation of a complex between EGFR, EphA2, and Ephexin1 plays an important role in lung and colorectal cancers, and that inhibition of this complex may be an effective target for cancer therapy.

Real-world clinical outcomes and molecular features of lung-specific and liver-specific metastases in pancreatic ductal adenocarcinoma (PDAC).

532 Background: PDAC remains one of the most lethal malignancies following metastatic presentation, typically to the liver or lung. Previous studies have observed that advanced PDAC patients have variable outcomes depending on site of involvement. Here, we aim to understand survival outcomes and molecular features for PDAC based on involvement of lung vs liver. Methods: We retrospectively analyzed longitudinal clinical outcomes across 787 patients with PDAC with next generation sequencing (NGS) from Perthera’s Real-World Evidence database whose tumors first metastasized to either the lung or the liver. Median overall survival (mOS) was measured from either the date of initial diagnosis (resectable cases only, stage I-III) or advanced diagnosis (stage IV) until death. Differences in survival and frequencies of mutations were evaluated between patients with lung-specific and liver-specific metastases using Cox regression and Fisher's exact test, respectively. Results: Among resectable PDAC, mOS from initial diagnosis was significantly shorter in patients that developed liver only metastasis (Table, left) compared to those patients that developed lung only metastasis (p=2.4e-08, HR=3.04 [2.06-4.49]). In the advanced PDAC cohort, mOS from diagnosis of advanced disease was also significantly shorter (Table, right) in liver only versus lung only metastasis (p=0.0013, HR=1.62 [1.21-2.18]). Differences in treatment-specific outcomes were not significant supporting a potential prognostic role for lung only metastases. PDAC tumors presenting to the liver first were modestly enriched (unadjusted p<0.05) for TP53 mutations (81.4% in liver vs 69.2% in lung), MYC amplifications (8.6% vs 3.0%), and inactivating CDK2NA alterations (51.5% vs 39.1%) whereas lung-specific mutation frequencies were higher for STK11 mutations (2.4% in liver vs 7.5% in lung), CCND1 amplifications (0.5% vs 3.0%), GNAS alterations (2.0% vs 8.5%). No differences in KRAS mutations nor specific isoforms were noted between lung vs liver only metastasis. Conclusions: Lung only metastasis in both resectable and advanced PDAC confers a significant survival advantage compared to liver only metastasis. Deeper investigation into the molecular drivers of site-specific metastases is warranted.[Table: see text]

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed. In vivo and in vitro experiments were conducted to explore the effects and molecular basis of ENKUR and CB in HCC. ENKUR expression was correlated with HCC progression and patient prognosis. Furthermore, ENKUR could inhibit tumor proliferation, metastasis, and sorafenib resistance in HCC. Mechanistic studies showed that ENKUR or its Enkurin domain could bind to MYH9 and decrease its expression by binding to β-catenin and inhibiting its nuclear transfer, thus decreasing c-Jun level. Low expression of MYH9 suppressed recruitment of deubiquitination enzyme USP7, promoting degradation of the c-Myc. Therefore, cell cycle and EMT signals were suppressed. CB as a safe and effective anti-cancer compound up-regulates the expression of ENKUR via inhibiting PI3K/AKT/c-Jun-mediated transcription suppression. These findings show that ENKUR induced by CB antagonizes β-catenin/c-Jun/MYH9/USP7 pathway, thus increasing c-Myc ubiquitin degradation and finally suppressing cell cycle and EMT signals.

UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer

Background: Ultrasound-targeted microbubble destruction (UTMD) is a new type of gene delivery technology. MiR-21-5p was highly expressed in a variety of cancers. In this paper, miR-21-5p inhibitor was transfected into lung cancer cells by UTMD to observe its role in lung cancer.Methods: StarBase was used to analyze the miR-21-5p expression in lung cancer patients and its relationship with the prognosis of the patients. MiR-21-5p expression in lung cancer tissues or cell lines was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Effects of gradient concentration (0, 5, 10, 20, 30%) of SonoVue or gradient mechanical index (MI) (0, 0.5, 1, 1.5, 2 W/cm2) on the cell viability were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The targeting relationship between miR-21-5p and B-cell translocation gene 2 (BTG2) was predicted by TargetScan and confirmed by dual-luciferase reporter assay, while the expressions of the two genes were determined by qRT-PCR. Through liposome transfection or UTMD transfection, the effects of miR-21-5p/BTG2 on the biological behaviors of lung cancer cells, the size of xenograft tumors and the expressions of ki67 and miR-21-5p were measured by qRT-PCR, western blot, cell function experiments and immunohistochemistry, respectively.Results: MiR-21-5p expression was upregulated in lung cancer, which was associated with a poor prognosis. The optimal ultrasound conditions were 10% SonoVue concentration and 1 W/cm2. UTMD transfection exerted a stronger effect than liposome transfection. MiR-21-5p promoted cell viability, proliferation and migration yet suppressed apoptosis by targeting BTG2. MiR-21-5p inhibitor reduced the size and volume of xenograft tumor and the expressions of ki67 and miR-21-5p in xenograft tumor tissues. ConclusionUTMD-mediated miR-21-5p inhibitor can more effectively suppress the development of lung cancer.

Reduced receptor for advanced glycation end products is associated with \u03b1-SMA expression in patients with idiopathic pulmonary fibrosis and mice

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Despite alveolar epithelial cells is crucial role in lung, its contribution and the associated biomarker remain unknown in the pathogenesis of IPF. Recently, environmental factors including stone dust, silica and cigarette smoking were found as risk factors involved in IPF. Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface receptors. It has been shown that interaction between RAGE and its ligands on immune cells mediates cellular migration and regulation of pro-inflammation. RAGE is highly expressed in the lung, in particular, alveolar epithelial cells. Therefore, we determined whether RAGE expression is associated with fibrosis-associated genes in patients with IPF and mice.ResultsWhen bleomycin (BLM) was intratracheally administered to C57BL/6 mice for 1, 2 weeks, macrophage and neutrophils were significantly increased. The fibrotic nodule formed and accumulation of collagen was determined after BLM injection in H&E- and Masson’s trichrome staining. Levels of elastin, Col1a1 and fibronectin were increased in quantitative real-time PCR and protein levels of α-SMA was increased in western blot analysis. In the lung tissues of 1 mg/kg BLM-induced mice, RAGE expression was gradually decreased in 1- and 2 weeks in immunohistochemistry and western blot analysis, and 3 mg/kg of BLM-induced mice exhibited decreased RAGE levels while α-SMA expression was increased. We next determined RAGE expression in the lungs of IPF patients using immunohistochemistry. As a result, RAGE expression was decreased, while α-SMA expression was increased compared with non-IPF subjects.ConclusionsOur findings suggest that reduced RAGE was associated with increased fibrotic genes in BLM-induced mice and patients with IPF. Therefore, RAGE could be applied with a biomarker for prognosis and diagnosis in the pathogenesis of IPF.

Role of lungs in the hemostasis system (review of literature).

The lung tissue contains various hemostatic system elements, which can be released from the lungs, both under physiological and pathological conditions. The COVID-19 pandemic has led to an increase in the number of patients with acute respiratory distress syndrome (ARDS) in intensive care units worldwide. When the lungs are damaged, coagulation disorders are mediated by tissue factor (TF) - factor VIIa (F VIIa), and inhibition of this pathway completely eliminates intrapulmonary fibrin deposition. A tissue factor pathway inhibitor TFPI also contributes to pulmonary coagulationdisturbance in ARDS. Pulmonary coagulationdisturbance caused by pneumonia can worsen the damage to the lungs and thus contribute to the progression of the disease. Cytokines are the main linking factors between inflammation and changes in blood clotting and fibrinolysis. The sources of proinflammatory cytokines in the lungs are probably alveolar macrophages. The activation of alveolar macrophages occurs through the nuclear factor kappa-bi (NF-κB), which controls thetranscription of the expression of immune response genes, cell apoptosis, which leads to the development of inflammation and autoimmune diseases as a result of direct stimulation of TF activation. Conversely,coagulation itself can affect bronchoalveolar inflammation. Coagulation leads to the formation of proteases that interact with specific cellular receptors, activating intracellular signaling pathways. The use of anticoagulant therapy, which also has an anti-inflammatory effect, perhaps one of the therapeutic targets for coronavirus infection.The difficulty here is that it seems appropriate to study anticoagulant interventions' influence on clinically significant cardio-respiratory parameters.

Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3\u03b2 axis

BackgroundPropofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β).MethodsC57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured.ResultsOur experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression.ConclusionOverall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

Characterizing Canine Hepatobiliary Neuroendocrine Neoplasia: A Proteomic Approach

Hepatobiliary neuroendocrine neoplasia is an extremely rare cancer in humans and other species. In humans, neuroendocrine neoplasia of the liver and gallbladder represents less than 2% of all gastroenteropancreatic neuroendocrine neoplasia. In the veterinary literature, there is a paucity of information on hepatobiliary neuroendocrine cancer with only a small number of published studies. Improved characterization of these tumors is needed to identify additional biomarkers for diagnosis and generate informed treatment protocols for human and veterinary patients. Here, we applied a proteomics strategy to identify differentially expressed proteins in canine hepatobiliary neoplasia as compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Our objective was to identify unique protein biomarkers and possible chemotherapeutic targets. Thirty-four up-regulated, differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasia samples. Galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression, was among them. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.

The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung.

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.