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Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the association between sex hormones and the risk of pulmonary fibrosis by conducting a meta-analysis of previously published studies. Methods: We executed a comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases to locate pertinent studies published up to April 2024. We included studies that reported the association between sex hormones and the risk of pulmonary fibrosis. Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results: A total of 10 articles, encompassing 1371 patients, were finally incorporated in this meta-analysis. Based on the evaluation of the included studies, it was observed that the levels of dehydroepiandrosterone sulfate (DHEA-S) (pooled SMD: −0.72, 95% CI: −1.21 to −0.24, p < 0.001), testosterone (pooled SMD: −1.25, CI: −2.39 and −0.11, p < 0.001) and estrogen (pooled SMD: −0.56, 95% CI: −0.96 to −0.15, p < 0.001) were significantly lower in patients with pulmonary fibrosis, whereas the levels of luteinizing hormone (LH) remained unaffected. Publication bias was ruled out through funnel plots. Conclusion: This meta-analysis indicates that reduced levels of DHEA-S, testosterone, estrogen may serve as potential risk factors for pulmonary fibrosis. There is a pressing need for additional studies to confirm this association and explore the underlying biological mechanisms. Clinicians should recognize the potential influence of sex hormones in the etiology of pulmonary fibrosis and consider this aspect during the patient management process. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies. There is a growing body of evidence showing that long non‐coding RNAs (lncRNAs) play critical roles in ESCC oncogenesis. The present study aimed to explore the role of LOC101928477, a newly discovered lncRNA, in the development and metastasis of ESCC. Methods: In this study, real‐time PCR, western blotting, cell counting kit‐8 (CCK‐8), flow cytometry, colony formation, wound healing, transwell migration/invasion assay, immunofluorescence, and immunohistochemistry were used. We also applied an in situ xenograft mouse model and a lung metastasis mouse model to verify our findings. Results: We determined that LOC101928477 expression was inhibited in ESCC tissue and ESCC cell lines when compared with controls. Moreover, forced expression of LOC101928477 effectively inhibited ESCC cell proliferation, colony formation, migration, and invasion via suppression of epithelial‐mesenchymal transition (EMT). Furthermore, LOC101928477 overexpression inhibited in situ tumor growth and lung metastasis in a mouse model. Conclusions: Together, our results suggested that LOC101928477 could be a novel suppressor gene involved in ESCC progression. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed.Methods: We used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin.Results: The present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage.Conclusions: The current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments.Methods: Mcl-1 expression was measured by reverse transcription (RT)-PCR and Western blotting. Human Mcl-1 promoter activity was evaluated by reporter gene assay. The interactions between DNA and transcription factors were confirmed by electrophoretic mobility shift assay (EMSA) in vitro and by chromatin immunoprecipitation (ChIP) assay in cells.Results: Four human ESCC cell lines, TE-1, Eca109, KYSE150 and KYSE510, are revealed increased levels of Mcl-1 mRNA and protein compare with HaCaT, an immortal non-tumorigenic cell line. Results of reporter gene assays demonstrate that human Mcl-1 promoter activity is decreased by mutation of kappaB binding site, specific NF-kappaB inhibitor Bay11-7082 or dominant inhibitory molecule DNMIkappaBalpha in TE-1 and KYSE150 cell lines. Mcl-1 protein level is also attenuated by Bay11-7082 treatment or co-transfection of DNMIkappaBalpha in TE-1 and KYSE150 cells. EMSA results indicate that NF-kappaB subunits p50 and p65 bind to human Mcl-1-kappaB probe in vitro. ChIP assay further confirm p50 and p65 directly bind to human Mcl-1 promoter in intact cells, by which regulates Mcl-1 expression and contributes to the viability of TE-1 cells.Conclusions: Our data provided evidence that one of the mechanisms of Mcl-1 expression in human ESCC is regulated by the activation of NF-kappaB signaling. The newly identified mechanism might provide a scientific basis for developing effective approaches to treatment human ESCC. [ABSTRACT FROM AUTHOR]

Airway remodeling is a critical factor determining the pathogenesis and treatment sensitivity of severe asthma (SA) or uncontrolled asthma (UA). The activation of epithelial-mesenchymal trophic units (EMTUs) regulated by airway epithelial cells (AECs) has been proven to induce airway remodeling directly. However, the triggers for EMTU activation and the underlying mechanism of airway remodeling are not fully elucidated. Here, we screened the differentially expressed gene Cathepsin C (CTSC)/dipeptidyl peptidase 1 (DPP-1) in epithelia of SA and UA patients using RNA sequencing data and further verified the increased expression of CTSC in induced sputum of asthma patients which was positively correlated with the severity and airway remodeling. Moreover, direct instillation of exogenous CTSC induced airway remodeling. Genetic inhibition of CTSC suppressed EMTU activation and airway remodeling in two asthma models with airway remodeling. Mechanistically, increased secretion of CTSC from AECs induced EMTU activation through p38-mediated pathway, further inducing airway remodeling. Meanwhile, inhibition of CTSC also reduced the infiltration of inflammatory cells and the production of inflammatory factors in the lungs of asthmatic mice. Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA.

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.

Objective: To analyze the components of tumor infiltrating T lymphocyte (TIL) cells in malignant pleural effusion of lung adenocarcinoma, and evaluate their killing activities to autologous tumor cells. 
 Methods: Malignant pleural effusions were collected from 17 patients with lung adenocarcinoma. Mononuclear cells were isolated by Ficoll density gradient centrifugation and flow cytometer was used to analyze TIL cell components. TIL and tumor cells were separated through adherent culture. The tumor cells were identified via intramuscular injection of adherent cells into nude mice and the killing effect of cultured lymphocytes on autologous tumor cells was studied.
 Results: Of the TIL in malignant pleural effusions, T cells accounted for 60.6%-79.3%, while T helper cells were significantly higher than T killer cells (36.63%±1.90% vs 24.64%±2.32%, P<0.001). There were also natural killer (NK) cells and NK T cells in the effusions. Tumor cells were successfully isolated and cultured. The killing activity of cultured TIL to autologous tumor cells was 39.14%±12.04%, and the killing activity of TIL with high proliferation rate to autologous tumor cells was higher than that of low proliferation group (50.51%±3.80% vs 29.04%±5.77%, P<0.001).
 Conclusion: T lymphocytes are the major components of TIL in malignant pleural effusions derived from lung adenocarcinoma, and T helper cells are more than T killer cells. The killing activity of TIL with strong proliferation ability to autologous tumor cells is higher than that of TIL with weak proliferation ability. Therefore, cells from malignant pleural effusions could be used for cellular immunotherapy against tumor.

LIM and SH3 protein 1 (LASP1) is an actin-binding protein which is overexpressed in many types of cancers and plays important roles in cancer progression. however, the role of LASP1 in esophageal squamous cell carcinoma (ESCC) is still unknown. We sought to analyze the expression level of LASP1 in ESCC, and the role of LASP1 in the development of ESCC was further investigated. We evaluated the expression levels of LASP1 in 89 ESCC tissues and two ESCC cell lines using quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. The effects of LASP1 depletion on tumor cell behavior were investigated using gene transfection and small interfering RNA (siRNA) in ESCC cell lines in vitro. The expression levels of LASP1 at the mRNA and protein levels were significantly higher in ESCC tissues and ESCC cell lines compared to adjacent tissues. Immunohistochemistry showed that LASP1 was localized in the cytoplasm and nuclei of tumor epithelia. Silencing of LASP1 in ECA109 and KYSE510 cell lines significantly inhibited cell proliferation, migration and invasion when compared with the negative control cells in vitro. LASP1 may play an important role in the pathogenesis of ESCC and shows promise as a treatment target in ESCC.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide. EC is usually diagnosed at a locally advanced stage or at a stage with involvement of lymph nodes. Despite aggressive treatment, the overall five-year survival rate remains poor. microRNAs (miRNAs) are small, non-coding endogenous RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level. Accumulating evidence suggests that the deregulation of miRNAs not only results in cancer progression, but also directly promotes tumor initiation. Previous studies found that miRNAs are frequently deregulated in EC, indicating that miRNAs are important in tumorigenesis. In this review, we summarize therecently recognized miRNA expression and its impact on the biology of EC and the potential applications for EC.