[Research Progress on the Mechanism and Diagnostic Markers of Bone Metastasis 
in Small Cell Lung Cancer].

Small cell lung cancer (SCLC) is a type of lung cancer with high malignant degree, rapid transformation, rapid invasion and metastasis, which is prone to early metastasis and poor prognosis. Bone metastases of SCLC occur in three stages: cancer cells proliferate at the primary site, break through local tissues, enter the blood circulation to form circulating tumor cells (CTCs), reach bone tissue through blood circulation, and take root and germinate to form new tumor sites with the support of the bone microenvironment. However, traditional imaging and pathology examinations have disadvantages such as low sensitivity, high cost and difficulty in implementation. Exploratory studies based on blood marker detection as screening and efficacy evaluation of SCLC bone metastases have been reported in recent years. By reviewing the molecular biological mechanism of SCLC bone metastasis formation, this paper found that conventional diagnostic methods such as imaging and pathological biopsy were inadequate in SCLC bone metastasis. The changes in hyaluronic acid, protein biomarkers, non-coding RNA, and biomarkers in liquid biopsy were earlier than the changes in imaging, which had the advantages of simple operation and good repeatability. It provides a new idea and method for the early diagnosis of SCLC bone metastasis, which is worthy of clinical application.
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Nomogram for Predicting Efficacy and Prognosis After Chemotherapy for Advanced NSCLC.

PURPOSE: One major issue is the therapeutic effect following chemotherapy for non-small cell lung cancer (NSCLC). Although numerous risk factors have been identified and novel therapies have been developed, improving patient overall survival (OS) remains a crucial postoperative issue. This study aimed to develop a nomogram for accurately predicting the OS of patients with Stage III-IV NSCLC treated with chemotherapy. METHODS: The Department of Respiration at Tangdu Hospital, Air Force Medical University, prospectively collected data on 321 patients between January 2018 and December 2023. A week before treatment, the platelet-to-lymphocyte ratio (PLR), the neutrophil-to-lymphocyte ratio (NLR), and seven autoantibodies were measured using Youden's index, which was obtained using the ROC curve. The formula was used to compute the values of PLR and NLR. After using multifactor Cox regression analysis to identify risk factors, a nomogram was produced regarding the therapeutic effect following chemotherapy. The performance of the nomogram was assessed using a bootstrapped-concordance index and calibration plots. RESULT: It was determined that NLR, sex-determining region Y-box 2 (SOX2), adenosine triphosphate binding RNA deconjugase 4-5 (GBU4-5), and MAGE family member A1 (MAGEA1) were significantly associated factors that could be combined to accurately predict the therapeutic effect following chemotherapy. Utilizing these risk indicators, we were able to develop a nomogram that predicted the patients' survival at 1, 3, and 5 years. At 3 years, the area under the curve representing the expected survival probability was 0.762 (95% confidence interval 0.66-0.87). With a bootstrapped-concordance index of 0.762, the nomogram demonstrated good calibration. CONCLUSIONS: Our nomogram proved to be a valuable instrument in accurately predicting the overall survival of patients.

Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer.

Background: Enhancing the diagnostic efficacy of early-stage lung cancer is crucial for improving prognosis. The objective of this study was to ascertain dependable exosomal miRNAs as biomarkers for the diagnosis of lung cancer. Methods: Exosomal miRNA candidates were identified through miRNA sequencing and subsequently validated in various case-control sets using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The correlation between the expression of exosomal miRNAs and the clinicopathological features of lung cancer was investigated. To assess the diagnostic efficacy of exosomal miRNAs for lung cancer, the receiver operating characteristic (ROC) curve analysis was conducted. The optimal cutoff value of exosomal miRNAs was determined in the testing cohort and subsequently confirmed in the validation cohort. Results: The results showed that the expression of exosomal miR-1290 was significantly elevated, while that of miR-29c-3p was significantly decreased in the plasma of lung cancer patients, especially in those with early-stage lung cancer, compared to individuals with benign lung conditions (P < 0.01). Exosomal miR-1290 and miR-29c-3p demonstrated superior diagnostic efficacy compared to conventional tumor biomarkers in distinguishing between lung cancer and benign lung diseases, as evidenced by their respective area under the curve (AUC) values of 0.934 and 0.868. Furthermore, exosomal miR-1290 and miR-29c-3p exhibited higher diagnostic efficiency in early-stage lung cancer than traditional tumor markers, with AUC values of 0.947 and 0.895, respectively. Notably, both exosomal miR-1290 and miR-29c-3p displayed substantial discriminatory capacity in distinguishing between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as indicated by their respective AUC values of 0.810 and 0.842. Conclusions: The findings of this study provided evidence that exosomal miR-1290 and miR-29c-3p hold significant potential as biomarkers for the early detection of lung cancer, as well as for differentiating between NSCLC and SCLC.

Role of long pentraxin PTX3 in cancer.

Cancer has become a leading cause of death and disease burden worldwide, closely related to rapid socioeconomic development. However, the fundamental reason is the lack of comprehensive understanding of the mechanism of cancer, accurate identification of preclinical cancer, and effective treatment of the disease. Therefore, it is particularly urgent to study specific mechanisms of cancer and develop effective prediction and treatment methods. Long Pentraxin PTX3 is a soluble pattern recognition molecule produced by various cells in inflammatory sites, which plays a role as a promoter or suppressor of cancer in multiple tumors through participating in innate immune response, neovascularization, energy metabolism, invasion, and metastasis mechanisms. Based on this, this article mainly reviews the role of PTX3 in various cancers.

Microbiota aggravates the pathogenesis of Drosophila acutely exposed to vehicle exhaust.

Vehicle exhaust (VE) is the primary cause of urban air pollution, which adversely affects the respiratory system, exacerbates lung diseases, and results in high mortality rates. However, the underlying mechanism of the pathogenesis is largely unclear. Here, we developed a Drosophila model to systematically investigate the effects of VE on their health and physiology. We found that VE significantly impaired life span and locomotion in Drosophila. Interestingly, there was an increase in bacterial load in the guts upon VE exposure, suggesting VE is able to induce dysbiosis in the guts. Microbiota depletion can ameliorate the impairment of life span and locomotion. VE causes permeability of intestinal epithelial cells and increases proliferation of intestinal cells, suggesting VE disrupts intestinal homeostasis. We elucidate the underlying mechanism by which VE triggers Imd and DUOX gene expression. Taken together, this Drosophila model provides insight into the pathogenesis of Drosophila exposure to VE, enabling us to better understand the specific role of microbiota.

Photodynamic therapy for primary tracheobronchial malignancy in Northwestern China.

BACKGROUND: Photodynamic therapy (PDT) has been routinely performed to treat tracheobronchial malignancy. However, the experience in tracheobronchial adenoid cystic carcinoma (ACC) and peripheral lung cancer is still insufficient. This study aimed to share the experience of PDT for patients with primary tracheobronchial malignancy, especially the adenoid cystic carcinoma and peripheral lung cancer, and evaluated the efficacy and safety of PDT in Northwestern Chinese patients. METHODS: This study retrospectively analyzed the clinical data of 23 patients with primary tracheobronchial malignancy receiving PDT in our center. The short-term effect was evaluated by the objective tumor response and the clinical response. The long-term effect was estimated by recurrence-free survival (RFS). RESULTS: Of 23 patients, SR was achieved in 18 patients and MR in 3 patients. The clinical symptoms and the quality of life were significantly improved after PDT (P<0.05). And the mean RFS was 8.9 ± 1.9 months. SR for 6 cases of ACC were achieved with significant improvement of clinical symptoms and quality of life. No procedure-related complications appeared. And PDT was successfully performed for the peripheral lung cancer with the guidance of electromagnetic navigation bronchoscopy (ENB). CONCLUSIONS: This study demonstrated that PDT achieved satisfactory efficacy and safety for Northwestern Chinese patients with primary tracheobronchial malignancy. Patients with ACC can benefit from PDT. And ENB-guided PDT is a novel and available option for the peripheral lung cancer. In short, this study accumulated valuable experience for the application of PDT in Chinese patients with primary tracheobronchial malignancy.

Independent Risk Factors for the Dynamic Development of COVID-19: A Retrospective Study.

OBJECTIVE: To identify the risk factors for predicting the dynamic progression of COVID-19. METHODS: A total of 2321 eligible patients were included in this study from February 4 to April 15, 2020. Two illness conditions, including mild/moderate (M/M) subtype to severe/critical (S/C) and S/C to fatality, were classified. Clinical message was collected and compared, respectively. Kaplan-Meier method, Cox regression model and risk score system were used to predict disease progression in S/C COVID-19. RESULTS: A total of 112 of 1761 patients with M/M subtype were progressors (P) and 1649 non-progressors (NP). Increasing disease progression associated with higher levels of neutrophils count (HR=1.958, 95% CI=1.253-3.059, P=0.003), CK (HR=2.203, 95% CI=1.048-4.632, P=0.037), LDH (HR=3.309, 95% CI=2.083-5.256, P<0.001) and CRP (HR=2.575, 95% CI=1.638-4.049, P<0.001), and lower level of lymphocytes count (HR=1.549, 95% CI=1.018-2.355, P=0.041), as well as total lesion volume ratio greater than ≥10% (HR=2.286, 95% CI=1.451-3.601, P<0.001) on admission. In progression to fatality, 56 of the 672 S/C cases died and 616 survived. Increasing fatality associated with lower level of lymphocytes count (HR:2.060, 95% CI:1.000-4.242, P=0.050), higher levels of BUN (HR:2.715, 95% CI:1.539-4.790, P<0.001), CK-MB (HR:3.412, 95% CI:1.760-6.616, P<0.001), LDH (HR:5.578, 95% CI:2.317-13.427, P<0.001), and PT (HR:3.619, 95% CI:2.102-6.231, P<0.001). Furthermore, high risk of neutrophils count, lymphocytes count, CK, LDH, CRP, and total lesion volume ratio was powerfully correlated with the incidence of progression to S/C in patients with NS COVID-19 and high odds of lymphocytes count, BUN, CK-MB, LDH, and PT were significantly associated with death in patients with S/C COVID-19. In addition, the progression and mortality rates increased with increasing risk scores. CONCLUSION: Elevated LDH level and lymphopenia were independent predictors for COVID-19 sustainable management in classifying non-severe patients who progressed to severe condition and identifying S/C patients who deteriorated to fatal outcomes as well. Total lesion volume ratio ≥10% may provide early predictive evidence with COVID-19 patients at high risk of developing into S/C to improve prognosis.

Risk Factors for COVID-19 in Patients with Hypertension.

BACKGROUND: Hypertension, as the most common comorbidity for patients with coronavirus disease 19 (COVID-19), has resulted in cases with more severe symptoms and higher mortality. The risk factors associated with COVID-19 in patients with hypertension are unknown. METHODS: All the available and confirmed patients with COVID-19 from February 3 to March 10, 2020, were enrolled from Huoshenshan Hospital, Wuhan, China. The demographic characteristics, clinical manifestations, laboratory data, radiological assessments, and treatments on admission were extracted and compared. Univariate and multivariate logistic regression methods were used to explore risk factors associated with COVID-19 in patients with hypertension and the severity of the cohort. RESULTS: A total of 430 available patients with COVID-19 were enrolled in the study, including 151 eligible patients with COVID-19 and hypertension. After PSM analysis, 141 patients without hypertension and 141 cases with hypertension were well matched. Compared with cases without hypertension, patients with hypertension were more severe (28.4% vs. 12.1%, p=0.001). In multivariate analysis, we found that neutrophil count (OR: 1.471; p=0.001), coronary heart disease (OR: 5.281; p=0.011), and the level of K+ (OR: 0.273; p < 0.001) were associated with patients with hypertension. In addition, the percentage of pulmonary infection volume was larger in cases with hypertension (4.55 vs. 5.8, p=0.017) and was a high risk factor for severe COVID-19 in patients with hypertension (OR: 1.084; p < 0.001). CONCLUSION: On admission, coronary heart disease, neutrophil count, and the level of K+ were associated with COVID-19 patients with hypertension. The percentage of the pulmonary infection volume was significantly larger in COVID-19 patients with hypertension and was a risk factor for COVID-19 severity of the cohort.

Multi-nodule of large airway: tracheobronchopathia osteochondroplastica.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TO) is a benign rare disease characterized by multiple tracheobronchial nodules, which has not been clearly illuminated and there are no standard guidelines for TO management. The aim of this study was to clarify the clinical features and treatment outcomes of TO and provide basis for clinical diagnosis and treatment. METHODS: A total of 32,215 patients taken bronchoscopy were retrospectively reviewed to select patients diagnosed with TO. Clinical characteristics, bronchoscopic manifestations, CT images, histopathological features, treatments and clinical course were investigated. RESULTS: 13 male and 6 female were identified as TO. The average age was 47.42±12.12 years. The incidence rate of TO in our study by bronchoscopy was 0.06%. The most frequent manifestation was chronic cough. Based on bronchoscopic manifestations, patients were categorized as three groups: the largest proportion was group of Stage II (10/19), followed by Stage III (5/19) and Stage I (4/19). The positive rate of CT in stage I, stage II and stage III was 0%, 50%, 100%, respectively. Histopathological analysis presented inflammatory exudation, squamous metaplasia, submucosal cartilaginous and osseous deposition. Bronchoscopic intervention and inhaled corticosteroids were administered to subjects in stage II and III, which improved their life qualities to some degree. CONCLUSIONS: Not only multi-disciplinary cooperation of clinical, endoscopic and histological assessment, but also awareness are crucial to TO diagnosis, especially in early stage of TO, which was difficult to identify. The stage of TO based on bronchoscopic visualization might be applied to guide the choice of clinical treatment strategy.

Automated detection and quantification of COVID-19 pneumonia: CT imaging analysis by a deep learning-based software.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. METHODS: A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. RESULTS: CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. CONCLUSION: Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients.

SDFN: Segmentation-based deep fusion network for thoracic disease classification in chest X-ray images.

This study aims to automatically diagnose thoracic diseases depicted on the chest x-ray (CXR) images using deep convolutional neural networks. The existing methods generally used the entire CXR images for training purposes, but this strategy may suffer from two drawbacks. First, potential misalignment or the existence of irrelevant objects in the entire CXR images may cause unnecessary noise and thus limit the network performance. Second, the relatively low image resolution caused by the resizing operation, which is a common pre-processing procedure for training neural networks, may lead to the loss of image details, making it difficult to detect pathologies with small lesion regions. To address these issues, we present a novel method termed as segmentation-based deep fusion network (SDFN), which leverages the domain knowledge and the higher-resolution information of local lung regions. Specifically, the local lung regions were identified and cropped by the Lung Region Generator (LRG). Two CNN-based classification models were then used as feature extractors to obtain the discriminative features of the entire CXR images and the cropped lung region images. Lastly, the obtained features were fused by the feature fusion module for disease classification. Evaluated by the NIH benchmark split on the Chest X-ray 14 Dataset, our experimental result demonstrated that the developed method achieved more accurate disease classification compared with the available approaches via the receiver operating characteristic (ROC) analyses. It was also found that the SDFN could localize the lesion regions more precisely as compared to the traditional method.

Diagnosing a solitary pulmonary nodule using multiple bronchoscopic guided technologies: A prospective randomized study.

BACKGROUND: The rate of detection of pulmonary nodules on computed radiography (CR) is approximately 0.09-0.2%, so rapid identification of the nature of solitary pulmonary nodules (SPNs) with a likelihood of malignancy is a critical challenge in the early diagnosis of lung cancer. OBJECTIVE: We conducted this study to compare the diagnostic yield and safety of endobronchial ultrasonography with a guide sheath (EBUS-GS), and the combination of EBUS-GS and virtual bronchoscopic navigation (VBN). METHODS: This was a prospective, multicenter, multi-arm, randomized controlled trial involving a total of 1010 subjects. All the patients recruited underwent a chest CT scan which found SPNs that needed to be diagnosed. The subjects were randomly divided into one of three groups: a traditional, non-guided, bronchoscopy biopsy group (NGB group), an EBUS-GS guided bronchoscopy biopsy group (EBUS group), and a guided bronchoscopy biopsy group that combined EBUS-GS with VBN (combined group). The primary endpoint was to investigate the differences between the diagnostic yields of the three groups. RESULTS: There was no significant difference in the diagnostic yield between the EBUS group (72.3%) and the combined group (74.3%), but the diagnostic yield for the NGB group was 41.2%. The time required to reach biopsy position was significantly less in the combined group (7.96 ± 1.18 min in the combined group versus 11.92 ± 5.37 min in the EBUS group, p < 0.05). However, the bronchoscope operation time was the same in the EBUS-GS and combined groups. The diagnostic yield for peripheral pulmonary lesions (PPLs) >20 mm in diameter was significantly higher than for those <20 mm in diameter. CONCLUSION: The results of our study suggest that guided bronchoscopy could increase the diagnostic yield in the context of peripheral lesions. There was no significant difference in the diagnostic yield between the EBUS and combined groups, but use of EBUS-GS with VBN could significantly shorten the bronchoscope arrival time.

Downregulation of P38 phosphorylation correlates with low-grade differentiation and proliferation of lung squamous cell carcinoma.

BACKGROUND: P38MAPK has been investigated as a tumor-related signaling molecule because of its apparent association with tumorigenesis. This study aimed to investigate P38MAPK expression and its role in lung squamous carcinoma (LSCC). METHODS: The expression of P38MAPK and phosphorylated P38 (P-P38) in LSCC tissues and cells was examined by Western blot, real-time PCR, and immunohistochemistry. The influence of P38MAPK inhibitor SB203580 on the proliferation of LSCC cells was detected by MTT and flow cytometry. RESULTS: The expression of P-P38 in LSCC tissues and cells was lower than that in cancer-adjacent normal tissues and normal bronchial epithelial cells (P<0.05). In addition, the expression of P-P38 was downregulated in LSCC tissues of poor differentiation, stages III and IV, and with lymph node metastasis compared with the LSCC tissues of well differentiation, stages I and II, and without lymph node metastasis (P<0.05). Moreover, the cell proliferation of LSCC SK-MES-1 cells treated by P38MAPK inhibitor SB203580 significantly increased in a concentration-dependent manner compared with that of SK-MES-1 cells without SB203580 (P<0.05). The inhibition of P38MAPK promoted the transition of the S phase to the G2 phase. CONCLUSIONS: P-P38 was poorly expressed in LSCC tissues and cells. Its low expression was correlated with low-grade differentiation, lymph node metastasis, and advanced stage of LSCC. Inhibition of P38MAPK expression could significantly increase the proliferation of LSCC cells by promoting the transition of the S phase to the G2 phase.

Increased stathmin correlates with advanced stage and poor survival of non-small cell lung cancer.

BACKGROUND: Previous studies show that overexpression of stathmin involved in the malignant biological behavior of lung cancer. This investigation is to disclose the expression status of stathmin in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis and prognosis to lung cancer. METHODS: The expression of stathmin in cells and tissues of NSCLC was examined using immunohistochemistry (IHC), in-situ hybridization (ISH), and Western blot. The correlation between stathmin expression and survival of lung cancer patients was evaluated by a Kaplan-Meier method and the multiple regression analysis. RESULTS: NSCLC tissues and cells showed an overexpression of stathmin compared with normal lung tissues and cells (p< 0.05). And the expression level of stathmin was significantly associated with lung adenocarcinoma (LAC) (p< 0.05), lymphatic invasion (p< 0.05) and advanced stages of NSCLC (p< 0.05). Moreover, overexpression of stathmin predicted a reduced survival (p<0.05). CONCLUSION: Increased stathmin correlated with pathologic grade, lymphatic invasion, advanced stage and poor survival of NSCLC, which indicated that stathmin could serve as a potential biomarker of NSCLC.

Early Candidate Biomarkers of Non-Small Cell Lung Cancer Are Screened and Identified in Premalignant Lung Lesions.

A specific protein profile that accompanies neoplastic transformation in the premalignant airway epithelium could provide an opportunity for early diagnosis of lung cancer. The aim of this study was to screen and identify early candidate biomarkers of non-small cell lung cancer. Thirteen non-small cell lung cancer samples were obtained within 30 minutes after a surgical resection. Laser capture microdissection was performed to enrich the normal lung cell and squamous metaplasia or atypical adenomatous hyperplasia cell populations. The resulting tandem mass spectrum was automatically searched for proteins against International Protein Index (IPI) human protein database using the TurboSEQUEST searching engine. The molecular function and biological processes of identified proteins were determined based on universal bioinformatics tools. The 2 proteins of interest, focal adhesion kinase and C-terminal Src kinase, were validated using Western blot method. A total of 863 proteins were identified by automatically searching the tandem mass spectrum, among which 427 were dysregulated expression in premalignant airway epithelium compared with those of normal lung cells. The 427 proteins were mainly distributed in 24 sorts of cellular components, 22 molecular function, 15 biological processes, and 10 significant perturbations of pathways. The most significant network included 48 genes and was related to energy production, cell cytoskeleton, cell adhesion, metabolism, oxidative stress, and small molecule biochemistry. Focal adhesion kinase and C-terminal Src kinase were significantly overexpressed in premalignant lung lesion cells compared with the normal lung cells in 13 cases. We identified that there were 427 proteins involved in non-small cell lung cancer carcinogenic process and confirmed the key biological pathways in premalignant lung tissue. The significantly upregulated focal adhesion kinase and C-terminal Src kinase could be considered as molecular biomarkers for early diagnosis and prognosis of non-small cell lung cancer.

Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases.

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dose-dependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs.

3,5,4'-Tri-O-acetylresveratrol decreases seawater inhalation-induced acute lung injury by interfering with the NF-κB and i-NOS pathways.

Drowning is a cause of accidental mortality. However, survival may result in acute lung injury. The aim of the present study was to evaluate the effects of 3,5,4'-tri-O-acetylresveratrol (AC-Res) on acute lung injury (ALI) induced by seawater inhalation in rats. ALI models were established by the tracheal instillation of artificial seawater with or without 50 mg/kg AC-Res pretreatment for 7 days. Lung samples from different groups were harvested 4 h after the model was established. Histological changes, blood vessel permeability, inflammatory factor secretion and expression states of the nuclear factor-κB (NF-κB) and inducible NOS (i-NOS) pathway were assessed to evaluate seawater­induced lung injury and the protective effects of acetylated resveratrol. The results showed that seawater inspiration led to physiological structure changes and an increased permeability of blood vessels. In addition, seawater stimulation enhanced the expression levels of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-1 ß (IL-1ß) secretion in vitro and in vivo. Notably, seawater inhalation increased NF-κB and i-NOS expression in lungs and cells. On the other hand, pretreatment of AC-Res inhibited the abnormal expression of the NF-κB and i-NOS pathways, followed by decreased NO, TNF-α and IL-1ß secretion, protein and cell content in bronchoalveolar lavage fluid (BALF) and Evans blue, protein and cell infiltration from blood vessels into lung tissues. The results therefore suggest that AC-Res attenuated seawater inhalation induced­ALI by interfering with the NF-κB and i-NOS pathways.

Analysis of novel microRNA targets in drug-sensitive and -insensitive small cell lung cancer cell lines.

Advances in chemotherapy have failed to improve the long-term survival rate of small cell lung cancer (SCLC) patients due to multidrug resistance (MDR). The mechanisms of MDR are complex involving multiple genes and a variety of mechanisms. MicroRNAs (miRNAs) are non-coding RNAs theoretically involved in gene regulation. The aim of the present study was to explore the role of miRNAs in SCLC occurrence and multidrug resistance. Expression levels of known miRNAs in SCLC cell line H446 and its multidrug-resistant cell line H446/CDDP were analyzed using the next generation high through-put Illumina Solexa sequencing technology, and expression of a group of specific miRNAs was validated by quantitative polymerase chain reaction (qPCR). Furthermore, novel miRNAs and their putative target genes in the two SCLC cell lines were predicted with the help of software developed by Beijing Genomics Institute and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed a set of known miRNAs with altered expression in the H446 and H446/CDDP cells which may be associated with multidrug resistance of SCLC. Biological information analysis of the novel miRNAs and their putative target genes further elucidated the role of miRNAs in MDR. In addition, the pathway prediction by KEGG analysis may provide clues for further research on MDR of SCLC.

3,5,4'-Tri-O-acetylresveratrol Attenuates Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome via MAPK/SIRT1 Pathway.

The aim of the present research was to investigate the protecting effects of 3,5,4'-tri-O-acetylresveratrol (AC-Rsv) on LPS-induced acute respiratory distress syndrome (ARDS). Lung injuries have been evaluated by histological examination, wet-to-dry weight ratios, and cell count and protein content in bronchoalveolar lavage fluid. Inflammation was assessed by MPO activities and cytokine secretion in lungs and cells. The results showed that AC-Rsv significantly reduced the mortality of mice stimulated with LPS. Pretreatment of AC-Rsv attenuated LPS-induced histological changes, alleviated pulmonary edema, reduced blood vascular leakage, and inhibited the MPO activities in lungs. What was more, AC-Rsv and Rsv treatment reduced the secretion of TNF-α, IL-6, and IL-1ß in lungs and NR8383 cells, respectively. Further exploration revealed that AC-Rsv and Rsv treatment relieved LPS-induced inhibition on SIRT1 expression and restrained the activation effects of LPS on MAPKs and NF-κB activation both in vitro and in vivo. More importantly, in vivo results have also demonstrated that the protecting effects of Rsv on LPS-induced inflammation would be neutralized when SIRT1 was in-hibited by EX527. Taken together, these results indicated that AC-Rsv protected lung tissue against LPS-induced ARDS by attenuating inflammation via p38 MAPK/SIRT1 pathway.

Mitochondrial dysfunction rather than mtDNA sequence mutation is responsible for the multi-drug resistance of small cell lung cancer.

Small cell lung cancer (SCLC) accounts for ~15% of all lung cancer cases, and chemotherapy has dramatically improved the survival rate of SCLC patients. Yet, the long-term survival rate of this cancer has not improved since multi-drug resistance (MDR) may emerge after chemotherapy. Mitochondrial DNA (mtDNA) mutation-related biological processes, such as energy metabolism and reactive oxygen species (ROS) production, have been considered to be associated with tumorigenesis and drug resistance. It was hypothesized and demonstrated, in the present study, that mitochondrial dysfunction is the reason for the occurrence and progression of SCLC. mtDNA from drug sensitive and drug insensitive cell lines (H446 and H446/CDDP) was sequenced and compared with the revised Cambridge reference sequence (rCRS). The results revealed that there was no difference in the mtDNA sequence from H446 and H446/CDDP cells, but several spot mutations were observed according to that of rCRs. Further evaluation on mitochondrial function revealed that H446 cells synthesized and secreted more lactic acid and ROS compared with that of H446/CDDP cells when challenged by the same dose of cisplatin (P>0.05). In addition, examination of the mitochondrial apoptotic pathway indicated that more Bax, cleaved caspase-3 and cleaved caspase-9 were expressed in H446 cells compared with that of H446/CDDP cells when stimulated by the same dose of cisplatin (P>0.05). In conclusion, the results of the present study revealed that mtDNA mutations were responsible for the tumorigenesis of SLCL, but not associated with the drug sensitivity of SCLC cell lines. On the other hand, varied mitochondrium content­related mitochondrial dysfunction participated in the MDR of SCLC possibly by affecting the ROS-mediated mitochondrial apoptotic pathway.