STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/ß-catenin signaling pathway in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. METHODS: qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. RESULTS: JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G0/G1 phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/ß-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/ß-catenin pathway activator in A549 cells. CONCLUSIONS: Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.

LncRNA XIST acts as a MicroRNA-520 sponge to regulate the Cisplatin resistance in NSCLC cells by mediating BAX through CeRNA network.

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network. Methods: GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2. Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells. Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma.

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

Investigating the mechanism of ShuFeng JieDu capsule for the treatment of novel Coronavirus pneumonia (COVID-19) based on network pharmacology.

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective.

Integrative analysis of DNA methylation-driven genes for the prognosis of lung squamous cell carcinoma using MethylMix.

Background: DNA methylation acts as a key component in epigenetic modifications of genomic function and functions as disease-specific prognostic biomarkers for lung squamous cell carcinoma (LUSC). This present study aimed to identify methylation-driven genes as prognostic biomarkers for LUSC using bioinformatics analysis. Materials and Methods: Differentially expressed RNAs were obtained using the edge R package from 502 LUSC tissues and 49 adjacent non-LUSC tissues. Differentially methylated genes were obtained using the limma R package from 504 LUSC tissues and 69 adjacent non-LUSC tissues. The methylation-driven genes were obtained using the MethylMix R package from 500 LUSC tissues with matched DNA methylation data and gene expression data and 69 non-LUSC tissues with DNA methylation data. Gene ontology and ConsensusPathDB pathway analysis were performed to analyze the functional enrichment of methylation-driven genes. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of differentially methylated genes for predicting the prognosis of LUSC. Results: A total of 44 methylation-driven genes were obtained. Univariate and multivariate Cox regression analyses showed that twelve aberrant methylated genes (ATP6V0CP3, AGGF1P3, RP11-264L1.4, HIST1H4K, LINC01158, CH17-140K24.1, CTC-523E23.14, ADCYAP1, COX11P1, TRIM58, FOXD4L6, CBLN1) were entered into a Cox predictive model associated with overall survival in LUSC patients. Methylation and gene expression combined survival analysis showed that the survival rate of hypermethylation and low-expression of DQX1 and WDR61 were low. The expression of DQX1 had a significantly negatively correlated with the methylation site cg02034222. Conclusion: Methylation-driven genes DQX1 and WDR61 might be potential biomarkers for predicting the prognosis of LUSC.

Comprehensive analysis of TPX2-related ceRNA network as prognostic biomarkers in lung adenocarcinoma.

Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

Analysis of inflammatory parameters and disease severity for 88 hospitalized COVID-19 patients in Wuhan, China.

Background and aim: The outbreak of coronavirus disease 2019 (COVID-19) is quickly turning into a pandemic. We aimed to further clarify the clinical characteristics and the relationship between these features and disease severity. Methods: In this retrospective single-center study, demographic, clinical and laboratory data were collected and analyzed among moderate, severe and critically ill group patients. Results: 88 hospitalization patients confirmed COVID-19 were enrolled in this study. The average age of the patients was 57.11 years (SD, ±15.39). Of these 88 patients, the median body mass index (BMI) was 24.03 (IQR, 21.64-26.61; range 15.05-32.39), the median duration from disease onset to hospital admission were 11 days (IQR, 6.50-14.50). 46.59% patients had one or more comorbidities, with hypertension being the most common (26.14%), followed by diabetes mellitus (12.50%) and coronary atherosclerotic heart disease (CAD) (7.95%). Common symptoms at onset of disease were fever (71.59%), cough (59.09%), dyspnea (38.64%) and fatigue (29.55%). 88 patients were divided into moderate (47 [53.41%]), severe (32 [36.36%]) and critically ill (9 [10.23%]) groups. Compared with severe and moderate patients, lymphocytopenia occurred in 85.71% critically ill patients, and serum IL-2R, IL-6, IL-8, TNF-α, LDH, and cTnI were also increased in 71.42%, 83.33%, 57.14%, 71.43%, 100% and 42.86% in critically ill patients. Through our analysis, the age, comorbidities, lymphocyte count, eosinophil count, ferritin, CRP, LDH, PT and inflammatory cytokines were statistically significant along with the disease severity. Conclusion: We found some clinical characteristic and inflammatory cytokines could reveal the severity of COVID-19 during the outbreak phage. Our research could assist the clinicians recognize severe and critically ill patients timely and focus on the expectant treatment for each patient.

A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

BACKGROUND: Recently, circular RNAs (circRNAs) have been reported to be microRNA sponges and play essential roles in cancer development. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD). METHODS: The Gene Expression Omnibus (GEO) dataset was used to investigate differentially expressed circRNAs (DEcircRNAs) in paired LUAD tissues and adjacent nontumor tissues. The expression levels of the host genes were analyzed in The Cancer Genome Atlas (TCGA)-LUAD dataset, and the prognostic value was assessed using the Kaplan-Meier plotter. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of candidate circRNAs in the LUAD plasma and cells. The CCK8 assay was used to measure the function of circRNAs in cell proliferation. Competing endogenous RNA (ceRNA) network, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the possible mechanisms and functions of circRNAs in LUAD. RESULTS: Two upregulated and two downregulated circRNAs were identified as candidate circRNAs using bioinformatics analysis. qRT-PCR demonstrated that hsa_circ_0005962 was upregulated in LUAD plasma and cells, whereas hsa_circ_0086414 was downregulated. Receiver operating characteristic (ROC) curve analysis confirmed that a signature comprising the two circRNAs had good diagnostic potential, with an area under the ROC curve (AUC) of 0.81 (P < 0.0001). In addition, we observed that overexpression of plasma hsa_circ_0086414 was related to EGFR mutations (P = 0.001). Plasma hsa_circ_0005962 displayed significantly different expression before and after surgery in patients with LUAD (P < 0.0001). In vitro experiments suggested that hsa_circ_0005962 promoted LUAD cell proliferation. For future studies, we predicted the circRNA-miRNA-mRNA network for hsa_circ_0005962. Bioinformatics analysis revealed that hsa_circ_0005962 might be involved in LUAD development. CONCLUSION: A circRNA signature was identified as a potential noninvasive biomarker for LUAD diagnosis.

Methylation and transcriptome analysis reveal lung adenocarcinoma-specific diagnostic biomarkers.

BACKGROUND: DNA methylation can regulate the role of long noncoding RNAs (lncRNAs) in the development of lung adenocarcinoma (LUAD). The present study aimed to identify methylation-driven lncRNAs and mRNAs as biomarkers in the prognosis of LUAD using bioinformatics analysis. METHODS: Differentially expressed RNAs were obtained using the edge R package from 535 LUAD tissues and 59 adjacent non-LUAD tissues. Differentially methylated genes were obtained using the limma R package from 475 LUAD tissues and 32 adjacent non-LUAD tissues. Methylation-driven mRNA and lncRNA were obtained using the MethylMix R package from 465 LUAD tissues with matched DNA methylation and RNA expression and 32 non-LUAD tissues with DNA methylation. Gene ontology and ConsensusPathDB pathway analysis were performed to identify functional enrichment of methylation-driven mRNAs. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of each variable for predicting the prognosis of LUAD. Kaplan-Meier curve analysis of DNA methylation and gene expression might provide potential prognostic biomarkers for LUAD patients. RESULTS: A total of 99 methylation-driven mRNAs and 17 methylation-driven lncRNAs were obtained. Univariate and multivariate Cox regression analysis showed that 6 lncRNAs (FOXE1, HOXB13-AS1_2, VMO1, HIST1H3F, AJ003147.8, ASXL3) were retrieved to construct a predictive model associated with overall survival in LUAD patients. Combined DNA methylation and gene expression survival analysis revealed that 4 lncRNAs (AC023824.1, AF186192.1, LINC01354 and WASIR2) and 8 mRNAs (S1PR1, CCDC181, F2RL1, EFS, KLHDC9, MPV17L, GKN2, ITPRIPL1) might act as independent biomarkers for the prognosis of LUAD. CONCLUSIONS: Methylation-driven lncRNA and mRNA contribute to the survival of LUAD, and 4 lncRNAs and 8 mRNAs might be potential biomarkers for the prognosis of LUAD.

[Expert consensus statement on Pudilan Xiaoyan Oral Liquid in clinical practice].

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.

Elevated mRNA Levels of AURKA, CDC20 and TPX2 are associated with poor prognosis of smoking related lung adenocarcinoma using bioinformatics analysis.

Background and aim: Adenocarcinoma is a very common pathological subtype for lung cancer. We aimed to identify the gene signature associated with the prognosis of smoking related lung adenocarcinoma using bioinformatics analysis. Methods: A total of five gene expression profiles (GSE31210, GSE32863, GSE40791, GSE43458 and GSE75037) have been identified from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using GEO2R software and functional and pathway enrichment analysis. Furthermore, the overall survival (OS) and recurrence-free survival (RFS) have been validated using an independent cohort from the Cancer Genome Atlas (TCGA) database. Results: We identified a total of 58 DEGs which mainly enriched in ECM-receptor interaction, platelet activation and PPAR signaling pathway. Then according to the enrichment analysis results, we selected three genes (AURKA, CDC20 and TPX2) for their roles in regulating tumor cell cycle and cell division. The results showed that the hazard ratio (HR) of the mRNA expression of AURKA for OS was 1.588 with (1.127-2.237) 95% confidence interval (CI) (P=0.009). The mRNA levels of CDC20 (HR 1.530, 95% CI 1.086-2.115, P=0.016) and TPX2 (HR 1.777, 95%CI 1.262-2.503, P=0.001) were also significantly associated with the OS. Expression of these three genes were not associated with RFS, suggesting that there might be many factors affect RFS. Conclusion: The mRNA signature of AURKA, CDC20 and TPX2 were potential biomarkers for predicting poor prognosis of smoking related lung adenocarcinoma.

A novel nomogram model for lung adenocarcinoma subtypes based on RNA-modification regulatory genes.

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research. Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways. Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

Pan-cancer prognosis, immune infiltration, and drug resistance characterization of lung squamous cell carcinoma tumor microenvironment-related genes.

Background: The tumor microenvironment (TME) plays an important role in cancer development; however, its implications in lung squamous cell carcinoma (LUSC) and pan-cancer have been poorly understood. Methods: In this study, The Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissue using Expression Data (ESTIMATE) datasets were applied to identify differentially expressed genes. Additionally, online public databases were utilized for in-depth bioinformatics analysis of pan-cancer datasets to investigate the prognostic implications of TME-related genes further. Results: Our study demonstrated a significant association between stromal scores, immune scores, and specific clinical characteristics in LUSC patients. C3AR1, CSF1R, CCL2, CCR1, and CD14 were identified as prognostic genes related to the TME. All TME-related prognostic genes demonstrated varying degrees of correlation with immune infiltration subtypes and tumor cell stemness. Moreover, our study revealed that TME-related prognostic genes, particularly C3AR1 and CCR1, might contribute to drug resistance in cancer cells. Conclusions: The identified TME-related prognostic genes, particularly C3AR1 and CCR1, have potential implications for understanding and targeting drug resistance mechanisms in cancer cells.

YuPingFeng (YPF) upregulates caveolin-1 (CAV1) to alleviate pulmonary fibrosis through the TGF-ß1/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) is considered a valuable asset in China's medical tradition. YPF is a classic prescription that has been derived from the "Jiu Yuan Fang" formula and consists of three herbs: Huangqi (Astragalus membranaceus Bunge), Baizhu (Atractylodes rubra Dekker), and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk). This prescription is widely acclaimed for its exceptional pharmacological properties, including potent antioxidant effects, hormone regulation, and immune modulation effects. AIM OF THE STUDY: Previous research provides evidence suggesting that YPF may have therapeutic effects on pulmonary fibrosis. Further exploration is essential to confirm its effectiveness and elucidate the fundamental processes. MATERIALS AND METHODS: First, the active components and target genes of YPF were extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Next, the GSE53845 dataset, which contains information on pulmonary fibrosis, was downloaded from the GEO database. Network informatics methods was then be utilized to identify target genes associated with pulmonary fibrosis. A YPF-based network of protein-protein interactions was constructed to pinpoint possible target genes for pulmonary fibrosis treatment. Additionally, an in vitro model of pulmonary fibrosis induced by bleomycin (BLM) was established to further investigate and validate the possible mechanisms underlying the effectiveness of YPF. RESULTS: In this study, a total of 24 active ingredients of YPF, along with 178 target genes associated with the treatment, were identified. Additionally, 615 target genes related to pulmonary fibrosis were identified. Functional enrichment analysis revealed that 18 candidate genes (CGs) exhibited significant responses to tumor necrosis factor, NF-kB survival signaling, and positive regulation of apoptosis processes. Among these CGs, CAV1, VCAM1, and TP63 were identified as key target genes. Furthermore, cell experiments confirmed that the expression of CAV1 protein and RNA expression was increased in pulmonary fibrosis, but significantly decreased after treatment with YPF. Additionally, the expression of pSmad2, α-SMA, TGF-ß1, and TNF-α was also decreased following YPF treatment. CONCLUSIONS: Network pharmacology analysis revealed that YPF exhibits significant potential as a therapeutic intervention for pulmonary fibrosis by targeting various compounds and pathways. This study emphasizes that the efficacy of YPF in treating pulmonary fibrosis may be attributed to its ability to up-regulate CAV1 expression and inhibiting pulmonary fibrosis via modulation of the TGF-ß1/Smad2 signaling pathway. These findings underscore the promising role of YPF and its ability to potentially alleviate pulmonary fibrosis.

IDO1 Promotes the Progression of NSCLC by Regulating the Polarization of M2 Macrophages.

Purpose: Non-small cell lung cancer (NSCLC) is currently a problem in the clinic and in society. Tumor-related macrophages (TAMs) in the tumor microenvironment (TME) play a vital role in the development of NSCLC. Patients and Methods: Bioinformatics was used to analyze the role of Indoleamine 2,3-dioxygenase 1 (IDO1) in NSCLC and the correlation of its expression with CD163 expression. The expression of CD163 and IDO1 was measured by immunohistochemistry, and their colocalization was assessed by immunofluorescence. M2 macrophage polarization was induced, and a coculture model of NSCLC cells and macrophages was established. Results: Bioinformatics analysis showed that IDO1 promoted the metastasis and differentiation of NSCLC and inhibited DNA repair. Moreover, the expression of IDO1 was positively correlated with CD163 expression. We discovered that IDO1 expression was related to M2 macrophage differentiation. In vitro, we showed that increased IDO1 expression promoted the invasion, proliferation, and metastasis of NSCLC cells. Conclusion: In conclusion, we determined that IDO1 can regulate the M2 polarization of TAMs and promote the progression of NSCLC, which provides partial theoretical evidence for the use of IDO1 inhibitors in the treatment of NSCLC.

Giant pulmonary sclerosing pneumocytoma with potentially malignant biological behavior: a case report and literature review.

Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign lung tumor which generally presents as a solitary pulmonary nodule in middle-aged females. However, the PSP in some patients exhibits potentially malignant biological behavior, with recurrence and lymphatic or distant metastasis being observed. Case Description: We encountered a case of a 46-year-old female with an inordinately massive tumor 9.5 cm in diameter and a relatively high Ki-67 proliferation rate. Fine needle aspiration (FNA) played a significant but limited role in the preoperative diagnosis: the computed tomography (CT)-guided lung puncture biopsy was consistent with the typical pathology of PSP; however, endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) could not provide a definitive diagnosis. The patient ultimately underwent thoracoscopic resection and mediastinal lymph node dissection. Here, we provide a review of the literature on patients with PSP with malignant biological behavior to raise awareness of the malignant potential of PSP and describe our experience to inform future management. Conclusions: PSP lacks specificity in its clinical and radiological characteristics and has complex pathological manifestations. FNA is valuable in the diagnosis and differential diagnosis of PSP but involves the risk of misdiagnosis or missed diagnosis. Additionally, we believe that the accepted benign features of PSP need to be updated and that the potential malignant features of PSP should be carefully monitored. Surgical resection is curative but strict follow-up is crucial.

Autophagy-related tumor subtypes associated with significant gene expression profiles and immune cell infiltration signatures to reveal the prognosis of non-small cell lung cancer.

Autophagy plays an important role in non-small cell lung cancer (NSCLC). We aimed to establish novel autophagy-related tumor subtypes to distinguish the prognosis of NSCLC. In this study, gene expression profiles, mutation data and clinical information obtained from the Cancer Genome Atlas. Kaplan Meier-plotter could evaluate prognostic value of autophagy-related genes. Consensus clustering revealed autophagy-related tumor subtypes. Gene expression profiles, mutation data and immune infiltration signatures were identified, oncogenic pathways and gene-drug interactions were performed according to the clusters. Finally, a total of 23 prognostic genes were screened and consensus clustering analysis divided the NSCLC into 2 clusters. The mutation signature showed that 6 genes are special. Immune infiltration signatures showed that higher fraction of immune cells was associated with cluster 1. The oncogenic pathways and gene-drug interactions also showed different patterns. In conclusion, autophagy-related tumor subtypes have different prognosis. Understanding the subtypes of NSCLC are helpful to accurately identify the NSCLC and personalized treatment.

The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with an extremely poor prognosis. Autophagy is a fundamental intracellular process involved in maintaining cellular homeostasis and regulating cell survival. Autophagy deficiency has been shown to play an important role in the progression of pulmonary fibrosis. This review focused on the six steps of autophagy, as well as the interplay between autophagy and other seven pulmonary fibrosis related mechanisms, which include extracellular matrix deposition, myofibroblast differentiation, epithelial-mesenchymal transition, pulmonary epithelial cell dysfunction, apoptosis, TGF-ß1 pathway, and the renin-angiotensin system. In addition, this review also summarized autophagy-related signaling pathways such as mTOR, MAPK, JAK2/STAT3 signaling, p65, and Keap1/Nrf2 signaling during the development of IPF. Furthermore, this review also illustrated the commonly used autophagy detection methods, the currently approved antifibrotic drugs pirfenidone and nintedanib, and several prospective compounds targeting autophagy for the treatment of IPF.

Identification and Validation of CDKN1A and HDAC1 as Senescence-Related Hub Genes in Chronic Obstructive Pulmonary Disease.

Purpose: Cellular senescence participates in the occurrence and development of chronic obstructive pulmonary disease (COPD). This study aimed to identify senescence-related hub genes and explore effective diagnostic markers and therapeutic targets for COPD. Methods: The microarray data from the GSE38974 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes between genes from the GSE38974 dataset and CellAge database were considered differentially expressed senescence-related genes (DESRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R software. Protein-protein interaction (PPI), miRNA-mRNA network, and competitive endogenous RNA (ceRNA) network were constructed and visualized by Cytoscape software. GSE100281 and GSE103174 datasets were employed to validate the expression and diagnostic value of hub genes. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of hub genes in peripheral blood mononuclear cells (PBMCs) from COPD and control samples. Results: A total of 23 DESRGs were identified between COPD samples and healthy controls. Enrichment analysis revealed that DESRGs were mainly related to apoptosis and senescence. Moreover, four hub genes and two key clusters were acquired by Cytohubba and MCODE plugin, respectively. CDKN1A and HDAC1 were verified as final hub genes based on GSE100281 and GSE103174 datasets validation. The mRNA expression level of CDKN1A was negatively related to forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), and HDAC1 expression had the opposite correlation. Finally, an HDAC1-based ceRNA network, including 6 miRNAs and 11 lncRNAs, was constructed. Conclusion: We identified two senescence-related hub genes, CDKN1A and HDAC1, which may be effective biomarkers for COPD diagnosis and treatment. An HDAC1-related ceRNA network was constructed to clarify the role of senescence in COPD pathogenesis.