ABSTRACT
Background: The severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19. Methods: A control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored. Results: Compared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8-15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group. Conclusions: The levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.
Subject(s)
Angiotensin-Converting Enzyme 2 , Axl Receptor Tyrosine Kinase , Biomarkers , COVID-19 , Disease Progression , Proto-Oncogene Proteins , Receptor Protein-Tyrosine Kinases , SARS-CoV-2 , Humans , COVID-19/blood , COVID-19/immunology , COVID-19/diagnosis , Receptor Protein-Tyrosine Kinases/blood , Receptor Protein-Tyrosine Kinases/immunology , Male , Proto-Oncogene Proteins/blood , Female , Angiotensin-Converting Enzyme 2/blood , Biomarkers/blood , Middle Aged , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , Immunoglobulin G/blood , Severity of Illness Index , Immunoglobulin M/blood , ROC CurveABSTRACT
Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers' and 289 LUAD patients' serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.
Subject(s)
Adenocarcinoma of Lung , Exosomes , Lung Neoplasms , Melanoma , Male , Humans , Testis , Adenocarcinoma of Lung/genetics , Biomarkers , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , RNA, Messenger/genetics , Prognosis , Antigens, Neoplasm/genetics , Neoplasm Proteins/geneticsABSTRACT
Hydrogels hold great promise as electrolytes for emerging aqueous batteries, for which establishing a robust electrode-hydrogel interface is crucial for mitigating side reactions. Conventional hydrogel electrolytes fabricated by ex situ polymerization through either thermal stimulation or photo exposure cannot ensure complete interfacial contact with electrodes. Herein, we introduce an in situ electropolymerization approach for constructing hydrogel electrolytes. The hydrogel is spontaneously generated during the initial cycling of the battery, eliminating the need of additional initiators for polymerization. The involvement of electrodes during the hydrogel synthesis yields well-bonded and deep infiltrated electrode-electrolyte interfaces. As a case study, we attest that, the in situ-formed polyanionic hydrogel in Zn-MnO2 battery substantially improves the stability and kinetics of both Zn anode and porous MnO2 cathode owing to the robust interfaces. This research provides insight to the function of hydrogel electrolyte interfaces and constitutes a critical advancement in designing highly durable aqueous batteries.
ABSTRACT
Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. It is essential to explore the immune response characteristics of peripheral circulation in COVID-19 patients to reveal pathogenesis and predict disease progression. In this study, the levels of total immunoglobulins (IgG, IgM, IgA), complement (C3, C4)ï¼lymphocyte subsets (CD3+ cellï¼CD4+ cellï¼CD8+ cell, NK cell, CD19+ cell and CD45+ cell) and cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-12p, IL-1ß, TNF-α, IFN-α and IFN-γ) were retrospectively analyzed in COVID-19 patients. A total of 513 patients were enrolled in this study, cases were distributed according to clinical status as mild or moderate (n = 212), severe survivors (n = 197) and severe non-survivors (n = 104). IL-6, IL-8, IL-10 and IFN-γ were increased in severe patients compared with non-severe patients, despite decreased CD45+ cell, CD3+ cell, CD4+ cell, CD8+ cell, CD19+ cell, and NK cell. Compared with severe survivors, the levels of L-6, IL-8 and IL-10 in non-survivors increased significantly, and levels of C3, CD45+ cell, CD3+ cellï¼CD4+ cellï¼CD8+ cell, and NK cell decreased. Moreover, age, IL-8, IL-10, CD8+cells and NK cell were independent risk factors for the severity of COVID-19. Multivariable regression showed increasing odds ratio of in-hospital death associated with tumor, older age, higher IL-8 level, and decreasing odds ratio of in-hospital death associated with increased levels of CD8+cell and NK cell. Finally, patients with tumor, or high IL-6 or high IL-10 expression and lower CD8+ or lower NK levels exhibited a significantly shorter survival time. In conclusion, our study provides findings of the immunological characteristics associated with disease severity to predict the progression of COVID-19. The immune inflammation factors, such as IL-6, IL-8, IL-10, CD8+ cell and NK cell, could serve as excellent biomarkers for monitoring or predicting COVID-19 progression therapeutic to COVID-19 patients.
ABSTRACT
Rechargeable aqueous Zn-I2 batteries (ZIB) are regarded as a promising energy storage candidate. However, soluble polyiodide shuttling and rampant Zn dendrite growth hamper its commercial implementation. Herein, a hetero-polyionic hydrogel is designed as the electrolyte for ZIBs. On the cathode side, iodophilic polycationic hydrogel (PCH) effectively alleviates the shuttle effect and facilitates the redox kinetics of iodine species. Meanwhile, polyanionic hydrogel (PAH) toward Zn metal anode uniformizes Zn2+ flux and prevents surface corrosion by electrostatic repulsion of polyiodides. Consequently, the Zn symmetric cells with PAH electrolyte demonstrate remarkable cycling stability over 3000 h at 1 mA cm-2 (1 mAh cm-2 ) and 800 h at 10 mA cm-2 (5 mAh cm-2 ). Moreover, the Zn-I2 full cells with PAH-PCH hetero-polyionic hydrogel electrolyte deliver a low-capacity decay of 0.008 per cycle during 18 000 cycles at 8 C. This work sheds light on hydrogel electrolytes design for long-life conversion-type aqueous batteries.
ABSTRACT
Zinc finger CCHC-type containing 4 (ZCCHC4), RNA binding protein, has been reported to mediate rRNA methylation and affect tumor cell proliferation. However, the role of ZCCHC4 in the regulation of osteosarcoma (OS) remains unknown. ZCCHC4 was highly expressed in OS tissues and cell lines. Overexpression or silencing of ZCCHC4 promoted or inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and motility. Additionally, we proved that ZCCHC4 facilitates OS progression through upregulating integrin ß1 (ITGB1). In the animal model, ZCCHC4 knockdown reduced OS tumor growth and metastases in vivo. Our findings showed that ZCCHC4 promoted the progression of OS through upregulating ITGB1 and suggested that inhibition of ZCCHC4 could be a novel therapeutic strategy for OS.
Subject(s)
Bone Neoplasms , Osteosarcoma , Animals , Integrin beta1/genetics , Osteosarcoma/genetics , Cell Line , Cell Proliferation/genetics , Bone Neoplasms/geneticsABSTRACT
HEMGN belongs to the Cancer/testis antigens (CTAs), which are expressed in various types of human cancers and have received particular attention in cancer immunotherapy. However, the potential function of HEMGN involved in lung cancer and the immune response is not yet elucidated. HEMGN expression in lung adenocarcinoma (LUAD) was estimated via the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and Human Protein Atlas databases. The prognostic role of HEMGN was investigated by Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and Kaplan-Meier plotter databases. The associations between HEMGN and clinicopathological parameters were analyzed with UALCAN database. Then, immunohistochemical and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) analysis were performed to further verify the associations in tissue or serum samples. Serum from patients were detected for HEMGN antibody by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect immune cell infiltration in peripheral blood of patients with LUAD. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to investigate the functional role of HEMGN. Furthermore, we obtained the somatic mutation data from the TCGA LUAD dataset and analyzed the mutation profiles with "maftools" package. Finally, we evaluated the associations between HEMGN and immune infiltration level and the characteristic markers of immune cells in TIMER, GEPIA, and CIBERSORT. The mRNA and protein expressions of HEMGN were significantly decreased in LUAD patients. High HEMGN expression was remarkably associated with better prognosis in LUAD patients. The concentration levels of anti-HEMGN antibody in LUAD were significantly higher than that in healthy individuals and were closely correlated with clinical stage. In addition, HEMGN was involved in distinct typical genomic alterations in LUAD. GSEA demonstrated that HEMGN was significantly connected with immunity and substance metabolism. Notably, HEMGN was significantly related to immune infiltrates, including B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, dendritic cells (DCs), and various kinds of functional T cells. Furthermore, HEMGN had a significant association with diverse immune gene markers. HEMGN can be considered as a prognostic biomarker of LUAD and is associated with immune infiltration.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Male , Humans , Prognosis , Testis , Adenocarcinoma of Lung/genetics , Lung Neoplasms/genetics , Antibodies , Nuclear ProteinsABSTRACT
Objective: TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are recognized as novel and potential types of non-coding RNAs (ncRNAs), and several tRF/tiRNA signatures are closely associated with tumor diagnosis. This study aimed to analyze the expression profiles of plasma tRFs/tiRNAs and to clarify their diagnostic value in lung adenocarcinoma (LUAD). Methods: The differential expression profiles of plasma tRFs/tiRNAs in patients with four patients with early LUAD, four patients with advanced LUAD, and four healthy controls were analyzed using high-throughput sequencing technology. Then, plasma tRFs/tiRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and their diagnostic efficiency was appraised by receiver operating characteristic curve analysis. The correlation of candidate plasma tRFs/tiRNAs with clinicopathological features was also analyzed. Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs. Results: The sequencing results revealed that tRFs/tiRNAs from plasma samples in patients with LUAD were differently expressed, supporting the necessity of exploring their potential as biomarkers. The validation results of qRT-PCR demonstrated that the expression level of tRF-1:29-Pro-AGG-1-M6 was downregulated in LUAD, while that of tRF-55:76-Tyr-GTA-1-M2 was upregulated, which was consistent with the sequencing data. The areas under the receiver operating characteristic curve of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 were 0.882 and 0.896, respectively, which have significant values in the diagnosis of LUAD. The expressions of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 in LUAD were obviously correlated with various clinicopathological features such as tumor-node-metastasis stage, node stage, and the expression levels of carcinoembryonic antigen. In addition, their expression was significantly altered from before to after tumor resection in LUAD patients. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further indicated that tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 are widely distributed and apparently enriched in several tumor-related signaling pathways. Conclusions: Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 may be promising components in the development of highly sensitive and non-invasive biomarkers for LUAD diagnosis.
ABSTRACT
BACKGROUND: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. METHODS: The differential expression profile of plasma exosomal mRNA was established by high-throughput sequencing, and the expression and diagnostic value of plasma exosomal CXCL7 mRNA and protein in LUAD were studied to evaluate their diagnostic value as tumor biomarkers. RESULTS: The expression of plasma exosomal CXCL7 mRNA in patients with LUAD was significantly increased (p < 0.01), which had no significant correlation with age, gender, and stage. ROC was used to evaluate the diagnostic value of plasma exosomal CXCL7 mRNA in LUAD patients with AUC = 0.7171. Further analysis signified that the CXCL7 protein of plasma exosomes in LUAD patients was overexpressed, and it was positively correlated with TNM stage and age. The diagnostic value of plasma exosomal CXCL7 in LUAD is better than serum CEA, with an AUC of 0.785, which has higher sensitivity and specificity. CONCLUSIONS: This research suggests that plasma exosomal CXCL7 may become an effective biomarker for early diagnosis of LUAD.
Subject(s)
Adenocarcinoma of Lung , Exosomes , Lung Neoplasms , Adenocarcinoma of Lung/diagnosis , Biomarkers, Tumor/genetics , Exosomes/metabolism , Humans , Lung Neoplasms/pathology , RNA, Messenger/geneticsABSTRACT
BACKGROUND: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated. METHODS: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro. RESULTS: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result. CONCLUSION: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.
Subject(s)
Adenocarcinoma of Lung , Aspartate-tRNA Ligase , Lung Neoplasms , Adenocarcinoma of Lung/pathology , Aspartate-tRNA Ligase/genetics , Aspartate-tRNA Ligase/metabolism , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , PrognosisABSTRACT
OBJECTIVE: Although diabetes mellitus (DM) is considered to be an important prognostic factor in spinal surgery, the relationship between these two factors remains unclear. The purpose of this study was to investigate whether diabetes is associated with an increased risk of postoperative complications in patients undergoing spinal surgery. METHODS: We systematically searched the PubMed, Embase, and Cochrane Library for relevant articles published on or before December 25, 2021. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis. The primary outcome was the risk of postoperative complications following spinal surgery, including postoperative infection and reoperation. Furthermore, we conducted subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: A total of 40 cohort studies including 2,998,891 participants met the inclusion criteria. Meta-analysis showed that diabetes was significantly associated with postoperative infection (OR 2.21, 95% CI 1.70-2.88, p < 0.001) and reoperation (OR 1.35, 95% CI 1.12-1.64, p = 0.002). Furthermore, the results also found that diabetes was significantly associated with surgery-related death (OR 1.61, 95% CI 1.13-2.30, p = 0.008) and transfusions (OR 1.39, 95% CI 1.11-1.75, p = 0.005), whereas diabetes failed to account for nervous system complications (OR 1.12, 95% CI 0.82-1.52, p = 0.470) and embolism (OR 1.15, 95% CI 0.83-1.60, p = 0.386) for patients following spine surgery. These results were further confirmed by the trim-and-fill procedure and leave-one-out sensitivity analyses. CONCLUSIONS: Diabetes appears to be a risk factor for postoperative infection and reoperation for patients following spinal surgery. Special attention should be devoted to reducing the occurrence of postoperative complications in diabetic patients undergoing spinal surgery.
Subject(s)
Diabetes Mellitus , Humans , Neurosurgical Procedures , Postoperative Complications , Postoperative Period , ReoperationABSTRACT
Sideroflexin 1 (SFXN1) functions as a mitochondrial serine transporter in one-carbon metabolism. The association between SFXN1 and tumorigenesis remains to be elucidated. This study illustrated the functional role of SFXN1 in lung adenocarcinoma (LUAD). SFXN1 expression in LUAD specimens was examined using western blotting and quantitative real-time PCR (qRT-PCR), and the prognostic value between SFXN1 and clinicopathological parameters was investigated. Subsequently, the effects of SFXN1 on cellular proliferation, migration, and apoptosis were assessed by using Transwell assays and flow cytometry in A549 and H1299 cell lines. Western blotting was also employed to explore the mechanism of tumor progression. SFXN1 was significantly elevated in the LUAD samples compared with the para-carcinoma tissues. Furthermore, SFXN1 expression was an independent prognostic predictor for patients with LUAD. The expression of SFXN1 was altered in A549 and H1299 cell lines and this showed that SFXN1 promoted cell proliferation, migration, and invasion and inhibited apoptosis. SFXN1, at least partially, influenced LUAD progression via the mTOR signaling pathway. Collectively, the findings from this study demonstrated that SFXN1 promotes LUAD progression via the mTOR pathway and that SFXN1 expression is associated with clinicopathological features of LUAD. SFXN1 significantly contributes to the development of LUAD and might have potential, not only as an independent prognostic marker of LAUD but also as a promising target for LUAD therapy.
Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Humans , Adenocarcinoma/genetics , Adenocarcinoma of Lung/pathology , Carbon/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology , Prognosis , Serine/metabolism , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. METHODS: In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. RESULTS: The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. CONCLUSIONS: In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.
Subject(s)
Adenocarcinoma of Lung , Antigens, Neoplasm/metabolism , Lung Neoplasms , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/metabolism , Carcinoembryonic Antigen , Humans , Lung Neoplasms/pathology , Male , Prognosis , Testis/metabolismABSTRACT
Background: Circular RNAs (circRNAs) play an important role in tumorigenesis and several circulating circRNA signatures are closely associated with tumor diagnosis. However, the expression and clinical significance of the two forms of circulating circRNAs, serum and serum exosomal, in patients with lung adenocarcinoma (LUAD), have not been characterized. Methods: Three differentially expressed exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were selected based on previous exosomal circRNA sequencing data analyses of LUAD patients. The expression of these circRNAs in serum and serum-derived exosomes of LUAD patients was assessed using quantitative real-time PCR (qRT-PCR), and correlations between circRNA expression and clinicopathological characteristics were analyzed. The reliability of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 to diagnose LUAD was evaluated using receiver operating characteristic (ROC) analysis. Results: Expression of serum and serum exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 were significantly higher in LUAD patients than in healthy donors, and significantly lower after surgery. These three serum exosomal circRNAs were also associated with a higher cancer stage. Exosomal hsa_circ_0001492 expression was positively correlated with carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) levels. An association between the expression of the three serum circRNAs and clinical characteristics was not observed. In addition, the three serum exosomal circRNAs had higher diagnostic sensitivity and specificity than the serum circRNAs, and the area under the curve (AUC) of all three serum exosomal circRNAs was >0.75. The combination of exosomal hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 had better diagnostic sensitivity and specificity than that of a single marker, with an AUC value of 0.805. Conclusions: The serum and serum exosomal circRNAs, hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896, were upregulated in LUAD patients. Serum exosomal circRNAs may serve as more effective biomarkers than serum circRNAs for LUAD diagnosis and may further aid the detection of this disease.
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Most studies on the corrosion inhibition performance of organic molecules and (nano)materials were conducted within "carbon steel/1.0 M HCl" solution system using similar experimental and theoretical methods. As such, the numerous research findings in this system are sufficient to conduct comparative studies to select the best-suited inhibitor type that generally refers to a type of inhibitor with low concentration/high inhibition efficiency, nontoxic properties, and a simple and cost-economic synthesis process. Before data collection, to help readers have a clear understanding of some crucial elements for the evaluation of corrosion inhibition performance, we introduced the mainstay of corrosion inhibitors studies involved, including the corrosion and inhibition mechanism of carbon steel/HCl solution systems, evaluation methods of corrosion inhibition efficiency, adsorption isotherm models, adsorption thermodynamic parameters QC calculations, MD/MC simulations, and the main characterization techniques used. In the classification and statistical analysis section, organic compounds or (nano)materials as corrosion inhibitors were classified into six types according to their molecular structural characteristics, molecular size, and compound source, including drug molecules, ionic liquids, surfactants, plant extracts, polymers, and polymeric nanoparticles. We outlined the important conclusions obtained from recent literature and listed the evaluation methods, characterization techniques, and contrastable experimental data of these types of inhibitors when used for carbon steel corrosion in 1.0 M HCl solution. Finally, statistical analysis was only performed based on these data from carbon steel/1.0 M HCl solution system, from which some conclusions can contribute to reducing the workload of the acquisition of useful information and provide some reference directions for the development of new corrosion inhibitors.
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BACKGROUND: Sarcopenia is a progressive age-related skeletal muscle disorder characterized by decreased muscle mass and loss of muscle function. Recent studies have shown that sarcopenia is able to predict a variety of clinical outcomes after spinal surgery. Controversy still exists among previous reports in terms of the definition and measurement of sarcopenia, these findings are heterogeneous so far. Therefore, the aim of the current study is to assess the up-to-date evidence of sarcopenia for postoperative outcomes among people undergoing spinal surgery. METHODS AND ANALYSIS: This protocol was carried out based on the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. It has been pre-registered in PROSPERO with the registration number of CRD42021260459. Three databases (including Pubmed, EMBASE, and Cochrane Library) will be searched from inception through May 10, 2021 to determine related cohort studies examining sarcopenia on multidimensional outcomes in patients undergoing spinal surgery. Major outcomes will be involved including mortality, morbidity, length of stay, postoperative complications or adverse events. DerSimonian & Laird random-effects meta-analysis will be used to calculate pooled odds ratio (OR) for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias of included studies. Narrative synthesis will be carried out if a pooled analysis is not possible. ETHICS AND DISSEMINATION: Ethical approval is not required for this study as the data involved are from the published literatures. We intend to disseminate or share the results of the study in a peer-reviewed journal or at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021260459.
Subject(s)
Sarcopenia , Humans , Meta-Analysis as Topic , Morbidity , Postoperative Period , Research Design , Sarcopenia/complications , Systematic Reviews as TopicABSTRACT
Background: Lung cancer (LC) is ranked as a leading cause of cancer-related death worldwide. However, there are still few reliable screening biomarkers for daily clinical practice in LC. Circular RNAs (circRNAs) have been suggested as valuable diagnostic biomarkers in various cancers. In this study, the expression and diagnostic potential of several circRNAs for LC were explored. Methods: Seventy-two pairs of LC tissues and adjacent normal lung tissues were collected to measure the relative expression level of circRNAs using quantitative reverse transcription-polymerase chain reaction. In addition, the relationships between circRNAs and the clinicopathological features of LC patients were analyzed. Furthermore, the sensitivities and specificities of the circRNAs were evaluated by receiver operating characteristic (ROC) analysis. Results: The expression levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, has_circ_0074368, and has_circ_0000896 were downregulated in LC tissues compared with adjacent normal lung tissues. The lower levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, and has_circ_0000896 were significantly correlated with advanced disease stages. The area under the ROC curves of has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 were 0.833, 0.793, 0.773, 0.730, and 0.645, respectively. Conclusions: Has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 are capable of distinguishing LC tissues from normal lung tissues. Besides, the biggest area under the ROC curve value of has_circ_000249 suggests it appears to be a better diagnosis marker for LC patients.
Subject(s)
Lung Neoplasms , RNA, Circular , Biomarkers/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , RNA/genetics , RNA, Circular/genetics , ROC Curve , Real-Time Polymerase Chain ReactionABSTRACT
Circular RNAs (circ RNAs) have been found to play an important role in cancer development. However, the role of circRAB3IP in osteosarcoma (OS) is unclear.In the present study, We found that circRAB3IP was highly expressed in OS tissues and OS cells. High levels of circRAB3IP was correlated with advanced TNM stage, distant metastasis. CircRAB3IP knockdown inhibited cell proliferation, migration, and invasion. Moreover, circRAB3IP directly binds to miR-580-3p. TWIST1 is directly targeted by miR-580-3p. We also demonstrated that circRAB3IP act as the sponge of miR-580-3p to promote TWIST1 expression. CircRAB3IP promotes OS cells proliferation, migration, and invasion through modulating miR-580-3p/TWIST1 axis. Moreover, circRAB3IP facilitated tumor formation in vivo. Our findings suggested that circRAB3IP acts as an oncogene in OS by regulating miR-580-3p/TWIST1 axis.
Subject(s)
Bone Neoplasms , MicroRNAs/genetics , Nuclear Proteins/genetics , Osteosarcoma , RNA, Circular/genetics , Twist-Related Protein 1/genetics , Adolescent , Adult , Animals , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Line, Tumor , Child , Disease Progression , Female , Humans , Male , Mice , Mice, Inbred BALB C , MicroRNAs/metabolism , Nuclear Proteins/metabolism , Osteosarcoma/genetics , Osteosarcoma/metabolism , Osteosarcoma/pathology , RNA, Circular/metabolism , Twist-Related Protein 1/metabolism , Young AdultABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is still a worldwide challenge. Accumulated evidence demonstrates that the superiority of immune-related long noncoding RNAs (lncRNAs) are closely connected with tumorigenesis and prognosis of cancer. However, no detailed studies have been conducted to present a reliable signature for predicting prognosis in LUAD patients from the perspective of tumor immunology. The aim of this study was to con-struct a risk score model based on the signature of the group of seven immune-related lncRNAs to predict the prognosis of patients with LUAD. METHODS: We performed a genome-wide analysis of expression profiles in 522 LUAD patients from The Cancer Genome Atlas (TCGA) project to explore the prognostic ability of immune-related lncRNAs. By using Kaplan-Meier analysis, univariate/multivariate Cox regression, receiver operating characteristic curve (ROC), and principal components analysis (PCA), a risk score model was constructed based on the signature of the group of seven immune-related lncRNAs to predict the prognosis of patients with LUAD. RESULTS: Using survival analysis and Cox regression model, we identified a set of seven lncRNAs (LINC00941, FAM83A-AS1, AC026355.1, AC068338.3, AC010980.2, AL365181.2, and AC079949.2) demonstrating an ability to stratify patients into high and low risk groups with significantly different survival outcomes. Moreover, the signature was identified as an independent prognostic factor and significantly associated with the overall survival (OS) of LUAD. The area under curve (AUC) of a ROC curve for the signature of the group of seven immune-related lncRNAs in predicting OS was 0.757. In addition, low-risk and high-risk groups displayed different immune statuses based on PCA. CONCLUSIONS: This study suggested a promising seven prognostic immune-related lncRNAs risk scoring system and may provide new information for immunological treatment in LUAD.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , RNA, Long Noncoding , Adenocarcinoma of Lung/genetics , Biomarkers, Tumor/genetics , Humans , Lung Neoplasms/genetics , Prognosis , RNA, Long Noncoding/genetics , RNA-SeqABSTRACT
The cancer/testis antigen lactate dehydrogenase-C4 (LDHC) is a specific isoenzyme of the LDH family that regulates invasion and metastasis in some malignancies; however, little is known regarding its role in progression of lung adenocarcinoma (LUAD). Thus, we investigated LDHC expression by immunohistochemistry, and analyzed its clinical significance in 88 LUAD specimens. The role and molecular mechanisms subserving LDHC in cellular proliferation, migration, and invasion were explored both in vitro and in vivo. As a result, we found that high LDHC expression was significantly correlated with clinicopathological features of aggressive LUAD and a poor prognosis. Overexpression of LDHC induced LUAD cells to produce lactate and ATP, increased their metastatic and invasive potential-, and accelerated xenograft tumor growth. We further demonstrated that overexpression of LDHC affected the expression of cell proliferation-related proteins (cyclin D1 and c-Myc) and epithelial-mesenchymal transition (EMT)-related proteins (MMP-2, MMP-9, E-cadherin, Vimentin, Twist, Slug, and Snail) both in vitro and in vivo. Finally, excessive activation of LDHC enhanced the phosphorylation levels of AKT and GSK-3ß, revealing activation of the PI3K/Akt/GSK-3ß oncogenic-signaling pathways. Treatment with a PI3K inhibitor reversed the effects of LDHC overexpression by inhibiting cellular proliferation, migration, and invasion, with diminished levels of p-Akt and p-GSK3ß. PI3K inhibition also reversed cell proliferation-related and EMT-related proteins in LDHC-overexpressing A549 cells. In conclusion, LDHC promotes proliferation, migration, invasion, and EMT in LUAD cells via activation of the PI3K/Akt/GSK-3ß pathway.