Computer-aided diagnosis system for optical diagnosis of colorectal polyps under white light imaging.

OBJECTIVES: This study presents a novel computer-aided diagnosis (CADx) designed for optically diagnosing colorectal polyps using white light imaging (WLI).We aimed to evaluate the effectiveness of the CADx and its auxiliary role among endoscopists with different levels of expertise. METHODS: We collected 2,324 neoplastic and 3,735 nonneoplastic polyp WLI images for model training, and 838 colorectal polyp images from 740 patients for model validation. We compared the diagnostic accuracy of the CADx with that of 15 endoscopists under WLI and narrow band imaging (NBI). The auxiliary benefits of CADx for endoscopists of different experience levels and for identifying different types of colorectal polyps was also evaluated. RESULTS: The CADx demonstrated an optical diagnostic accuracy of 84.49%, showing considerable superiority over all endoscopists, irrespective of whether WLI or NBI was used (P < 0.001). Assistance from the CADx significantly improved the diagnostic accuracy of the endoscopists from 68.84% to 77.49% (P = 0.001), with the most significant impact observed among novice endoscopists. Notably, novices using CADx-assisted WLI outperform junior and expert endoscopists without such assistance. CONCLUSIONS: The CADx demonstrated a crucial role in substantially enhancing the precision of optical diagnosis for colorectal polyps under WLI and showed the greatest auxiliary benefits for novice endoscopists.

Cellular and molecular mechanisms of oroxylin A in cancer therapy: Recent advances.

Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.

A D-cysteine desulfhydrase, SlDCD2, participates in tomato fruit ripening by modulating ROS homoeostasis and ethylene biosynthesis.

Hydrogen sulfide (H2S) is involved in multiple processes during plant growth and development. D-cysteine desulfhydrase (DCD) can produce H2S with D-cysteine as the substrate; however, the potential developmental roles of DCD have not been explored during the tomato lifecycle. In the present study, SlDCD2 showed increasing expression during fruit ripening. Compared with the control fruits, the silencing of SlDCD2 by pTRV2-SlDCD2 accelerated fruit ripening. A SlDCD2 gene-edited mutant was constructed by CRISPR/Cas9 transformation, and the mutant exhibited accelerated fruit ripening, decreased H2S release, higher total cysteine and ethylene contents, enhanced chlorophyll degradation and increased carotenoid accumulation. Additionally, the expression of multiple ripening-related genes, including NYC1, PAO, SGR1, PDS, PSY1, ACO1, ACS2, E4, CEL2, and EXP was enhanced during the dcd2 mutant tomato fruit ripening. Compared with the wild-type fruits, SlDCD2 mutation induced H2O2 and malondialdehyde (MDA) accumulation in fruits, which led to an imbalance in reactive oxygen species (ROS) metabolism. A correlation analysis indicated that H2O2 content was strongly positively correlated with carotenoids content, ethylene content and ripening-related gene expression and negatively correlated with the chlorophyll content. Additionally, the dcd2 mutant showed earlier leaf senescence, which may be due to disturbed ROS homeostasis. In short, our findings show that SlDCD2 is involved in H2S generation and that the reduction in endogenous H2S production in the dcd2 mutant causes accelerated fruit ripening and premature leaf senescence. Additionally, decreased H2S in the dcd2 mutant causes excessive H2O2 accumulation and increased ethylene release, suggesting a role of H2S and SlDCD2 in modulating ROS homeostasis and ethylene biosynthesis.

ß-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice.

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

Relative decline in serum albumin help to predict anastomotic leakage for female patients following sphincter-preserving rectal surgery.

BACKGROUND: Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. METHODS: Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. RESULTS: Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. CONCLUSIONS: The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

A Coculture of Enterobacter and Comamonas Species Reduces Cadmium Accumulation in Rice.

The accumulation of cadmium (Cd) in plants is strongly impacted by soil microbes, but its mechanism remains poorly understood. Here, we report the mechanism of reduced Cd accumulation in rice by coculture of Enterobacter and Comamonas species. In pot experiments, inoculation with the coculture decreased Cd content in rice grain and increased the amount of nonbioavailable Cd in Cd-spiked soils. Fluorescence in situ hybridization and scanning electron microscopy detection showed that the coculture colonized in the rhizosphere and rice root vascular tissue and intercellular space. Soil metagenomics data showed that the coculture increased the abundance of sulfate reduction and biofilm formation genes and related bacterial species. Moreover, the coculture increased the content of organic matter, available nitrogen, and potassium and increased the activities of arylsulfatase, ß-galactosidase, phenoloxidase, arylamidase, urease, dehydrogenase, and peroxidase in soils. In subsequent rice transcriptomics assays, we found that the inoculation with coculture activated a hypersensitive response, defense-related induction, and mitogen-activated protein kinase signaling pathway in rice. Heterologous protein expression in yeast confirmed the function of four Cd-binding proteins (HIP28-1, HIP28-4, BCP2, and CID8), a Cd efflux protein (BCP1), and three Cd uptake proteins (COPT4, NRAM5, and HKT6) in rice. Succinic acid and phenylalanine were subsequently proved to inhibit rice divalent Cd [Cd(II)] uptake and activate Cd(II) efflux in rice roots. Thus, we propose a model that the coculture protects rice against Cd stress via Cd immobilization in soils and reducing Cd uptake in rice. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

[Proteomics analysis of Astragalus polysaccharide on TLR4-activated lung cancer cell-derived exosomes].

Astragalus polysaccharide(APS), one of the main active components of Astragali Radix, plays an anti-tumor effect by regulating the inflammatory microenvironment of tumors. Exosomes are small extracellular vesicles with a diameter ranging from 50 to 200 nm and carry several biological components from parental cells such as nucleic acids and proteins. When combined with recipient cells, they play an important role in intercellular communication and immune response. In this study, exosomes released from H460 cells at the inflammatory state or with APS addition activated by Toll-like receptor 4(TLR4) were extracted by ultracentrifugation and characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. The exosomal proteins derived from H460 cells in the three groups were further analyzed by label-free proteomics, and 897, 800, and 911 proteins were identified in the three groups(Con, LPS, and APS groups), 88% of which belonged to the ExoCarta exosome protein database. Difference statistical analysis showed that the expression of 111 proteins was changed in the LPS group and the APS group(P<0.05). The biological information analysis of the differential proteins was carried out. The molecular functions, biological processes, and signaling pathways related to the differential proteins mainly involved viral processes, protein binding, and bacterial invasion of proteasome and epithelial cells. Key differential proteins mainly included plasminogen activator inhibitor-1, laminin α5, laminin α1, and CD44, indicating that tumor cells underwent systemic changes in different states and were reflected in exosomes in the inflammatory microenvironment. The analysis results also suggested that APS might affect the inflammatory microenvironment through the TLR4/MyD88/NF-κB signaling pathway or the regulation of the extracellular matrix. This study is conducive to a better understanding of the mechanism of tumor development in the inflammatory state and the exploration of the anti-inflammatory effect of APS at the exosome level.

Roles of Krüppel-like factor 6 splice variant 1 in the development, diagnosis, and possible treatment strategies for non-small cell lung cancer.

Krüppel-like factor 6 (KLF6) is a nuclear transcriptional regulator found in mammalian tissue that has been identified as a tumor suppressor gene in several malignancies. As a result of loss of heterozygosity, DNA methylation, and alternative splicing, it is frequently inactivated in various malignancies. Krüppel-like factor 6 splice variant 1 (KLF6-SV1), Krüppel-like factor 6 splice variant 2, and Krüppel-like factor 6 splice variant 3 alternatively spliced isoforms that emerge from a single nucleotide polymorphism in the KLF6 gene. KLF6-SV1 is generally upregulated in multiple cancers, and its biological function is well understood. Overexpression of KLF6-SV1 inhibits the KLF6 gene function while promoting tumor progression, which is associated with a poor prognosis in patients with various malignancies. We reviewed the progress of KLF6-SV1 research in NSCLC over the last several years to understand the molecular mechanisms of tumorigenesis, tumor development, and therapy resistance. Finally, this review emphasizes the therapeutic potential of small interfering RNA targeted silencing of KLF6-SV1 as a novel strategy for managing chemotherapy resistance in NSCLC patients.

A Hydrogen-Sulfide-Repressed Methionine Synthase SlMS1 Acts as a Positive Regulator for Fruit Ripening in Tomato.

Ethylene is a key phytohormone that regulates the ripening of climacteric fruits, and methionine is an indirect precursor of ethylene. However, whether methionine synthase plays a role in fruit ripening in Solanum lycopersicum (tomato) is still unknown. In this study, we find that a tomato methionine synthase (named SlMS1), which could be repressed at the transcriptional level by hydrogen sulfide (H2S), acts as a positive regulator for tomato fruit ripening. By a bioinformatics analysis, it is found that SlMS1 and SlMS2 in tomato are highly homologous to methionine synthases in Arabidopsis thaliana. The expression pattern of SlMS1 and SlMS2 is analyzed in tomato, and SlMS1 expression is up-regulated during fruit ripening, suggesting its potential role in regulating fruit ripening. A potential bipartite nuclear localization signal is found in the amino acid sequence of SlMS1; thus, SlMS1 is tagged with GFP and observed in the leaves of Nicotiana benthamiana. Consistently, SlMS1-GFP shows strong nuclear localization and also cytoplasmic localization. The role of SlMS1 in regulating fruit ripening is investigated in tomato fruit by transient silencing (virus-induced gene silencing, VIGS) and transient overexpression. The results show that SlMS1 silencing causes delayed fruit ripening, evidenced by more chlorophyll and less carotenoid accumulation, while SlMS1 overexpression accelerates fruit ripening significantly compared with control. Further investigation shows that SlMS1 overexpression could up-regulate the expression of carotenoid-synthesis-related genes (PSY1, PDS, ZDS), chlorophyll-degradation-related genes (NYC1, PAO, PPH, SGR1), cell-wall-metabolism-related genes (CEL2, EXP, PG, TBG4, XTH5) and ethylene-synthesis-pathway-related genes (ACO1, ACO3, ACS2), while SlMS1 silencing causes the opposite results. The correlation analysis indicates that SlMS1 expression is negatively correlated with chlorophyll content and positively correlated with carotenoid and ripening-related gene expressions. Taken together, our data suggest that SlMS1 is a positive regulator of tomato fruit ripening and a possible target gene for the ripening-delaying effect of H2S.

The impact of postoperative complications severity on stoma reversal following sphincter-preserving surgery for rectal cancer.

BACKGROUND: Currently, the relationship between temporary stoma reversal and the severity of postoperative complications (POCs) after the index surgery based on the Clavien-Dindo classification has not yet been explored. METHODS: From July 2010 to June 2016, 380 patients undergoing sphincter-preserving surgery for rectal cancer with a temporary stoma in our hospital were included. Temporary stoma nonclosure rates, disease-free survival rates, and overall survival rates were estimated utilizing the Kaplan-Meier method. RESULTS: Of all the 380 patients, primary stomas were created in 335 patients and secondary stomas in 45 patients. After the index surgery, 36.6% (139/380) of patients developed at least one postoperative complication. In the first analysis, which included all the patients, 24.7% of temporary stomas remained unclosed. In the second analysis for 335 patients with a primary stoma, 23.3% were left with unclosed stomas. After the COX regression analysis, both major POCs and minor POCs were found to be independent risk factors for the permanent stoma, and there was an increasing tendency toward the risk of permanent stoma with the increase in POC severity. CONCLUSION: POCs are independent predictors of permanent stoma after rectal cancer surgery. Even minor POCs may affect the outcome, while there is a clear direct relationship between POC severity and permanent stoma rates.

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review).

Esophageal cancer (EC) is the seventh most common cancer globally, and the overall 5­year survival rate is only 20%. Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in EC, and its activation is associated with a poor prognosis. STAT3 can be activated by canonical pathways such as the JAK/STAT3 pathway as well as non­canonical pathways including the Wnt/STAT3 and COX2/PGE2/STAT3 pathways. Activated STAT3, present as phosphorylated STAT3 (p­STAT3), can be transported into the nucleus to regulate downstream genes, including VEGF, cyclin D1, Bcl­xL, and matrix metalloproteinases (MMPs), to promote cancer cell proliferation and induce resistance to therapy. Non­coding RNAs, including microRNAs (miRNAs/miRs), circular RNAs (circRNAs), and long non­coding RNAs (lncRNAs), play a vital role in regulating the STAT3 signaling pathway in EC. Several miRNAs promote or suppress the function of STAT3 in EC, while lncRNAs and circRNAs primarily promote the effects of STAT3 and the progression of cancer. Additionally, various drugs and natural compounds can target STAT3 to suppress the malignant behavior of EC cells, providing novel insights into potential EC therapies.

Comparison of the BOPPPS model and traditional instructional approaches in thoracic surgery education.

BACKGROUND: BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) is a student-centered modular teaching model that improves classroom teaching effectiveness. This study's primary aim was to explore whether the BOPPPS model has advantages over traditional instructional approaches in teaching lung cancer courses to clinical medical interns. METHODS: A total of 88 students majoring in clinical medicine of Shandong First Medical University and Shandong University, who had clinical practice in thoracic surgery from January 2018 to December 2019, were divided into two groups, receiving the same lung cancer teaching content. The experimental group (n = 44) utilized the BOPPPS model, while the control group (n = 44) used the traditional instructional approach. A questionnaire was used to attain the students' satisfaction and self-evaluation of the course, and a post-study examination was used to assess end-of-course performance. RESULTS: The experimental group's theoretical examination scores with the BOPPPS teaching model were significantly higher than those in the control group. Students preferred the BOPPPS model more than the traditional instructional approach in course satisfaction, student-teacher interaction, learning initiative, analytical ability, clinical thinking ability, and self-study ability (p < 0.05). CONCLUSIONS: Compared with the traditional instructional approach. The BOPPPS model can better inspire clinical medical students' enthusiasm for thoracic surgery and enhance the students' comprehensive ability. In a word, the BOPPPS model has better teaching effectiveness in the clinical teaching practice of thoracic surgery, which is worthy of reference and popularization.

Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.

According to the latest statistics from the International Agency for Research on Cancer (IARC), lung cancer is one of the most lethal malignancies in the world, accounting for approximately 18% of all cancer-associated deaths. Yet, even with aggressive interventions for advanced lung cancer, the five-year survival rate remains low, at around 15%. The hedgehog signaling pathway is highly conserved during embryonic development and is involved in tissue homeostasis as well as organ development. However, studies have documented an increasing prevalence of aberrant activation of HH signaling in lung cancer patients, promoting malignant lung cancer progression with poor prognostic outcomes. Inhibitors targeting the HH pathway have been widely used in tumor therapy, however, they still cannot avoid the occurrence of drug resistance. Interestingly, natural products, either alone or in combination with chemotherapy, have greatly improved overall survival outcomes for lung cancer patients by acting on the HH signaling pathway because of its unique and excellent pharmacological properties. In this review, we elucidate on the underlying molecular mechanisms through which the HH pathway promotes malignant biological behaviors in lung cancer, as well as the potential of inhibitors or natural compounds in targeting HH signaling for clinical applications in lung cancer therapy.

Oak-inspired anti-biofouling shape-memory unidirectional scaffolds with stable solar water evaporation performance.

Biomimetic porous materials have contributed to the enhancement of solar-driven evaporation rate in interfacial desalination and clean water production. However, due to the presence of numerous microbes in water environment, biofouling should occur inside porous materials to clog the channels for water transfer, resulting in obvious inhibition of the solar-driven evaporation efficacy in long-term use. To prevent and control biofouling in porous materials for solar-driven evaporation, a facile and environment-friendly design is required in real application. Oak wood possesses vertically aligned channels for transpiration and polyphenol compounds with antimicrobial activity. In this work, inspired by the oak wood, we developed an anti-biofouling shape-memory chitosan scaffold with unidirectional channels and tannic acid coating (oak-inspired scaffold). The shape-memory property facilitated rapid decoration with oak-inspired photothermal and anti-biofouling coating inside the scaffold, respectively, which also promotes the material durability by avoiding the external force-induced permanent structure failure. More importantly, the oak-inspired tannic acid coating not only prevented bacterial adhesion and colonization, but also inhibited fungal interference. They were subjected to a microbe-rich environment, and after 3 days, the evaporation rates of the untreated chitosan scaffolds were obviously decreased to 1.24, 1.16 and 1.19 kg m-2 h-1 for C. albicans, S. aureus and E. coli, respectively, which were only 65.6, 61.4 and 63.0% of original performance (1.89 kg m-2 h-1). In comparison, the oak-inspired scaffold exhibited a high solar-driven water evaporation rate after incubation in microbial suspensions (1.80, 1.70 and 1.75 kg m-2 h-1 for C. albicans, S. aureus and E. coli after 3 days) and lake water (1.74 kg m-2 h-1 after one month). The bioinspired anti-biofouling scaffolds maintain as high as 86.7-91.8% of the solar-driven water evaporation ability after exposure to a microbe-rich environment, which is conducive to develop a biomimetic long-term durable structure in water treatment.

Contrasting resistance of polycyclic aromatic hydrocarbons to atmospheric oxidation influenced by burning conditions.

The oxidation of polycyclic aromatic hydrocarbons (PAHs) determines their lifetime, toxicity and consequent environmental and climate impacts. The residential solid fuel burning composes of a substantial fraction of PAH emissions; however, their oxidation rate is yet to be explicitly understood, which is complicated by the contrasting emission factors under different combustion conditions and their subsequent evolution in the atmosphere. Here we used a plume evolution chamber using ambient oxidants to simulate the evolution of residential solid fuel burning emissions under real-world solar radiation, and then to investigate the oxidation process of the emitted PAHs. Contrasting oxidation rate of PAHs was found to be influenced by particles with or without presence of substantial amount of black carbon (BC). In the flaming burning phase, which contained 46% of BC mass fraction and 8% of organic aerosol (OA) internally mixed with BC, the larger PAHs (with 4-7 rings) was rapidly oxidized 12% for every hour of evolution under solar radiation; however, the larger PAHs from smoldering phase tended to maintain unmodified during the evolution, when 95% of OA was externally mixed with only minor fraction of BC (<5%). This may be ascribed to the complex morphology of BC, allowing more exposure for the internally-mixed OA to the oxidants; in contrast with those externally-mixed OA which was prone to be coated by condensed secondary substances. This raises an important consideration about the particle mixing state in influencing the oxidation of PAHs, particularly the coating on PAHs which may extend their lifetime and environmental impacts.

The molecular mechanism of METTL3 promoting the malignant progression of lung cancer.

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.

ADAMTS8 inhibited lung cancer progression through suppressing VEGFA.

BACKGROUND: ADAMTS8 expression has been identified to be low in many cancers including lung cancer. However, the specific functions and regulatory system of ADAMTS8 remain to be unveiled. PURPOSE: To study the potential modulatory mechanism of ADAMTS8 in lung cancer in cell and xenograft mice models. METHODS: Differential expression of ADAMTS8 in lung cancer was analyzed on online tools. So was the overall survival curve in association with ADAMTS8/VEGFA expression in lung cancer patients. RT-qPCR was applied to validate the ADAMTS8 expression in lung cancer cell lines H460 and A549, with the normal lung epithelial cell Beas-2b as a control. Thereafter, overexpressed and knockdown plasmids were constructed for transfection. Colony and flow cytometry methods were used for cell proliferation and apoptosis. RT-qPCR and Western blot methods validated the changes in VEGFA after ADAMTS8 regulation in cells. Tube formation and Transwell methods were applied to observe the changes in tube formation and migration in HUVECs induced by tumor conditioned medium (TCM). Stable-transfected cells were injected subcutaneously into nude mice. H&E and Immunohistochemistry were applied to analyze the pathological differences and protein changes of ADAMTS8, VEGFA and CD31. RESULTS: High ADAMTS8 was correlated with high overall survival rate in lung cancer patients. ADAMTS8 was also abnormally downregulated in NSCLC cells. Upregulation of ADAMTS8 suppressed cell proliferation and enhanced apoptosis while downregulation of ADAMTS8 promoted cell proliferation and decreased apoptosis. VEGFA was negatively correlated with ADAMTS8 in lung cancer tissues. Upregulation of ADAMTS8 inhibited VEGFA in mRNA and protein levels. Further, knockdown of ADAMTS8 induced tube formation and migration of HUVECs and upregulation of ADAMTS8 inhibited this. In addition, upregulation of ADAMTS8 in nude mice inhibited tumor growth and also suppressed VEGFA and CD31 in tumors. CONCLUSION: ADAMTS8 inhibited lung cancer progression through suppressing VEGFA in lung cancer.