Research Progress on CARM1 and its Relationship with Colorectal Cancer.

Coactivator-associated arginine methyltransferase 1 (CARM1) is significant as a key member of the PRMT family, crucial for regulating arginine methylation, and its association with colorectal cancer underscores its potential as a therapeutic target. Consequently, CARM1 inhibitors have emerged as potential therapeutic agents in cancer treatment and valuable chemical tools for cancer research. Despite steady progress in CARM1 inhibitor research, challenges persist in discovering effective, isoform-selective, cell-permeable, and in vivo-active CARM1 inhibitors for colorectal cancer. This review summarizes the research progress on CARM1 and its relationship with colorectal cancer, aiming to provide a theoretical basis for the radiotherapy of colorectal cancer.

BioCaster in 2021: automatic disease outbreaks detection from global news media.

SUMMARY: BioCaster was launched in 2008 to provide an ontology-based text mining system for early disease detection from open news sources. Following a 6-year break, we have re-launched the system in 2021. Our goal is to systematically upgrade the methodology using state-of-the-art neural network language models, whilst retaining the original benefits that the system provided in terms of logical reasoning and automated early detection of infectious disease outbreaks. Here, we present recent extensions such as neural machine translation in 10 languages, neural classification of disease outbreak reports and a new cloud-based visualization dashboard. Furthermore, we discuss our vision for further improvements, including combining risk assessment with event semantics and assessing the risk of outbreaks with multi-granularity. We hope that these efforts will benefit the global public health community. AVAILABILITY AND IMPLEMENTATION: BioCaster web-portal is freely accessible at http://biocaster.org.

KLK5 is associated with the radioresistance, aggression, and progression of cervical cancer.

OBJECTIVE: The role of kallikrein-related peptidase 5 (KLK5) has been studied in several diseases, including skin and ovarian cancers. However, its role in cervical cancer remains unclear, particularly in regulating the radiation resistance and growth of cervical cancer cells. Radiation resistance of cervical cancer is associated with local recurrence, distant metastasis, and reduced survival. METHODS: We first analyzed radiotherapy-naive samples and relevant clinical data from patients with cervical cancer who received radiotherapy without surgery or other antitumor treatment from 2014 to 2016. Subsequently, biopsied tissues, in vitro cells, and transplanted tumors in nude mice were investigated. RESULTS: Gene sequencing and clinical data analysis showed that KLK5 overexpression was associated with a poor prognosis post-radiotherapy. In in vitro cell and tumor transplantation experiments, KLK5 overexpression significantly increased radiation resistance. However, downregulating KLK5 expression increased radiosensitivity. CONCLUSION: Our results confirm that KLK5 is vital to the radioresistance of cervical cancer, and provide a new target and marker for the treatment of radioresistance in cervical cancer.

Matrix stiffness regulates macrophage polarization in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease and the pathological basis of many fatal cardiovascular diseases. Macrophages, the main inflammatory cells in atherosclerotic plaque, have a paradox role in disease progression. In response to different microenvironments, macrophages mainly have two polarized directions: pro-inflammatory macrophages and anti-inflammatory macrophages. More and more evidence shows that macrophage is mechanosensitive and matrix stiffness regulate macrophage phenotypes in atherosclerosis. However, the molecular mechanism of matrix stiffness regulating macrophage polarization still lacks in-depth research, which hinders the development of new anti-atherosclerotic therapies. In this review, we discuss the important role of matrix stiffness in regulating macrophage polarization through mechanical signal transduction (Hippo, Piezo, cytoskeleton, and integrin) and epigenetic mechanisms (miRNA, DNA methylation, and histone). We hope to provide a new perspective for atherosclerosis therapy by targeting matrix stiffness and macrophage polarization.

Substantial increase in detection efficiency for filter array-based spectral sensors.

A method that significantly increases the detection efficiency of filter array-based spectral sensors is proposed. The basic concept involves a wavelength-dependent redistribution of incident light before it reaches the filter elements located in front of the detector. Due to this redistribution, each filter element of the array receives a spatially concentrated amount of a pre-selected and adjusted spectral partition of the entire incident light. This approach can be employed to significantly reduce the reflection and absorption losses of each filter element. The proof-of-concept is demonstrated by a setup that combines a series of consecutively arranged dichroic filters with Fabry-Perot filter arrays. Experimentally, an efficiency increase by a factor larger than 4 compared to a reference system is demonstrated. The optical system is a non-imaging spectrometer, which combines the efficiency enhancement module with the filter arrays, is compact (17.5mm×17.5mm×7.8mm), and integrated completely inside the CCD camera mount.

Effects and potential mechanisms of IGF1/IGF1R in the liver fibrosis: A review.

Liver fibrosis is a wound-healing response due to persistent liver damage and it may progress to cirrhosis and even liver cancer if no intervention is given. In the current cognition, liver fibrosis is reversible. So, it is of great significance to explore the related gene targets or biomarker for anti-fibrosis of liver. Insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R) are mainly expressed in the liver tissues and play critical roles in the liver function. The present review summarized the role of IGF1/IGF1R and its signaling system in liver fibrosis and illustrated the potential mechanisms including DNA damage repair, cell senescence, lipid metabolism and oxidative stress that may be involved in this process according to the studies on the fibrosis of liver or other organs. In particular, the roles of IGF1 and IGF1R in DNA damage repair were elaborated, including membrane-localized and nucleus-localized IGF1R. In addition, for each of the potential mechanism in anti-fibrosis of liver, the signaling pathways of the IGF1/IGF1R mediated and the cell species in liver acted by IGF1 and IGF1R under different conditions were included. The data in this review will support for the study about the effect of IGF1/IGF1R on liver fibrosis induced by various factors, meanwhile, provide a basis for the study of liver fibrosis to focus on the communications between the different kinds of liver cells.

One Stone, Three Birds: Multifunctional Nanodots as "Pilot Light" for Guiding Surgery, Enhanced Radiotherapy, and Brachytherapy of Tumors.

Surgery, radiotherapy (RT), and brachytherapy are crucial treatments for localized deep tumors. However, imprecise tumor location often leads to issues such as positive surgical margins, extended radiotherapy target volumes, and radiation damage to healthy tissues. Reducing side effects in healthy tissue and enhancing RT efficacy are critical challenges. To address these issues, we developed a multifunctional theranostic platform using Au/Ag nanodots (Au/AgNDs) that act as a "pilot light" for real-time guided surgery, high-efficiency RT, and brachytherapy, achieving a strategy of killing three birds with one stone. First, dual-mode imaging of Au/AgNDs enabled precision RT, minimizing damage to adjacent normal tissue during X-ray irradiation. Au/AgNDs enhanced ionizing radiation energy deposition, increased intracellular reactive oxygen species (ROS) generation, regulated the cell cycle, promoted DNA damage formation, and inhibited DNA repair in tumor cells, significantly improving RT efficacy. Second, in brachytherapy, precise guidance provided by dual-mode imaging addressed challenges related to non-visualization of existing interstitial brachytherapy and multiple adjustments of insertion needle positions. Meanwhile, the effect of brachytherapy was improved. Third, the excellent fluorescence imaging of Au/AgNDs accurately distinguished tumors from normal tissue, facilitating their use as a powerful tool for assisting surgeons during tumor resection. Taken together, our multifunctional theranostic platform offers real-time guidance for surgery and high-efficiency RT, and improves brachytherapy precision, providing a novel strategy and vision for the clinical diagnosis and treatment of cancer.

SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: implications for cell survival after irradiation.

Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggered nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.

A Conceptual Framework for Representing Events Under Public Health Surveillance.

Information integration across multiple event-based surveillance (EBS) systems has been shown to improve global disease surveillance in experimental settings. In practice, however, integration does not occur due to the lack of a common conceptual framework for encoding data within EBS systems. We aim to address this gap by proposing a candidate conceptual framework for representing events and related concepts in the domain of public health surveillance.

GATA3 Exerts Distinct Transcriptional Functions to Regulate Radiation Resistance in A549 and H1299 Cells.

Background: Radiation resistance of lung cancer cells is a vital factor affecting the curative effect of lung cancer. Transcription factor GATA3 is involved in cell proliferation, invasion, and migration and is significantly expressed in a variety of malignancies. However, the molecular mechanism governing GATA3 regulation in lung cancer cells' radiation resistance is unknown. Methods: Radiation-resistant cell models (A549-RR and H1299-RR) were made using fractionated high-dose irradiation. Use clone formation, CCK-8, F-actin staining, cell cycle detection, and other experiments to verify whether the model is successfully constructed. Cells were transiently transfected with knockdown or overexpression plasmid. To explore the relationship between GATA3/H3K4me3 and target genes, we used ChIP-qPCR, ChIP-seq, and dual luciferase reporter gene experiments. Xenograft tumor models were used to evaluate the effect of GATA3 depletion on the tumorigenic behavior of lung cancer cells. Results: We report that transcription factors GATA3 and H3K4me3 coactivate NRP1 gene transcription when A549 cells develop radiation resistance. However, the mechanism of radiation resistance in H1299 cells is that GATA3 acts as a transcription inhibitor. The decrease of GATA3 will promote the increase of NRP1 transcription, in which H3K4me3 does not play a leading role. Conclusions: GATA3, an upstream transcriptional regulator of NRP1 gene, regulates the radioresistance of A549 and H1299 cells by opposite mechanisms, which provides a new target for radiotherapy of lung cancer.

Analysis of risk factors for mental health problems of inpatients with chronic liver disease and nursing strategies: A single center descriptive study.

The number of patients with chronic liver disease (CLD) is large. The social and economic burdens due to CLD have increased. The mental health problems of patients with CLD are prominent and deserve our attention and care. This study analyzed 320 patients with CLD who were hospitalized between January 2018 and January 2020. Questionnaire surveys were used to assess mental health status, including the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Symptom Checklist-90 (SCL-90). At the same time, basic data and potential related factors were collected. Data were analyzed using descriptive statistics and logistic regression. Among the 320 patients with CLD, 240 (75%) had mental health problems; among the total patients, education levels, occupations, course of disease, annual hospitalizations, complications, and nursing satisfaction were significantly different between the two groups (p < .05). The education levels and occupations of the group without mental health problems were significantly different within the group (p < .05). The SCL-90 found that the four factors with the highest scores were anxiety (ANX: 33.3%), depression (DEPR: 20.4%), somatization (SOM: 12.9%), and sleep and diet (SD: 9.6%). Logistic regression analysis showed that education levels, course of disease, annual hospitalizations, complications, and nursing satisfaction levels were independent risk factors for the mental health of patients with CLD. Model fitness was checked using the Hosmer-Lemeshow test. The receiver operating characteristic (ROC) curve showed that the area under the curve was 0.84. Patients with CLD have prominent mental health problems and experience many risk factors. It is necessary to adopt individualized psychological interventions and care to improve the quality of life of these patients.

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers.

Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

Erratum: MicroRNA-26b suppresses autophagy in breast cancer cells by targeting DRAM1 mRNA, and is downregulated by irradiation.

[This corrects the article DOI: 10.3892/ol.2017.7452.].

The role of case importation in explaining differences in early SARS-CoV-2 transmission dynamics in Canada-A mathematical modeling study of surveillance data.

OBJECTIVE: The North American coronavirus disease-2019 (COVID-19) epidemic exhibited distinct early trajectories. In Canada, Quebec had the highest COVID-19 burden and its earlier March school break, taking place two weeks before those in other provinces, could have shaped early transmission dynamics. METHODS: We combined a semi-mechanistic model of SARS-CoV-2 transmission with detailed surveillance data from Quebec and Ontario (initially accounting for 85% of Canadian cases) to explore the impact of case importation and timing of control measures on cumulative hospitalizations. RESULTS: A total of 1544 and 1150 cases among returning travelers were laboratory-confirmed in Quebec and Ontario, respectively (symptoms onset ≤03-25-2020). Hospitalizations could have been reduced by 55% (95% CrI: 51%-59%) if no cases had been imported after Quebec's March break. However, if Quebec had experienced Ontario's number of introductions, hospitalizations would have only been reduced by 12% (95% CrI: 8%-16%). Early public health measures mitigated the epidemic spread as a one-week delay could have resulted in twice as many hospitalizations (95% CrI: 1.7-2.1). CONCLUSION: Beyond introductions, factors such as public health preparedness, responses and capacity could play a role in explaining interprovincial differences. In a context where regions are considering lifting travel restrictions, coordinated strategies and proactive measures are to be considered.

Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial.

OBJECTIVES: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS. METHODS: This was a double-blind, randomized, multicountry, placebo-controlled, parallel-group trial enrolling patients ≥18 years old with confirmed EPI due to CP or PS conducted in clinical research centers or hospitals. After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100 g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period, analyzed using non-parametric analysis of covariance. Secondary outcomes included the coefficient of nitrogen absorption (CNA), clinical symptoms, and safety parameters. RESULTS: In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected]. Similarly, the mean ± s.d. change from baseline in CNA was greater for pancrelipase vs. placebo: 35.2 ± 29.1 vs. 8.9 ± 28.0 % ( P = 0.0005) [corrected].Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders. There were no treatment discontinuations due to TEAEs. CONCLUSIONS: Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.

NRP1 regulates radiation-induced EMT via TGF-ß/Smad signaling in lung adenocarcinoma cells.

PURPOSE: Radiation has been shown to promote the epithelial-mesenchymal transition (EMT) in tumor cells, and TGF-ß/Smad and PI3K-Akt signaling pathways play an important role in the EMT. In this study, we investigated the effects of neuropilin-1 (NRP1) on radiation-induced TGF-ß/Smad and non-classical Smad signaling pathways in lung cancer cells, as well as the effects of NRP1 on invasion and migration. MATERIALS AND METHODS: Changes in the expression levels of EMT markers (ß-catenin, N-cadherin, and vimentin) and related transcription factors (Twist and ZEB1) in stably transfected cells were detected by Western blotting and qPCR, and changes were assessed by TGF-ß/Smad and non-classical Smad signaling. Immunofluorescence was used to detect the expression of the cytoskeletal protein F-actin. Expression of TGF-ß1 and CXCL-12 was detected by ELISA. Transwell and scratch assays were used to detect the invasive ability and migration of lung cancer cells, respectively. RESULTS: Our results showed that ionizing radiation could induce the EMT as well as morphological changes in lung adenocarcinoma cells (A549); however, the effects were not significant in lung squamous carcinoma cells (SK-MES-1). Moreover, we showed that NRP1 promotes the EMT induced by ionizing radiation in A549 cells, which may be related to the increased expression of EMT-related transcription factors. NRP1 may promote the radiation-induced EMT of A549 cells mainly through TGF-ß1/Smad2/3 signaling. NRP1 also enhanced radiation-induced invasion, migration, and CXCL-12 expression in A549 cells. CONCLUSIONS: We conclude that NRP1 promotes radiation-induced EMT in lung adenocarcinoma cells via TGF-ß1/Smad signaling and not non-classical Smad signaling, and enhances the invasion and migration of lung adenocarcinoma cells.

The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells.

Background: Neuropilin 1 (NRP1) is a pleiotropic receptor which can interact with multiple ligands and their receptors. It plays an important role in the process of axonal growth, angiogenesis, tumor metastasis and radiation resistance in endothelial cells and some tumor cells. Interaction of stromal and tumor cells plays a dynamic role in initiating and enhancing carcinogenesis, and has received considerable attention in recent years. Material and Methods: In this study, A549 lung cancer cell lines with different NRP1 expression levels were constructed in vitro, a two-dimensional (2D), three-dimensional (3D) co-culture system and tumor-bearing model was established in SCID mice. Western blot, qRT-PCR, immunofluorescence, cytometric bead array and flow cytometry were used to investigate the effect of the tumor microenvironment in NRP1-induced lung cancer cell radiation resistance. Results: In 2D or 3D co-culture system, NRP1 could be regulated inflammatory factors such as TNF, IL-6 IL-8 and IL-17 and the related chemokines MCP-1, IP-10 and RANTES in the tumor microenvironment, which in turn induced radiation resistance in lung cancer cells. In addition, different expression levels of NRP1 in 2D, 3D culture systems and tumor-bearing models were able to significantly regulate cell phenotype, proliferative capacity, epithelial-mesenchymal transition (EMT) and the radiation resistance of A549 cells. Conclusion: Our results verified that NRP1, inflammatory factors, chemokines and related signaling pathways, which affect the transformation of related cell components and thus lung cancer cell immune tolerance and migratory ability, all play an important role in radiation resistance.

MicroRNA-9 enhanced radiosensitivity and its mechanism of DNA methylation in non-small cell lung cancer.

In order to improve the therapeutic effect of non-small cell lung cancer (NSCLC), it is critical to combine radiation and gene therapy. Our study found that the activation of microRNA-9 (miR-9) conferred ionizing radiation (IR) sensitivity in cancer cells. Furthermore, increased microRNA-9 promoter methylation level was observed after IR. Our study combined the IR and microRNA-9 overexpression treatment which leads to a significant enhancement in the therapeutic efficiency in lung cancer both in vitro and in vivo. Therefore, it is plausible that microRNA-9 can be used as a novel therapeutic strategy of NSCLC. MTT assay was performed to detect the effect of microRNA-9 on the survival and growth of NSCLC cells. Flow cytometry results showed that microRNA-9 enhanced the apoptosis of NSCLC cells. Wound healing assay found that microRNA-9 can inhibit the migration of NSCLC cells and enhance the effect of radiation on the migration of NSCLC cells. In addition, bisulfate sequencing PCR was performed to analyze the methylation status of the microRNA-9 promoter. In order to determine the effect of microRNA-9 and its promoter methylation status on proliferation and radio-sensitivity in vivo, a subcutaneous tumor formation assay in nude mice was performed. Results have shown that microRNA-9 overexpression increased the radiosensitivity of A549 cells by inhibiting cell activity and migration, and by increasing apoptosis. In addition, the promoter methylation status of the microRNA-9 gene increased in response to ionizing radiation. Our study demonstrated that microRNA-9 enhanced radiosensitivity in NSCLC and this effect is highly regulated by its promoter methylation status. These results will help to clarify regulatory mechanisms of radiation resistance thus stimulate new methods for improving radiotherapy for NSCLC.

MicroRNA-26b suppresses autophagy in breast cancer cells by targeting DRAM1 mRNA, and is downregulated by irradiation.

MicroRNAs (miRs) are small RNAs that do not code for proteins, but instead decrease the stability and suppress the translation of target mRNAs by binding with complementary sequences in their 3'-untranslated regions (3'-UTRs). In the present study, it is reported that breast cancer tumor tissue, as well as irradiated MCF7 breast cancer cells, exhibit decreased levels of miR-26b expression compared with normal breast tissue and MCF7 cells without exposure to radiation. Additionally, a luciferase reporter assay was used to demonstrate that miR-26b directly targetsDNA damage-regulated autophagy modulator 1 (DRAM1). MCF7 cells that were transfected with an miR-26b mimicexhibited the downregulated expression of DRAM1 protein and a reduced level of irradiation-induced autophagy. Inhibiting miR-26b resulted in the upregulation of DRAM1 and increased levels of irradiation-induced autophagy in MCF7 cells. These results suggest that therapeutic strategies to target miR-26b may increase the efficacy of certain types of cancer therapy.

Mechanism of MEN1 gene in radiation-induced pulmonary fibrosis in mice.

OBJECTIVE: To investigate the regulatory mechanism of MEN1 gene in radiation-induced lung fibrosis in mice and provide a new theoretical basis for the clinical treatment of radiation pulmonary fibrosis. METHODS: First, 80 C57BL/6 mice aged 8 weeks and weighing 18-22 g were selected, half of them were male and the other half were female. The mice were divided into control group and irradiation group (40 mice in each group) according to the method of the random number table. A radiation-induced lung fibrosis mouse model was established in which a single X-ray irradiation of 20 Gy was applied to the right lung in the irradiation group; H&E and Masson staining were used to verify whether the model was successful at 4, 8, 16 and 24 weeks after irradiation. The expression of MEN1, smooth muscle actin (α-SMA), Collagen-1 and transforming growth factor (TGF-ß) in lung tissue were detected by Western blot and qPCR. Secondly, in the mouse embryonic fibroblast cell line (MEF) and mouse lung epithelial cell line (MLE-12), we constructed cell models of MEN1 knockout and interference separately with the irradiation of 10 Gy X-rays. The expression of α-SMA, Collagen-1, and TGF-ß/Smads signaling pathway molecules was detected by qPCR. Finally, using the immunoprecipitation (IP) method, we can detect the interaction between Smad2 and the protein menin encoded by the MEN1 gene. RESULTS: The results of the radiation pulmonary fibrosis model in mice showed that compared with the control group, the alveolar septum widens, the alveolar integrity decreases, the lung tissue slightly thickens, and a small amount of collagen deposits appear after 4-8 weeks in the model group. At twenty-fourth weeks, a large number of cells in the interstitial space of the lung tissue and a localized focal fibrosis area were observed. Further study found that radiation induced fibrogenic inflammatory cytokines TGF-ß up-regulation, down-regulation of MEN1 gene expression, and then enhanced the expression of α-SMA and promotes the transformation of fibroblasts to myofibroblasts; At the same time, the expression of Collagen-1 was enhanced, which suggested that the extracellular matrix was overconcentrated and eventually promoted the formation of pulmonary fibrosis. In vitro, we found that knockout and interference of MEN1 gene can significantly enhance radiation-induced fibrosis, and up-regulate the expression of downstream molecules Smad2 and Smad3 of TGF-ß signaling pathway, and down-regulate the expression of Smad7. Furthermore, it played an important role in regulating the process of radionuclide fibrosis. CONCLUSION: MEN1 plays a key role in the formation of pulmonary fibrosis by regulating the secretion of TGF-ß and the activation of TGF-ß/Smads signaling pathway.