A bibliometric analysis of autophagy in lung diseases from 2012 to 2021.

Background: Autophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis. Methods: Publications were retrieved from the 2012-2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease. Results: A total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that "autophagy" and "apoptosis" were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases. Conclusion: The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19-related lung diseases.

A bibliometric analysis of NLRP3 inflammasome in acute lung injury/acute respiratory distress syndrome from 2010 to 2021.

Background: Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is essential in the pathogenesis of acute respiratory distress syndrome (ARDS), a fatal clinical syndrome that deteriorated from acute lung injury (ALI). This bibliometric study aims to offer a thorough insight into the scientific output about NLRP3 inflammasome in ALI/ARDS and explore the intellectual base, developing trajectory and emerging trends. Methods: We retrieved the literature from 2010 to 2021 from Science Citation Index Expanded (SCIE) database. Bibliometrix (3.1.4) R package and CiteSpace (5.8.R3) were used for further analysis and visualization. Results: A total of 508 English articles and reviews published from 2010 to 2021 were identified. The annual number of publications presented a rapidly developing trend especially in recent years. Among all the 42 countries, China was the most productive and most cited country, while the USA had the greatest impact. Peter A. Ward from the USA was the most productive corresponding author, and 4 of these top 10 corresponding authors were from China. The most cited reference was written by Ahmed (2017) of Zhejiang University in China. The Journal of Immunology had highest citation count and G-index. Furthermore, the major disciplines of research front have drifted from "Medicine, Medical, Clinical" to "Molecular, Biology, Immunology" over the past 12 years. In the co-occurring network, the terms "acute lung injury," "NLRP3 inflammasome," "interleukin-1ß," "NF-κB," and "NLRP3 activation" occurred most frequently, while in burst detection, "oxidative stress" had the highest burst strength. Co-citation network revealed that Cluster 2 "virus infection" was the most active area, including the most citation bursts. Cluster 0 "severe COVID-19" and Cluster 1 "dual inhibitor PTUPB" were emerging themes in recent years, and they involved the largest number of publications. Conclusions: This bibliometric analysis revealed a rapid growth trend of the relatively novel topic: NLRP3 inflammasome in ALI/ARDS. China was the largest contributor, while the USA offered the most landmark papers. The major disciplines of research front drifted from "Medicine, Medical, Clinical" to "Molecular, Biology, Immunology." In recent years, studies about the role of NLRP3 in COVID-19-associated ALI/ARDS and oxidative stress became hot spots.

The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases.

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle is disrupted. Itaconate is derived from cis-aconitate decarboxylation by cis-aconitate decarboxylase (ACOD1) in the mitochondrial matrix and is also known as immune-responsive gene 1 (IRG1). Studies have demonstrated that itaconate plays an important role in regulating signal transduction and posttranslational modification through its immunoregulatory activities. Itaconate is also an important bridge among metabolism, inflammation, oxidative stress, and the immune response. This review summarizes the structural characteristics and classical pathways of itaconate, its derivatives, and the compounds that release itaconate. Here, the mechanisms of itaconate action, including its transcriptional regulation of ATF3/IκBζ axis and type I IFN, its protein modification regulation of KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, and TFEB, and succinate dehydrogenase and glycolytic enzyme metabolic action, are presented. Moreover, the roles of itaconate in diseases related to inflammation and oxidative stress induced by autoimmune responses, viruses, sepsis and IRI are discussed in this review. We hope that the information provided in this review will help increase the understanding of cellular immune metabolism and improve the clinical treatment of diseases related to inflammation and oxidative stress.

Bibliometric analysis of global research trends on pyroptosis in lung disease.

Background: Pyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease. Methods: On February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results. Result: 1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: "NOD-like receptor3 (NLRP3) inflammasome", "inflammation", "oxidative stress", and "acute lung injury (ALI)". Conclusion: The research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.

Bibliometric analysis of global research trends on pyroptosis in lung disease

Background Pyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease. Methods On February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results. Result 1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: “NOD-like receptor3 (NLRP3) inflammasome”, “inflammation”, “oxidative stress”, and “acute lung injury (ALI)”. Conclusion The research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

Magnesium Hydride Ameliorates Endotoxin-Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell Apoptosis

Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1β, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1β pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1β pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.

Target-Based Virtual Screening and LC/MS-Guided Isolation Procedure for Identifying Phloroglucinol-Terpenoid Inhibitors of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 5 million deaths worldwide to date. Due to the limited therapeutic options so far available, target-based virtual screening with LC/MS support was applied to identify the novel and high-content compounds 1-4 with inhibitory effects on SARS-CoV-2 in Vero E6 cells from the plant Dryopteris wallichiana. These compounds were also evaluated against SARS-CoV-2 in Calu-3 cells and showed unambiguous inhibitory activity. The inhibition assay of targets showed that compounds 3 and 4 mainly inhibited SARS-CoV-2 3CLpro, with effective Kd values. Through docking and molecular dynamics modeling, the binding site is described, providing a comprehensive understanding of 3CLpro and interactions for 3, including hydrogen bonds, hydrophobic bonds, and the spatial occupation of the B ring. Compounds 3 and 4 represent new, potential lead compounds for the development of anti-SARS-CoV-2 drugs. This study has led to the development of a target-based virtual screening method for exploring the potency of natural products and for identifying natural bioactive compounds for possible COVID-19 treatment.

Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

Global Trends in Research of Macrophages Associated With Acute Lung Injury Over Past 10 Years: A Bibliometric Analysis.

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords "NLRP3" and "extracellular vesicles" appeared most frequently. Besides, researches on COVID-19-induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19-induced ALI and may be a target for the treatment of COVID-19.

Author Correction: Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

A Correction to this paper has been published: https://doi.org/10.1038/s41421-021-00267-0.

A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

[Moxibustion therapy in prevention and treatment of coronavirus disease 2019 (COVID-19): construction and application of non-contact diagnosis and treatment mode].

OBJECTIVE: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic. METHODS: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period (qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period (qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients. RESULTS: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68). CONCLUSION: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.

Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling

Background: Brain metastasis is a major cause of cancer death in patients with lung cancer. Sirtuin 1 and hsa-miR-217 have been identified to mediate the development of non-small cell lung cancer. Aims: To investigate the roles of hsa-miR-217, its target sirtuin 1, and the P53/KAI1 axis in the brain metastasis from non-small cell lung cancer. Study Design: Cell culture study. Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or sirtuin 1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to sirtuin 1was examined using a dual-luciferase reporter assay. Cell proliferation, migration, invasion, and related protein expression were detected to examine the effect of the miR-217/sirtuin 1 expression on metastasis. Results: PC-14/B cells expressed higher sirtuin 1 and lower P53 and KAI1 compared with BEAS-2B control cells (p<0.05). Sirtuin 1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (p=0.004), migration (p=0.001), and proliferation (p<0.05), whereas sirtuin 1 overexpression reversed all processes. sirtuin 1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase-9, and ß-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes. Conclusion: Hsa-miR-217 and its target sirtuin 1 acted as metastasis suppressor and promoter gene in non-small cell lung cancer, respectively. The hsa-miR-217/sirtuin 1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from non-small cell lung cancer. This axis might be a potential target for the treatment of brain metastasis of lung cancer.