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Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.
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Adenocarcinoma de Pulmão , Ferroptose , Neoplasias Pulmonares , Humanos , Epigênese Genética , Ferroptose/genética , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genéticaRESUMO
Considerable evidence now indicates that cognitive impairment is primarily a vascular disorder. The depletion of smooth muscle 22 alpha (SM22α) contributes to vascular smooth muscle cells (VSMCs) switching from contractile to synthetic and proinflammatory phenotypes in the context of inflammation. However, the role of VSMCs in the pathogenesis of cognitive impairment remains undetermined. Herein, we showed a possible link between VSMC phenotypic switching and neurodegenerative diseases via the integration of multi-omics data. SM22α knockout (Sm22α-/-) mice exhibited obvious cognitive impairment and cerebral pathological changes, which were visibly ameliorated by the administration of AAV-SM22α. Finally, we confirmed that SM22α disruption promotes the expression of SRY-related HMG-box gene 10 (Sox10) in VSMCs, thereby aggravating the systemic vascular inflammatory response and ultimately leading to cognitive impairment in the brain. Therefore, this study supports the idea of VSMCs and SM22α as promising therapeutic targets in cognitive impairment to improve memory and cognitive decline.
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Proteínas dos Microfilamentos , Proteínas Musculares , Músculo Liso Vascular , Animais , Camundongos , Proliferação de Células , Células Cultivadas , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , FenótipoRESUMO
OBJECTIVE: To investigate the etiology and risk factors for unintentional injuries in children admitted to the pediatric intensive care unit (PICU), and to provide a basis for preventing these injuries and decreasing the mortality rate. METHODS: A retrospective analysis was performed on the clinical data of children with unintentional injuries admitted to the PICU from December 2012 to December 2017. RESULTS: A total of 102 children with unintentional injuries were admitted to the PICU, which accounted for 3.30% (102/3 087) of the overall PICU patients. The top three causes of unintentional injuries were food or drug poisoning, drowning, and foreign body ingestion and aspiration. The proportion of unintentional injuries in boys was significantly higher than in girls (P<0.05). The younger children had a significantly higher proportion of unintentional injuries (P<0.05). The cause of unintentional injuries was also related to age, and the common causes of unintentional injuries varied between different age groups. The proportion of unintentional injuries was not significantly different between children from urban and rural areas (P>0.05). The logistic regression analysis showed that the number of organs with dysfunction after unintentional injuries, especially respiratory, cardiac, neurological, renal and hematological involvement, was closely associated with the mortality rate of children with unintentional injuries (P<0.05); however, it is not an independent risk factor (P>0.05). CONCLUSIONS: Prevention is the key to decreasing the incidence of childhood unintentional injuries. Preventive measures should be taken based on patient's sex and age and the cause of unintentional injuries. The spread of first aid knowledge, improvement in emergency transportation, and more attention to organ protection may be useful for decreasing the mortality rate of children with unintentional injuries.
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Corpos Estranhos , Unidades de Terapia Intensiva Pediátrica , Ferimentos e Lesões , Criança , Feminino , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
The purpose of this study was to reveal the effect of inoculating autochthonous bacterial strains (Lactobacillus and Staphylococcus simulans) on the flavor profiles, microbial community, and metabolites, and to elucidate the potential mechanism of flavor formation in dry-cured duck. The results indicated that the inoculation of bacterial strains could improve the amount of lactic acid bacteria and Staphylococcus and reduce the counts of Enterobacteria. There was a significant difference in flavor profiles between samples inoculated with different strains. Hexanal-D, acetone, 3-methyl-1-butanol-D, thiophene, hexanal-M, propanal, pentanal, (Z)-2-penten-1-ol and ethanol-D were the potential biomarkers. A total of 70 differential metabolites were screened and identified. Amino acid metabolism and lipid metabolism were the key pathways for the production of flavor and metabolites in dry-cured duck. The results of this study will improve our understanding of the mechanism of flavor formation regarding the inoculation of autochthonous starter cultures.
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Aldeídos , Patos , Microbiologia de Alimentos , Animais , Fermentação , Bactérias/genética , Bactérias/metabolismo , MetabolomaRESUMO
A novel actinomycete, designated KLBMP 1284(T), was isolated from the surface-sterilized stems of a coastal halophyte Tamarix chinensis Lour. collected from the city of Nantong, Jiangsu Province, east China. The strain was found to have morphological and chemotaxonomic characteristics typical of members of the genus Streptomyces. Analysis of the 16S rRNA gene sequence of strain KLBMP 1284(T) revealed that the strain formed a distinct clade within the phylogenetic tree based on 16S rRNA gene sequences and the highest sequence similarity (99.43 %) was to Streptomyces sulphureus NRRL B-1627(T). 16S rRNA gene sequence similarity to other species of the genus Streptomyces was lower than 97 %. Based on DNA-DNA hybridization values and comparison of morphological and phenotypic data, KLBMP 1284(T) could be distinguished from the closest phylogenetically related species, Streptomyces sulphureus NRRL B-1627(T). Thus, based on these data, it is evident that strain KLBMP 1284(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces halophytocola sp. nov. is proposed. The type strain is KLBMP 1284(T) (= KCTC 19890(T) = NBRC 108770(T)).
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Filogenia , Plantas Tolerantes a Sal/microbiologia , Streptomyces/classificação , Tamaricaceae/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Endófitos/classificação , Endófitos/genética , Endófitos/isolamento & purificação , Ácidos Graxos/análise , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Caules de Planta/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Streptomyces/genética , Streptomyces/isolamento & purificaçãoRESUMO
A novel actinomycete, designated strain KLBMP 1262(T), was isolated from a coastal plant Dendranthema indicum (Linn.) Des Moul collected from the coastal region of Nantong, Jiangsu Province, in east China and was studied in detail for its taxonomic position. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain KLBMP 1262(T) is a member of the genus Amycolatopsis. The 16S rRNA gene sequence similarity indicated that strain KLBMP 1262(T) is most closely related to Amycolatopsis sulphurea DSM 46092(T) (97.96 %), Amycolatopsis ultiminotia RP-AC36(T) (97.50 %) and Amycolatopsis jejuensis N7-3(T) (97.44 %); similarity to other type strains of the genus Amycolatopsis was less than 97.0 %. The organism was determined to have chemical and morphological features consistent with its classification in the genus Amycolatopsis such as meso-diaminopimelic acid as the diagnostic diamino acid in the cell wall peptidoglycan and arabinose and galactose as the diagnostic sugars. The predominant menaquinone was determined to be MK-9 (H(4)). The polar lipids detected were phosphatidylmethylethanolamine, phosphatidylethanolamine, an unknown aminophospholipid, two unknown glycolipids and several unknown lipids. The major fatty acids were found to be C(16:0), iso-C(16:0) and iso-C(15:0). DNA-DNA relatedness data, together with phenotypic differences, clearly distinguished the isolate from its closest relatives. On the basis of these phenotypic and genotypic data, the isolate is considered to represent a novel species, for which the name A. jiangsuensis sp. nov. is proposed. The type strain is KLBMP 1262(T) (=KCTC 19885 (T) = NBRC 108679(T)).
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Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Chrysanthemum/microbiologia , Endófitos/classificação , Endófitos/isolamento & purificação , Técnicas de Tipagem Bacteriana , Carboidratos/análise , Parede Celular/química , China , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácido Diaminopimélico/análise , Ácidos Graxos/análise , Microscopia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análiseRESUMO
A halotolerant actinomycete strain, designated strain KLBMP 1305(T), was isolated from a salt marsh plant Dendranthema indicum (Linn.) Des Moul collected from the coastal region of Nantong, Jiangsu Province, in east China and was studied in detail for its taxonomic position. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain KLBMP 1305(T) is a member of the genus Saccharopolyspora. The 16S rRNA gene sequence similarity indicated that strain KLBMP 1305(T) was most closely related to 'Saccharopolyspora pathumthaniensis' S582(T) (99.31 %), 'Saccharopolyspora endophytica' YIM 61095(T) (99.17 %) and Saccharopolyspora tripterygii YIM 65359(T) (99.15 %); similarity to other type strains of the genus Saccharopolyspora was <97.2 %. The organism had chemical and morphological features consistent with its classification in the genus Saccharopolyspora such as meso-diaminopimelic acid as the diagnostic diamino acid in the cell wall peptidoglycan and arabinose and galactose as the diagnostic sugars. The predominant menaquinone was MK-9(H4). The polar lipids detected were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unknown glycolipid and an unknown lipid. The major fatty acids were iso-C16:0, iso-C15:0, anteiso-C15:0, anteiso-C17:0 and sum in feature 8 (18:1ω7c/18:1ω6c). The G+C content of the genomic DNA of the type strain was 68.7 mol%. DNA-DNA relatedness data, together with phenotypic differences, clearly distinguished the isolate from its closest relatives. On the basis of these phenotypic and genotypic data, the isolate represents a novel species, for which the name Saccharopolyspora dendranthemae sp. nov. is proposed. The type strain is KLBMP 1305(T) (=KCTC 19889(T) = NBRC 108675(T)).
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Chrysanthemum/microbiologia , Endófitos/isolamento & purificação , Endófitos/fisiologia , Saccharopolyspora/isolamento & purificação , Saccharopolyspora/fisiologia , Tolerância ao Sal , Áreas Alagadas , Técnicas de Tipagem Bacteriana , Composição de Bases , Sequência de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/metabolismo , Endófitos/classificação , Endófitos/genética , Metabolismo Energético , Ácidos Graxos , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Saccharopolyspora/classificação , Saccharopolyspora/genética , Análise de Sequência de DNA , Cloreto de Sódio , Vitamina K 2/análiseRESUMO
Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign lung tumor which generally presents as a solitary pulmonary nodule in middle-aged females. However, the PSP in some patients exhibits potentially malignant biological behavior, with recurrence and lymphatic or distant metastasis being observed. Case Description: We encountered a case of a 46-year-old female with an inordinately massive tumor 9.5 cm in diameter and a relatively high Ki-67 proliferation rate. Fine needle aspiration (FNA) played a significant but limited role in the preoperative diagnosis: the computed tomography (CT)-guided lung puncture biopsy was consistent with the typical pathology of PSP; however, endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) could not provide a definitive diagnosis. The patient ultimately underwent thoracoscopic resection and mediastinal lymph node dissection. Here, we provide a review of the literature on patients with PSP with malignant biological behavior to raise awareness of the malignant potential of PSP and describe our experience to inform future management. Conclusions: PSP lacks specificity in its clinical and radiological characteristics and has complex pathological manifestations. FNA is valuable in the diagnosis and differential diagnosis of PSP but involves the risk of misdiagnosis or missed diagnosis. Additionally, we believe that the accepted benign features of PSP need to be updated and that the potential malignant features of PSP should be carefully monitored. Surgical resection is curative but strict follow-up is crucial.
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Plants classified as Near Threatened (NT) are at high risk of becoming threatened because of anthropogenic interference and climate change. Especially in conservation efforts, such species have however long been overlooked. Here, we obtained 98,419 precise occurrence points for 2442 NT plants in China, and used species richness, species complementarity, and weighted endemism that consider all, endemic and narrow-ranged species in order to identify the diversity hotspots of NT plants. Then we evaluated the conservation effectiveness of current nature reserves for them. Our results indicate that the diversity hotspots of NT plants were mainly confined to southwestern and southern China, and only 35.87% of hotspots and 71.5% of species were protected by nature reserves. Numerous hotspots in southwestern China (e.g., Sichuan, Yunnan, Guangxi, and Hainan) were identified as conservation gaps. Given that NT plants include large proportions of endemic and narrow-ranged species, they represent an important value in conservation priority. So, more conservation efforts in the future should be tilted towards NT plants. Additionally, when comparing with the recently updated NT list, there are already 87 species raised to threatened categories, while 328 species were lowered to least concern, 56 species were now categorized as data deficient, and 119 species considered as uncertain due to changes of scientific names. It is essential to carry out a continuous assessment of species' threatened categories to realize targeting conservation.
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BACKGROUND: Regulator of G protein signaling 5 (RGS5), as a negative regulator of G protein-coupled receptor (GPCR) signaling, is highly expressed in arterial VSMCs and pericytes, which is involved in VSMC phenotypic heterogeneity and vascular remodeling in tumors. However, its role in normal and tumor vascular remodeling is controversial. METHODS: RGS5 knockout (Rgs5-KO) mice and RGS5 overexpression or knockdown in VSMCs in vivo by adeno-associated virus type 9 (AAV) carrying RGS5 cDNA or small hairpin RNA (shRNA) targeting RGS5 were used to determine the functional significance of RGS5 in vascular inflammation. RGS5 expression in the triple-negative (TNBCs) and non-triple-negative breast cancers (Non-TNBCs) was determined by immunofluorescent and immunohistochemical staining. The effect of breast cancer cell-conditioned media (BC-CM) on the pro-inflammatory phenotype of VSMCs was measured by phagocytic activity assays, adhesion assay and Western blot. RESULTS: We identified that knockout and VSMC-specific knockdown of RGS5 exacerbated accumulation and pyroptosis of pro-inflammatory VSMCs, resulting in vascular remodeling, which was negated by VSMC-specific RGS5 overexpression. In contrast, in the context of breast cancer tissues, the role of RGS5 was completely disrupted. RGS5 expression was increased in the triple-negative breast cancer (TNBC) tissues and in the tumor blood vessels, accompanied with an extensive vascular network. VSMCs treated with BC-CM displayed enhanced pro-inflammatory phenotype and higher adherent with macrophages. Furthermore, tumor-derived RGS5 could be transferred into VSMCs. CONCLUSIONS: These findings suggest that tumor microenvironment shifts the function of RGS5 from anti-inflammation to pro-inflammation and induces the pro-inflammatory phenotype of VSMCs that is favorable for tumor metastasis.
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Neoplasias , Proteínas RGS , Camundongos , Animais , Proteínas RGS/genética , Proteínas RGS/metabolismo , Remodelação Vascular/genética , Músculo Liso Vascular/metabolismo , Microambiente Tumoral , Camundongos Knockout , Homeostase , Inflamação , Proliferação de CélulasRESUMO
Vascular smooth muscle cells (VSMCs) can transdifferentiate into macrophage-like cells in the context of sustained inflammatory injury, which drives vascular hyperplasia and atherosclerotic complications. Using single-cell RNA sequencing, we identify that macrophage-like VSMCs are the key cell population in mouse neointimal hyperplasia. Sex-determining region Y (SRY)-related HMG-box gene 10 (Sox10) upregulation is associated with macrophage-like VSMC accumulation and pyroptosis in vitro and in the neointimal hyperplasia of mice. Tumor necrosis factor α (TNF-α)-induced Sox10 lactylation in a phosphorylation-dependent manner by PI3K/AKT signaling drives transcriptional programs of VSMC transdifferentiation, contributing to pyroptosis. The regulator of G protein signaling 5 (RGS5) interacts with AKT and blocks PI3K/AKT signaling and Sox10 phosphorylation at S24. Sox10 silencing mitigates vascular inflammation and forestalls neointimal hyperplasia in RGS5 knockout mice. Collectively, this study shows that Sox10 is a regulator of vascular inflammation and a potential control point in inflammation-related vascular disease.
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Músculo Liso Vascular , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Hiperplasia/patologia , Músculo Liso Vascular/metabolismo , Proliferação de Células/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piroptose , Fosfatidilinositol 3-Quinases/metabolismo , Transdiferenciação Celular , Neointima/metabolismo , Neointima/patologia , Camundongos Knockout , Inflamação/patologia , Miócitos de Músculo Liso/metabolismo , Células Cultivadas , Movimento Celular , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismoRESUMO
A novel isolate, designated strain KLBMP 1282(T) was isolated from the surface-sterilized leaves of a coastal halophyte Tamarix chinensis Lour., collected from Nantong, Jiangsu Province, east of China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that this strain belongs to the genus Pseudonocardia, being most closely related to Pseudonocardia kongjuensis LM 157(T) (98.33 %), Pseudonocardia autotrophica IMSNU 20050(T) (97.77 %), Pseudonocardia endophytica YIM 56035(T) (97.63 %), Pseudonocardia ammonioxydans H9 (T) (97.62 %) and Pseudonocardia compacta IMSNU 20111(T) (97.56 %); similarity to other type strains of the genus Pseudonocardia was <97.5 %. Chemotaxonomic data confirmed the affiliation of strain KLBMP 1282(T) to the genus Pseudonocardia. Strain KLBMP 1282(T) contained MK-8(H(4)) as the predominant ubiquinone and iso-C(16:0) as the major fatty acid. The polar lipids detected in strain KLBMP 1282(T) were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, one unknown phospholipid and four unknown glycolipids. The DNA G + C content of strain KLBMP 1282(T) was 73.1 mol %. The results of DNA-DNA hybridizations and the phylogenetic analysis, together with the phenotypic and biochemical tests, allowed the differentiation of strain KLBMP 1282(T) from strains of other recognized Pseudonocardia species. Therefore, strain KLBMP 1282(T) represents a novel species of the genus Pseudonocardia, for which the name Pseudonocardia nantongensis sp. nov. is proposed. The type strain is KLBMP 1282(T) (=KCTC 29053(T) = NBRC 108677(T)).
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Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Endófitos/classificação , Endófitos/isolamento & purificação , Tamaricaceae/microbiologia , Actinomycetales/genética , Actinomycetales/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Endófitos/genética , Endófitos/fisiologia , Ácidos Graxos/análise , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Filogenia , Folhas de Planta/microbiologia , RNA Ribossômico 16S/genética , Plantas Tolerantes a Sal/microbiologia , Análise de Sequência de DNA , Ubiquinona/análiseRESUMO
Impatiensyunlingensis S.X. Yu, Chang Y. Xia & J.H. Yu (Balsaminaceae), a species new to science discovered in Yunnan, China, is described and illustrated here, along with its phylogenetic position among other Impatiens species. Morphological, micro-morphological and molecular evidence is presented as an attestation of its novelty. Impatiensyunlingensis is similar to I.delavayi in having coarsely crenate leave margins, bracts in the upper part, ca. 4/5 length of the pedicels, saccate lower sepal with shallowly bifid spur, linear capsules, and elliptic-oblong, tuberculate seeds, but differs from I.delavayi with lateral sepals 4 (vs. 2), lateral united petal basal lobes subtriangular (vs. dolabriform), and seeds' surface equipped with tubercular ornamentation mostly covered with grain shaped appendages (vs. glabrous and without grain shaped appendages on the top).
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Background: Forkhead box P (FOXP) family was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. This study aimed to summarize the involvement of the FOXP family in non-small cell lung cancer (NSCLC). Methods: The UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), and Reverse transcription-quantitative polymerase chain reaction (RTâqPCR) were used to analyse the expression levels of the FOXP family in NSCLC. The prognostic impact was evaluated using Kaplan-Meier Plotter. MethSurv, UALCAN, and cBioPortal were applied to analyse the DNA methylation and mutation status of the FOXP family respectively. COEXPEDIA, STRING, and GeneMANIA were used to explore the interaction mechanism. Finally, TISIDB was used to investigate all of the immune-related characteristics regulated by the FOXP family. Results: The expression levels of FOXP1/3/4 were dysregulated in NSCLC tissues than that in normal tissues. Groups with low expression levels of FOXP1/4 and high expression levels of FOXP2/3 were associated with poor prognosis in NSCLC. The transcriptional levels of FOXP2/3/4 were correlated with DNA methylation in NSCLC. FOXP1/3/4 DNA methylation were correlated with prognosis. Pathway enrichment analysis indicated the FOXP family was mainly related to immune-related pathways. After DNA methylation, the correlations between FOXP family and immune factors were opposite to that before alteration in NSCLC. Conclusion: This study elucidated FOXP family could serve as vital diagnostic and prognostic biomarkers in NSCLC. Our study highlighted novel potential functions of FOXP family DNA methylation in regulation of immune-related signatures in NSCLC.
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Purpose: Chronic obstructive pulmonary disease (COPD) is a predominant cause of mortality worldwide. Autophagy, which depends on a lysosomal degradation pathway, plays an essential role in the occurrence of COPD. The aim of our study was to identify the potential function of autophagy and construct a BCL2-related competing endogenous RNA (ceRNA) network that induces autophagy in COPD. Methods: Blood sample data from GSE31568, GSE24709, and GSE61741 were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs in COPD and controls were identified via GEO2R. Transcription factors were obtained from FunRich. DIANA, miRDB, miRTarBase, and TargetScan were used to predict target genes of miRNAs. Autophagy genes were collected from the Human Autophagy Database (HADb). The GSE151052 dataset was used to identify autophagy-related differentially expressed genes in tissues. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted via Metascape and the STRING network. Spearman correlation analysis was used to analyze the relationship between autophagy-related differentially expressed genes and lung function. The BCL2-related ceRNA network was modeled by Cytoscape. Results: We obtained 41 differentially expressed miRNAs and 10 significantly different transcription factors. We identified 19 autophagy-related differentially expressed genes that were significantly different (P<0.05) in tissue samples. The most significant enrichment in Metascape was an autophagy item, which further confirmed autophagy participation in the occurrence of COPD. PPI network analysis found four genes (BCL2, BECN1, MAPK8, and ITPR1), among which BCL2 was correlated with both FEV1/FVC and FEV1 prediction. Finally, the BCL2-related ceRNA network was constructed to clarify the interaction of RNAs and occurrence of autophagy, including 18 miRNAs and 65 lncRNAs. Conclusion: We identified 19 autophagy-related differentially expressed genes that participated in COPD; among them, BCL2 was correlated with lung function, and a BCL2-related ceRNA network was constructed, which further revealed the potential mechanism of autophagy involvement in COPD.
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MicroRNAs , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Autofagia/genética , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genéticaRESUMO
Icariin and icaritin, the major active components of Epimedii Genus, are considered as promising drugs with anti-inflammatory, anti-aging and neuroprotective effects. Our previous studies have demonstrated that icariin and icaritin can protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity on dopaminergic neurons via insulin-like growth factor-1 receptor (IGF-1 receptor) signaling. In the present study, we aimed to evaluate the role of IGF-1 receptor signaling in mediating the anti-inflammatory effects of icariin and icaritin against lipopolysaccharide (LPS)-induced neuroinflammation as well as their biological regulation effects in midbrain primary astrocytes. Our results showed that both icariin and icaritin significantly inhibited LPS-induced mRNA expressions of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß). Pre-treatment with IGF-1 receptor antagonist JB-1 could significantly block the anti-inflammatory effects of icariin and icaritin on LPS-induced up-regulations of TNF-α, IL-1ß, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Under basal conditions of astrocytes, icariin and icaritin treatment alone increased the phosphorylation of ERK1/2 and AKT, which could be blocked by JB-1. Moreover, the mRNA expressions of glutamate transptor-1 (GLT-1) and glutamate-aspartate transporter (GLAST) could be up-regulated by icariin and icaritin in a time-dependent manner via IGF-1 receptor. Taken together, our results suggest for the first time that both icariin and icaritin exert regulatory effects in astrocytes under basal conditions and after an inflammatory challenge via IGF-1 receptor signaling pathway.
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Astrócitos/patologia , Flavonoides/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Receptor IGF Tipo 1/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , Humanos , Lipopolissacarídeos/imunologia , Mesencéfalo/citologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/patologia , Camundongos , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/patologia , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologiaRESUMO
Vascular smooth muscle cell (VSMC) senescence is a major driver of neointimal formation. We have demonstrated that circ-Sirt1 derived from the SIRT1 gene suppressed VSMC inflammation and neointimal formation. However, the effect of circ-Sirt1 inhibiting inflammation on VSMC senescence during neointimal hyperplasia remains to be elucidated. Here, we showed that circ-Sirt1 was highly expressed in young and healthy arteries, which was decreased in aged arteries and neointima of humans and mice. Overexpression of circ-Sirt1 delayed Ang II-induced VSMC senescence in vitro and ameliorated neointimal hyperplasia in vivo. Mechanically, circ-Sirt1 inhibited p53 activity at the levels of transcription and post-translation modulation. In detail, circ-Sirt1, on the one hand, interacted with and held p53 to block its nuclear translocation, and on the other hand, promoted SIRT1-mediated p53 deacetylation and inactivation. In conclusion, our data suggest that circ-Sirt1 is a novel p53 repressor in response senescence-inducing stimuli, and targeting circ-Sirt1 may be a promising approach to ameliorating aging-related vascular disease.
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With the formation of mesa-like cells at their surfaces, LiNbO3 thin films are useful for integrating high-density domain wall memory. However, the material is too hard and inert to etch the cells with inclined side edges that help to diminish polarization retention. Moreover, etching could damage the ferroelectricity of the film. To overcome these drawbacks in forming memory cells directly, we developed a technique to deposit two gapped electrodes in the film surface, without needing to etch the film. While applying an in-plane write voltage above a coercive voltage, the domain within the gap is reversibly switched along with the creation/erasure of conducting domain walls against the peripheral unswitched domain. This technique enables "on"/"off" current read of the written information. Unfortunately, the switched domain within the gap generally has poor retention and a weak wall current arises from the presence of a strong depolarization field. To overcome this problem, we fabricated a type of embedded electrode that diffuses thickness-wise into the LiNbO3 thin film to form a parallel-plate-like structure to screen the depolarization field. The switched domains now had good retention and carry large wall currents. Alternatively, without the embedded electrodes, the switched domains within the cells can be stabilized with increasing gap distance above a critical length of 320 nm. The two methods foreshadow the possibility in the future to fabricate damage-free LiNbO3 memory cells without etching.
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Background: Autophagy plays an important role in lung adenocarcinoma (LUAD). In this study, we aimed to explore the autophagy-related gene (ARG) expression pattern and to identify promising autophagy-related biomarkers to improve the prognosis of LUAD. Methods: The gene expression profiles and clinical information of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA), and validation cohort information was extracted from the Gene Expression Omnibus database. The Human Autophagy Database (HADb) was used to extract ARGs. Gene expression data were analyzed using the limma package and visualized using the ggplot2 package as well as the pheatmap package in R software. Functional enrichment analysis was also performed for the differentially expressed ARGs (DEARGs). Then, consensus clustering revealed autophagy-related tumor subtypes, and differentially expressed genes (DEGs) were screened according to the subtypes. Next, the univariate Cox and multivariate Cox regression analyses were used to identify independent prognostic ARGs. After overlapping DEGs and the independent prognostic ARGs, the predictive risk model was established and validated. Correlation analyses between ARGs and clinicopathological variables were also explored. Finally, the TIMER and TISIDB databases were used to further explore the correlation analysis between immune cell infiltration levels and the risk score as well as clinicopathological variables in the predictive risk model. Results: A total of 222 genes from the HADb were identified as ARGs, and 28 of the 222 genes were pooled as DEARGs. The most significant GO term was autophagy (p = 3.05E-07), and KEGG analysis results indicated that 28 DEARGs were significantly enriched in the ErbB signaling pathway (p < 0.001). Then, consensus clustering analysis divided the LUAD into two clusters, and a total of 168 DEGs were identified according to cluster subtypes. Then univariate and multivariate Cox regression analyses were used to identify 12 genes that could serve as independent prognostic indicators. After overlapping 168 DEGs and 12 genes, 10 genes (ATG4A, BAK1, CAPNS1, CCR2, CTSD, EIF2AK3, ITGB1, MBTPS2, SPHK1, ST13) were selected for the further exploration of the prognostic pattern. Survival analysis results indicated that this risk model identified the prognosis (p = 4.379E-10). Combined with the correlation analysis results between ARGs and clinicopathological variables, five ARGs were screened as prognostic genes. Among them, SPHK1 expression levels were positively correlated with CD4+ T cells and dendritic cell infiltration levels. Conclusions: In this study, we constructed a predictive risk model and identified a five autophagy subtype-related gene expression pattern to improve the prognosis of LUAD. Understanding the subtypes of LUAD is helpful to accurately characterize the LUAD and develop personalized treatment.
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Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson's disease. Ginsenoside Rg1, the most active ingredient of ginseng, has been reported to exert neuroprotective effects via estrogen and glucocorticoid receptors. The present study evaluated the involvement of the G protein-coupled estrogen receptor (GPER) in the anti-inflammatory effects of ginsenoside Rg1 against lipopolysaccharide (LPS)-induced microglia activation in the BV2 microglial cell line and ventral mesencephalic primary microglial culture. The pharmacological blockade and lentivirus-mediated small interfering RNA (siRNA) knockdown of GPER were used to study the underlying mechanism. Rg1 attenuated LPS-induced upregulation of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA and protein levels. The GPER antagonist G15 blocked the inhibitory effects of Rg1 and the GPER-specific agonist G1 on LPS-induced microglia activation. Rg1 mimicked the effects of G1 by inhibiting the LPS-induced activation of nuclear transcription factor-kappa B (NF-κB) and mitogen activated protein kinase signaling pathways, which was also blocked by G15. Moreover, lentivirus-mediated siRNA knockdown of GPER inhibited the anti-inflammatory effects of Rg1. Taken together, our results indicate that GPER is involved in the anti-inflammatory effects of Rg1 against LPS-induced microglia activation. These findings provide a new biological target of Rg1 for the treatment of neuroinflammatory disorders.