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1.
Biotechnol Lett ; 43(10): 2045-2052, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34390483

RESUMO

OBJECTIVE: To investigate the protoplast preparation and transformation system of endophytic fungus Falciphora oryzae. RESULTS: F. oryzae strain obtained higher protoplast yield and effective transformation when treated with enzyme digestion solution containing 0.9 M KCl solution and 10 mg mL-1 glucanase at 30 °C with shaking at 80 rpm for 2-3 h. When the protoplasts were plated on a regenerations-agar medium containing 1 M sucrose, the re-growth rate of protoplasts was the highest. We successfully acquired green fluorescent protein-expressing transformants by transforming the pKD6-GFP vector into protoplasts. Further, the GFP expression in fungal hyphae possessed good stability and intensity during symbiosis in rice roots. CONCLUSIONS: This study provided a protoplast transformation system of F. oryzae, creating opportunities for future genetic research in other endophytic fungi.


Assuntos
Ascomicetos , Endófitos , Protoplastos/metabolismo , Transfecção/métodos , Ascomicetos/genética , Ascomicetos/metabolismo , Endófitos/genética , Endófitos/metabolismo , Proteínas Recombinantes de Fusão/genética , Simbiose/genética
2.
Int J Cancer ; 145(5): 1423-1431, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30664810

RESUMO

Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor-reactive T cells. The aim of this study was to determine the basic characteristics and clinical significance of the peripheral blood T-cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high-throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre- and post-treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.


Assuntos
Neoplasias Pulmonares/sangue , Receptores de Antígenos de Linfócitos T/sangue , Linfócitos T/imunologia , Estudos de Casos e Controles , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/sangue , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/patologia
3.
Biochem Biophys Res Commun ; 514(1): 308-315, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31036318

RESUMO

INTRODUCTION: Regulatory T cells (Tregs) are important in the tumor microenvironment. Many subpopulations of Tregs have participated in suppressing antitumor immunity. Recently, FOXA1+ Tregs were reported as a novel subset of Tregs that control autoimmune diseases. However, their clinical value in lung cancer is unknown. METHODS: We included 92 subjects in this study. Peripheral blood samples were collected from 15 lung cancer patients. Another 45 advanced stage lung cancer patients with malignant pleural effusion were enrolled for the analysis of FOXA1+ Tregs in pleural effusions. Lung cancer tissues were collected from 3 patients. In vitro experiments were conducted to ascertain the influence of FOXA1+ Tregs on T cells. Tumor-bearing mice model was utilized to explore the effects of Foxa1+ Treg on tumor growth and the prognoses. RESULTS: Our data demonstrated that FOXA1+ Tregs were increased in lung cancer. Moreover, patients with more FOXA1+ Tregs showed more liver metastases and poorer treatment responses. In vitro assays revealed that FOXA1+ Tregs inhibited the proliferation of T cells, the production of IFN-γ and IL-2 by T cells. FOXA1+ Tregs promoted tumor growth and indicated poor prognosis in the mice model of lung cancer. DISCUSSION: Collectively, our study is the first to investigate the suppressive function of FOXA1+ Tregs against T cells in lung cancer, and the results showed that FOXA1+ Tregs are markers of poor treatment responses in lung cancer patients. The inhibition of FOXA1+ Tregs represents a promising new strategy to enhance antitumor immunity.


Assuntos
Fator 3-alfa Nuclear de Hepatócito/metabolismo , Neoplasias Pulmonares/imunologia , Linfócitos T Reguladores/imunologia , Idoso , Animais , Antígeno B7-H1/metabolismo , Proliferação de Células , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Derrame Pleural Maligno/imunologia , Derrame Pleural Maligno/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/transplante , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Nat Prod ; 79(10): 2635-2643, 2016 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-27657857

RESUMO

To examine the effect of koumine, a Gelsemium alkaloid, on two experimental models of rheumatoid arthritis (RA), rats with adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) were administered koumine (0.6, 3, or 15 mg/kg/day) or vehicle through gastric gavage (i.g.). Clinical evaluation was performed via measurements of hind paw volume, arthritis index (AI) score, mechanical withdrawal threshold, organ weight, and by radiographic and histological examinations. Levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and antitype II collagen (CII) antibody were also examined. In rats with AIA, koumine reduced the AI score and mechanical allodynia of the injected hind paw in a dose-dependent manner and significantly inhibited increase in thymus and liver weights. In rats with CIA, koumine inhibited increase in hind paw volume, AI score, and mechanical allodynia in a dose-dependent manner and reduced joint space narrowing. Furthermore, koumine also attenuated the increase in the expression of IL-1ß and TNF-α, as well as the robust increase of serum anti-CII antibodies in response to immunization. These results suggested that koumine effectively attenuated arthritis progression in two rat models of RA and that this therapeutic effect may be associated with its immunoregulatory action.


Assuntos
Artrite Reumatoide/imunologia , Colágeno/farmacologia , Gelsemium/química , Alcaloides Indólicos/farmacologia , Animais , Artrite Experimental , Artrite Reumatoide/tratamento farmacológico , Citocinas/análise , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Feminino , Alcaloides Indólicos/química , Interleucina-1beta/análise , Masculino , Metotrexato/farmacologia , Estrutura Molecular , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Fator de Necrose Tumoral alfa/análise
5.
Sci Rep ; 14(1): 9276, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653742

RESUMO

Tumor-associated macrophages (TAMs) are a specific subset of macrophages that reside inside the tumor microenvironment. The dynamic interplay between TAMs and tumor cells plays a crucial role in the treatment response and prognosis of lung adenocarcinoma (LUAD). The study aimed to examine the association between TAMs and LUAD to advance the development of targeted strategies and immunotherapeutic approaches for treating this type of lung cancer. The study employed single-cell mRNA sequencing data to characterize the immune cell composition of LUAD and delineate distinct subpopulations of TAMs. The "BayesPrism" and "Seurat" R packages were employed to examine the association between these subgroups and immunotherapy and clinical features to identify novel immunotherapy biomarkers. Furthermore, a predictive signature was generated to forecast patient prognosis by examining the gene expression profile of immunotherapy-associated TAMs subsets and using 104 machine-learning techniques. A comprehensive investigation has shown the existence of a hitherto unidentified subgroup of TAMs known as RGS1 + TAMs, which has been found to have a strong correlation with the efficacy of immunotherapy and the occurrence of tumor metastasis in LUAD patients. CD83 was identified CD83 as a distinct biomarker for the expression of RGS1 + TAMs, showcasing its potential utility as an indicator for immunotherapeutic interventions. Furthermore, the prognostic capacity of the RTMscore signature, encompassing three specific mRNA (NR4A2, MMP14, and NPC2), demonstrated enhanced robustness when contrasted against the comprehensive collection of 104 features outlined in the published study. CD83 has potential as an immunotherapeutic biomarker. Meanwhile, The RTMscore signature established in the present study might be beneficial for survival prognostication.


Assuntos
Adenocarcinoma de Pulmão , Imunoterapia , Neoplasias Pulmonares , Macrófagos Associados a Tumor , Humanos , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/genética , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Imunoterapia/métodos , Prognóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Microambiente Tumoral/imunologia , Biomarcadores Tumorais , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Antígenos CD/metabolismo , Antígenos CD/genética
6.
Front Oncol ; 14: 1361879, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779090

RESUMO

As the second most common cancer in the world, the development of lung cancer is closely related to factors such as heredity, environmental exposure, and lung microenvironment, etc. Early screening and diagnosis of lung cancer can be helpful for the treatment of patients. Currently, CT screening and histopathologic biopsy are widely used in the clinical detection of lung cancer, but they have many disadvantages such as false positives and invasive operations. Microbes are another genome of the human body, which has recently been shown to be closely related to chronic inflammatory, metabolic processes in the host. At the same time, they are important players in cancer development, progression, treatment, and prognosis. The use of microbes for cancer therapy has been extensively studied, however, the diagnostic role of microbes is still unclear. This review aims to summarize recent research on using microbes for lung cancer detection and present the current shortcomings of microbes in collection and detection. Finally, it also looks ahead to the clinical benefits that may accrue to patients in the future about screening and early detection.

7.
Sci Rep ; 14(1): 11724, 2024 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778157

RESUMO

Accumulating evidence demonstrates that lncRNAs are involved in the regulation of the immune microenvironment and early tumor development. Immunogenic cell death occurs mainly through the release or increase of tumor-associated antigen and tumor-specific antigen, exposing "danger signals" to stimulate the body's immune response. Given the recent development of immunotherapy in lung adenocarcinoma, we explored the role of tumor immunogenic cell death-related lncRNAs in lung adenocarcinoma for prognosis and immunotherapy benefit, which has never been uncovered yet. Based on the lung adenocarcinoma cohorts from the TCGA database and GEO database, the study developed the immunogenic cell death index signature by several machine learning algorithms and then validated the signature for prognosis and immunotherapy benefit of lung adenocarcinoma patients, which had a more stable performance compared with published signatures in predicting the prognosis, and demonstrated predictive value for benefiting from immunotherapy in multiple cohorts of multiple cancers, and also guided the utilization of chemotherapy drugs.


Assuntos
Adenocarcinoma de Pulmão , Imunoterapia , Neoplasias Pulmonares , Aprendizado de Máquina , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/patologia , Imunoterapia/métodos , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Morte Celular Imunogênica , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética
8.
Front Pharmacol ; 15: 1173240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584599

RESUMO

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.

9.
Int J Radiat Oncol Biol Phys ; 119(4): 1222-1233, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266782

RESUMO

PURPOSE: Radioresistance of lung cancer poses a significant challenge when it comes to the treatment of advanced, recurrent, and metastatic cases. Ovarian tumor domain ubiquitin aldehyde binding 1 (OTUB1) is a key member of the deubiquitinase OTU superfamily. This protein is involved in various cellular functions, including cell proliferation, iron death, lipid metabolism, and cytokine secretion as well as immune response processes. However, its specific role and molecular mechanism in lung cancer radioresistance remain to be clarified. METHODS AND MATERIALS: The expression levels of OTUB1 in paired lung cancer tissues were determined by immunohistochemistry. In vitro and in vivo experiments were conducted to investigate the impact of OTUB1 on the growth and proliferation of lung cancer. Coimmunoprecipitation and Western blotting techniques were performed to examine the interaction between OTUB1 and CHK1. The DNA damage response was measured by comet tailing and immunofluorescence staining. KEGG pathways and Gene Ontology terms were analyzed based on RNA sequencing. RESULTS: Our findings reveal a high frequency of OTUB1 overexpression, which is associated with an unfavorable prognosis in patients with lung cancer. Through comprehensive investigations, we demonstrate that OTUB1 depletion impairs the process of DNA damage repair and overcomes radioresistance. In terms of the underlying mechanism, our study uncovers that OTUB1 deubiquitinates and stabilizes CHK1, which enhances CHK1 stability, thereby regulating DNA damage and repair. Additionally, we identify CHK1 as the primary downstream effector responsible for mediating the functional effects exerted by OTUB1 specifically in lung cancer. Importantly, OTUB1 has the potential to be a valuable marker for improving the efficacy of radiation therapy for lung adenocarcinoma. CONCLUSIONS: These findings unveil a novel role for OTUB1 in enhancing radioresistance by deubiquitination and stabilization of the expression of CHK1 in lung cancer and indicate that targeting OTUB1 holds great potential as an effective therapeutic approach for enhancing the efficacy of radiation therapy in lung cancer.


Assuntos
Quinase 1 do Ponto de Checagem , Progressão da Doença , Neoplasias Pulmonares , Tolerância a Radiação , Ubiquitinação , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Quinase 1 do Ponto de Checagem/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Camundongos , Proliferação de Células , Reparo do DNA , Cisteína Endopeptidases/metabolismo , Dano ao DNA , Proteases Específicas de Ubiquitina/metabolismo , Feminino , Camundongos Nus , Enzimas Desubiquitinantes/metabolismo , Estabilidade Proteica
10.
Front Pharmacol ; 14: 1205948, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37608885

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a long-lasting, continuously advancing, and irrevocable interstitial lung disorder with an obscure origin and inadequately comprehended pathological mechanisms. Despite the intricate and uncharted causes and pathways of IPF, the scholarly consensus upholds that the transformation of fibroblasts into myofibroblasts-instigated by injury to the alveolar epithelial cells-and the disproportionate accumulation of extracellular matrix (ECM) components, such as collagen, are integral to IPF's progression. The introduction of two novel anti-fibrotic medications, pirfenidone and nintedanib, have exhibited efficacy in decelerating the ongoing degradation of lung function, lessening hospitalization risk, and postponing exacerbations among IPF patients. Nonetheless, these pharmacological interventions do not present a definitive solution to IPF, positioning lung transplantation as the solitary potential curative measure in contemporary medical practice. A host of innovative therapeutic strategies are presently under rigorous scrutiny. This comprehensive review encapsulates the recent advancements in IPF research, spanning from diagnosis and etiology to pathological mechanisms, and introduces a discussion on nascent therapeutic methodologies currently in the pipeline.

11.
Mar Environ Res ; 183: 105841, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36512865

RESUMO

Prorocentrum donghaiense blooms occur annually in the East China Sea coastal waters, degrading ecosystem functions and impeding economic development. Dissolved organic nitrogen and phosphorus (DON and DOP) are the main components in the marine nutrient pools and are closely related to harmful algal blooms. From April to June 2019, a survey was conducted along the East China Sea coast (Sansha and Lianjiang counties) to investigate the relationship between dissolved organic nutrients and P. donghaiense bloom. Our findings showed that dinoflagellates dominated the phytoplankton community, and dissolved organic nutrients were the major factors influencing community structure during the P. donghaiense bloom. Redundancy analysis indicated that P. donghaiense abundance was primarily affected by DON in the Sansha area while it was primarily affected by DON and DOP in the Lianjiang area. Correlation analysis also confirmed a strong positive correlation between dissolved organic nutrients and P. donghaiense abundance both in the Sansha and Lianjiang coastal areas (p < 0.001). Furthermore, a culture experiment was carried out during the bloom to further investigate the effect of dissolved organic nutrients on the phytoplankton community structure. After 10 days of culture, dinoflagellates' relative abundance decreased from 97.1% to 28.2% in the inorganic treatment, whereas dinoflagellates continued to dominate the phytoplankton community in the organic treatment (76.9%). As a result, we propose that dissolved organic nutrients are responsible for the P. donghaiense bloom outbreak and promote the phytoplankton community shift from diatoms to dinoflagellates.


Assuntos
Dinoflagellida , Ecossistema , Proliferação Nociva de Algas , Fitoplâncton , China , Fósforo , Nutrientes , Nitrogênio
12.
Chem Commun (Camb) ; 59(84): 12621-12624, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37791621

RESUMO

Electrochemiluminescence nanoprobes with a core-shell-shell structure have been designed and applied for hyaluronidase detection. The nanoprobes can precipitate efficiently through target-regulation wettability for collection, and enrich near to the hydrophobic electrode surface through hydrophobic interaction to enhance the performance of the biosensor.


Assuntos
Técnicas Biossensoriais , Hialuronoglucosaminidase , Molhabilidade
13.
Int J Biol Sci ; 19(12): 3816-3829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564211

RESUMO

Cancer cells inevitably develop radioresistance during lung adenocarcinoma radiotherapy. However, the mechanisms are incompletely clarified. In this study, we show that FIBP protein expression in lung adenocarcinoma tissues is upregulated and associated with worse overall survival. Functionally, we find that depletion of FIBP inhibits lung adenocarcinoma progression and radioresistance in vitro and in vivo. Moreover, we uncover that FIBP interacts with STAT3 to enhance its transcriptional activity, thereby inducing the expression of the downstream target gene EME1. Importantly, we demonstrate that the biological effects of FIBP are partially dependent on EME1 in lung adenocarcinoma. Our work reveals that FIBP modulates the STAT3/EME1 axis to drive lung cancer progression and radioresistance, indicating that targeting FIBP may be a novel intervention strategy for lung adenocarcinoma radiotherapy.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/radioterapia , Adenocarcinoma/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteínas de Transporte/genética , Proteínas de Membrana/metabolismo
14.
Sci Rep ; 12(1): 13214, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918384

RESUMO

Most current research has focused on chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD) alone; however, it is important to understand the complex mechanism of COPD progression to LUAD. This study is the first to explore the unique and jointly molecular mechanisms in the pathogenesis of COPD and LUAD across several datasets based on a variety of analysis methods. We used weighted correlation network analysis to search hub genes in two datasets from public databases: GSE10072 and GSE76925. We explored the unique and jointly molecular mechanistic signatures of the two diseases in pathogenesis through enrichment analysis, immune infiltration analysis, and therapeutic targets analysis. Finally, the results were confirmed using real-time quantitative reverse transcription PCR. Fifteen hub genes were identified: GPI, EZH2, EFNA4, CFB, ENO1, SH3PXD2B, SELL, CORIN, MAD2L1, CENPF, TOP2A, ASPM, IGFBP2, CDKN2A, and ELF3. For the first time, SELL, CORIN, GPI, and EFNA4 were found to play a role in the etiology of COPD and LUAD. The LUAD genes identified were primarily involved in the cell cycle and DNA replication processes; COPD genes we found were related to ubiquitin-mediated proteolysis, ribosome, and T/B-cell receptor signaling pathways. The tumor microenvironment of LUAD pathogenesis was influenced by CD4 + T cells, type 1 regulatory T cells, and T helper 1 cells. T follicular helper cells, natural killer T cells, and B cells all impact the immunological inflammation in COPD. The results of drug targets analysis suggest that cisplatin and tretinoin, as well as bortezomib and metformin may be potential targeted therapy for patients with COPD combined LUAD. These signatures may be provided a new direction for developing early interventions and treatments to improve the prognosis of COPD and LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Consenso , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/genética , Transcriptoma , Microambiente Tumoral
15.
Front Cell Dev Biol ; 10: 769711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35211471

RESUMO

Lung adenocarcinoma (LUAD) is a frequently diagnosed cancer type, and many patients have already reached an advanced stage when diagnosed. Thus, it is crucial to develop a novel and efficient approach to diagnose and classify lung adenocarcinoma at an early stage. In our study, we combined in silico analysis and machine learning to develop a new five-gene-based diagnosis strategy, which was further verified in independent cohorts and in vitro experiments. Considering the heterogeneity in cancer, we used the MATH (mutant-allele tumor heterogeneity) algorithm to divide patients with early-stage LUAD into two groups (C1 and C2). Specifically, patients in C2 had lower intratumor heterogeneity and higher abundance of immune cells (including B cell, CD4 T cell, CD8 T cell, macrophage, dendritic cell, and neutrophil). In addition, patients in C2 had a higher likelihood of immunotherapy response and overall survival advantage than patients in C1. Combined drug sensitivity analysis (CTRP/PRISM/CMap/GDSC) revealed that BI-2536 might serve as a new therapeutic compound for patients in C1. In order to realize the application value of our study, we constructed the classifier (to classify early-stage LUAD patients into C1 or C2 groups) with multiple machine learning and bioinformatic analyses. The 21-gene-based classification model showed high accuracy and strong generalization ability, and it was verified in four independent validation cohorts. In summary, our research provided a new strategy for clinicians to make a quick preliminary assisting diagnosis of early-stage LUAD and make patient classification at the intratumor heterogeneity level. All data, codes, and study processes have been deposited to Github and are available online.

16.
BMC Med Genomics ; 15(1): 33, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193578

RESUMO

BACKGROUND: Precision medicine has increased the accuracy of cancer diagnosis and treatment, especially in the era of cancer immunotherapy. Despite recent advances in cancer immunotherapy, the overall survival rate of advanced NSCLC patients remains low. A better classification in advanced NSCLC is important for developing more effective treatments. METHOD: The calculation of abundances of tumor-infiltrating immune cells (TIICs) was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), xCell (xCELL), Tumor IMmune Estimation Resource (TIMER), Estimate the Proportion of Immune and Cancer cells (EPIC), and Microenvironment Cell Populations-counter (MCP-counter). K-means clustering was used to classify patients, and four machine learning methods (SVM, Randomforest, Adaboost, Xgboost) were used to build the classifiers. Multi-omics datasets (including transcriptomics, DNA methylation, copy number alterations, miRNA profile) and ICI immunotherapy treatment cohorts were obtained from various databases. The drug sensitivity data were derived from PRISM and CTRP databases. RESULTS: In this study, patients with stage 3-4 NSCLC were divided into three clusters according to the abundance of TIICs, and we established classifiers to distinguish these clusters based on different machine learning algorithms (including SVM, RF, Xgboost, and Adaboost). Patients in cluster-2 were found to have a survival advantage and might have a favorable response to immunotherapy. We then constructed an immune-related Poor Prognosis Signature which could successfully predict the advanced NSCLC patient survival, and through epigenetic analysis, we found 3 key molecules (HSPA8, CREB1, RAP1A) which might serve as potential therapeutic targets in cluster-1. In the end, after screening of drug sensitivity data derived from CTRP and PRISM databases, we identified several compounds which might serve as medication for different clusters. CONCLUSIONS: Our study has not only depicted the landscape of different clusters of stage 3-4 NSCLC but presented a treatment strategy for patients with advanced NSCLC.


Assuntos
Biologia Computacional , Neoplasias Pulmonares , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Aprendizado de Máquina , Prognóstico , Microambiente Tumoral/genética
17.
Front Microbiol ; 13: 845104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359723

RESUMO

Wild rice (Oryza granulata) is a natural resource pool containing abundant unknown endophytic fungi species. There are few reports on the endophytic fungi in wild rice. Here, one isolate recovered from wild rice roots was identified as a new species Pseudophialophora oryzae sp. nov based on the molecular phylogeny and morphological characteristics. Fluorescent protein-expressing P. oryzae was used to monitor the fungal colonization pattern. Hyphae invaded the epidermis to the inner cortex but not into the root stele. The inoculation of P. oryzae promoted the rice growth, with the growth parameters of chlorophyll content, shoot height, root length, fresh shoot weight, fresh root weight and dry weight increasing by 24.10, 35.32, 19.35, 90.00, 33.3, and 79.17%, respectively. P. oryzae induced up-regulation of nitrate transporter OsPTR9 and potassium transporter OsHAK16 by 7.28 ± 0.84 and 2.57 ± 0.80 folds, promoting nitrogen and potassium elements absorption. In addition, P. oryzae also conferred a systemic resistance against rice blast, showing a 72.65 and 75.63% control rate in sterile plates and potting conditions. This systemic resistance was mediated by the strongly up-regulated expression of resistance-related genes NAC, OsSAUR2, OsWRKY71, EL5, and PR1α. Since P. oryzae can promote rice growth, biomass and induce systemic disease resistance, it can be further developed as a new biogenic agent for agricultural production, providing a new approach for biocontrol of rice blast.

18.
Mar Pollut Bull ; 184: 114195, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208552

RESUMO

Horseshoe crabs (HSCs) are a group of ancient chelicerates with great ecological and biomedical importance. Food poisonings caused by the consumption of Asian HSCs have significant impacts on public health and safety. This study measured tetrodotoxin (TTX) concentrations in two HSC species across various life stages in May 2020 from the northern Beibu Gulf, their most important spawning and nursery habitats in China. The average TTX contents in both Carcinoscorpius rotundicauda and Tachypleus tridentatus ranged 6.2-8.0 µg/kg and 3.8-8.4 µg/kg, respectively. While sampling location, growth and molt stages have little influence on TTX distribution in both species, significantly higher levels of TTX were detected in hemolymph, but lower in pooled tissues of early-instar juvenile T. tridentatus. These results provide a regional view of TTX occurrence and distribution in HSCs during their spawning season, which are critical for future studies to enhance understanding of TTX dynamics and formation in HSCs.


Assuntos
Hemolinfa , Caranguejos Ferradura , Animais , Tetrodotoxina , China , Ecossistema
19.
Medicine (Baltimore) ; 100(10): e25010, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725881

RESUMO

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is still a constant threat to people's health. We aimed to identify the relationship between increased red cell distribution width (RDW) on admission and length of hospitalization in acute exacerbation of chronic obstructive pulmonary disease patients (AECOPD).Patients with AECOPD were recruited and divided into 3 groups based on RDW tertiles.Two hundred eighty six patients with AECOPD admitted to our department during January 1, 2017 and June 30, 2019 were enrolled in the study. According to the RDW tertiles (≤12.8%, 12.9% to 13.6%, >13.6%), the patients were divided into 3 groups. Length of stay was significantly related to RDW (P < .001) in AECOPD patients. Correlation analysis indicated that RDW was negatively associated with FEV1% predicted (r = -0.142, P = .016). However, RDW was positively associated with prolonged of stay (r = 0.298, P < .001) in AECOPD patients. Multivariate regression analysis discovered that RDW was independently associated with the length of hospitalization (P = .001). Receiver operating characteristic (ROC) curve showed that RDW was a good predictor of prolonged hospital stay in AECOPD patients, and the area under the curve (AUC) was 0.818 (95% CI: 0.769-0.868). The highest sensitivity to predict prolonged hospital stay was 83.8% and the specificity was 71.6% with the cut-off 13.35%.In conclusion, prolonged hospital stay in AECOPD patients was closely associated with increased RDW. Elevated RDW may be an independent predictor for prolonged hospitalization in AECOPD patients.


Assuntos
Índices de Eritrócitos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
Aging (Albany NY) ; 13(3): 3459-3482, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428606

RESUMO

Melanoma is a life-threatening form of skin cancer with an elevated risk of metastasis and high mortality rates. The prognosis and clinical outcomes of cancer immunotherapy in melanoma patients are influenced by immune cell infiltration in the tumor microenvironment (TME) and the expression of genetic factors. Despite reports suggesting that immune-classification may have a better prediction of prognosis compared to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM-classification, the definition of Immunoscore in melanoma is becoming a difficult challenge. In this study, we established and verified a 7-gene prognostic signature. Melanoma patients from the Cancer Genome Atlas (TCGA) were separated into a low-risk group and a high-risk group using the median risk score. Receiver operating characteristic (ROC) analysis for overall survival (OS) showed that the area under the curve (AUC) was 0.701 for 1 year, 0.726 for 3 years, and 0.745 for 5 years, respectively. Moreover, a nomogram was constructed as a practical prognostic tool, and the AUC was 0.829 for 3 years, and 0.803 for 5 years, respectively. Furthermore, we validated the above results in two datasets from the Gene Expression Omnibus (GEO) database and the relationship between 7-gene prognostic signature and immune infiltration estimated.


Assuntos
Linfócitos do Interstício Tumoral/metabolismo , Melanoma/genética , Neoplasias Cutâneas/genética , Bases de Dados Genéticas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Melanoma/mortalidade , Prognóstico , Intervalo Livre de Progressão , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
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