Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
1.
RSC Adv ; 14(20): 13944-13945, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38686303

RESUMO

[This corrects the article DOI: 10.1039/D0RA05640E.].

2.
Opt Express ; 32(4): 6266-6276, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439334

RESUMO

Augmented reality (AR) display, as a next-generation innovative technology, is revolutionizing the ways of perceiving and communicating by overlaying virtual images onto real-world scenes. However, the current AR devices are often bulky and cumbersome, posing challenges for long-term wearability. Metasurfaces have flexible capabilities of manipulating light waves at subwavelength scales, making them as ideal candidates for replacing traditional optical elements in AR display devices. In this work, we propose and fabricate what we believe is a novel reflective polarization multiplexing gradient metasurface based on propagation phase principle to replace the optical combiner element in traditional AR display devices. Our designed metasurface exhibits different polarization modulations for reflected and transmitted light, enabling efficient deflection of reflected light while minimizing the impact on transmitted light. This work reveals the significant potential of metasurfaces in next-generation optical display systems and provides a reliable theoretical foundation for future integrated waveguide schemes, driving the development of next-generation optical display products towards lightweight and comfortable.

3.
Chem Biodivers ; : e202301923, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191840

RESUMO

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.

4.
Oxid Med Cell Longev ; 2023: 2561509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675243

RESUMO

Background: Atherosclerosis is considered the most common cause of morbidity and mortality worldwide. Athermanous plaque formation is pathognomonic of atherosclerosis. The main feature of atherosclerosis is the formation of plaque, which is inseparable from endothelial cells, vascular smooth muscle cells, and macrophages. MicroRNAs, a small highly conserved noncoding ribonucleic acid (RNA) molecule, have multiple biological functions, such as regulating gene transcription, silencing target gene expression, and affecting protein translation. MicroRNAs also have various pharmacological activities, such as regulating cell proliferation, apoptosis, and metabolic processes. It is noteworthy that many studies in recent years have also proved that microRNAs play a role in atherosclerosis. Methods: To summarize the functions of microRNAs in atherosclerosis, we reviewed all relevant articles published in the PubMed database before June 2022, with keywords "atherosclerosis," "microRNA," "endothelial cells," "vascular smooth muscle cells," "macrophages," and "cholesterol homeostasis," briefly summarized a series of research progress on the function of microRNAs in endothelial cells, vascular smooth muscle cells, and macrophages and atherosclerosis. Results and Conclusion. In general, the expression levels of some microRNAs changed significantly in different stages of atherosclerosis pathogenesis; therefore, MicroRNAs may become new diagnostic biomarkers for atherosclerosis. In addition, microRNAs are also involved in the regulation of core processes such as endothelial dysfunction, plaque formation and stabilization, and cholesterol metabolism, which also suggests the great potential of microRNAs as a therapeutic target.


Assuntos
Aterosclerose , MicroRNAs , Humanos , MicroRNAs/genética , Células Endoteliais , Aterosclerose/genética , Metabolismo dos Lipídeos , Colesterol
5.
J Pharm Biomed Anal ; 235: 115638, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37633162

RESUMO

Berberine, palmatine, physcion, rhein, calycosin-7-O-glucoside, and ferulic acid are six major active consituents that are present in Gushen Jiedu capsule (GSJD) extracts. The aim of this study was to determine the pharmacokinetics of the six active consituents in vivo by a rapid, sensitive, and precise UPLC-MS/MS method, which were compared between normal and diabetic nephropathy (DN) rats. Good separation of the target analytes and internal standards (ketoprofen and puerarin) was obtained on a Waters BEH C18 UPLC column with a mobile phase of 0.1 % formic acid acetonitrile-0.1 % formic acid water. All the calibration curves showed good linearity with a regression coefficient (r2) of ≥ 0.9908. The lower limits of quantification (LLOQ) for berberine, palmatine, physcion, rhein, calycosin-7-O-glucoside, and ferulic acid were 20, 2.5, 20, 20, 2.5, and 2.5 ng/mL, respectively. The relative standard deviations (RSDs) of intra-day and inter-day precision were all within 12.66 %, and the relative errors of intra-day and inter-day accuracy ranged from - 15.00 to 14.93 %. Good extraction recovery and matrix effects were obtained. The stability study confirmed the stability of the six analytes (RSD < 15 %). Finally, the data showed that the pharmacokinetic parameters (especially CLz/F, AUC and Tmax) of the six target analytes in DN rats were significantly different from those in normal rats. PK studies under pathological conditions could provide new thoughts to elucidate the underlying mechanism of GSJD and promote the clinical development of GSJD to treat DN.


Assuntos
Berberina , Diabetes Mellitus , Nefropatias Diabéticas , Animais , Ratos , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Nefropatias Diabéticas/tratamento farmacológico , Espectrometria de Massas em Tandem , Administração Oral , Glucosídeos
6.
J Heart Lung Transplant ; 42(11): 1578-1586, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37422146

RESUMO

BACKGROUND: The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. METHODS: Retrospective study of 401 consecutive patients undergoing PEA at our institution between August 2005 and March 2020 was performed. Primary outcome was the need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. RESULTS: Females (N = 203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p < 0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p < 0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final total pulmonary vascular resistance after PEA, 437 Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p < 0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p = 0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs 89.9% in males at 5 years, p < 0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p = 0.04). CONCLUSIONS: Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients are important. Further investigations into possible mechanisms to explain the differences are warranted.

7.
Microorganisms ; 11(5)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37317185

RESUMO

The Hexi Corridor is an arid region in northwestern China, where hypoliths are widely distributed, resulting from large amounts of translucent stone pavements. In this region, the water and heat distributions are uneven, with a descent gradient from east to west, which can affect the area's biological composition. The impact of environmental heterogeneity on the distribution of hypolithic microbial communities in this area is poorly understood, and this is an ideal location to investigate the factors that may influence the composition and structure of hypolithic microbial communities. An investigation of different sites with differences in precipitation between east and west revealed that the colonization rate decreased from 91.8% to 17.5% in the hypolithic community. Environmental heterogeneity influenced both the structure and function of the hypolithic community, especially total nitrogen (TN) and soil organic carbon (SOC). However, the effect on taxonomic composition was greater than that on ecological function. The dominant bacterial phyla in all sample sites were Cyanobacteria, Actinobacteria, Proteobacteria, and Deinococcus-Thermus, but the abundances varied significantly between the sampling sites. The eastern site had the highest relative abundance of Proteobacteria (18.43%) and Bacteroidetes (6.32%), while the western site had a higher relative abundance in the phyla Cyanobacteria (62%) and Firmicutes (1.45%); the middle site had a higher relative abundance of Chloroflexi (8.02%) and Gemmatimonadetes (1.87%). The dominant phylum in the fungal community is Ascomycota. Pearson correlation analysis showed that the soil's physicochemical properties were also associated with changes in community diversity at the sample sites. These results have important implications for better understanding the community assembly and ecological adaptations of hypolithic microorganisms.

8.
Artigo em Inglês | MEDLINE | ID: mdl-37329778

RESUMO

Triazoles are common agents for invasive fungal infections, while therapeutic drug monitoring is needed to improve antifungal efficacy and reduce toxicity. This study aimed to exploit a simple and reliable liquid chromatography-mass spectrometry method for high-throughput monitoring of antifungal triazoles in human plasma using UPLC-QDa. Triazoles in plasma were separated by chromatography on a Waters BEH C18 column and detected using positive ions electrospray ionization fitted with single ion recording. M+ for fluconazole (m/z 307.11) and voriconazole (m/z 350.12), M2+ for posaconazole (m/z 351.17), itraconazole (m/z 353.13) and ketoconazole (m/z 266.08, IS) were selected as representative ions in single ion recording mode. The standard curves in plasma showed acceptable linearities over 1.25-40 µg/mL for fluconazole, 0.47-15 µg/mL for posaconazole and 0.39-12.5 µg/mL for voriconazole and itraconazole. The selectivity, specificity, accuracy, precision, recovery, matrix effect, and stability met acceptable practice standards under Food and Drug Administration method validation guidelines. This method was successfully applied to the therapeutic monitoring of triazoles in patients with invasive fungal infections, thereby guiding clinical medication.


Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Humanos , Itraconazol , Voriconazol , Fluconazol , Espectrometria de Massas em Tandem/métodos , Triazóis , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes
9.
PLoS One ; 18(3): e0279050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36862630

RESUMO

OBJECTIVE: This systematic review aims to examine the influencing factors of undergraduates' depressive symptoms by summarizing the categories and intensity of the factors, to lay a foundation for subsequent research. METHODS: Two authors independently searched in Medline (Ovid), Embase (Ovid), Scopu, PsycINFO, PsycARTICLES, the Chinese Scientific Journal Database (VIP Database), China National Knowledge database (CNKI), and the WanFang database for cohort studies related to the influencing factors affecting depressive symptoms among undergraduates published prior to September 12, 2022. Adjusted Newcastle-Ottawa scale (NOS) was used to assess the risk of bias. Meta-analyses of regression coefficient estimates were performed to calculate pooled estimates with R 4.0.3 software. RESULTS: A total of 73 cohort studies were included, involving 46362 participants from 11 countries. Factors affecting depressive symptoms were classified into relational, psychological, predictors of response to trauma, occupational, sociodemographic and lifestyle factors. In Meta-analysis, 4 of 7 influencing factors were revealed to be statistically significant: negative coping (B = 0.98, 95%CI: 0.22-1.74), rumination (B = 0.06, 95%CI: 0.01-0.11), stress (OR = 0.22, 95%CI: 0.16-0.28) and childhood abuse (B = 0.42, 95%CI:0.13-0.71). No significant association was found in positive coping, gender and ethnicity. LIMITATIONS: The current studies have the problems of inconsistent use of scales and large heterogeneity of research design, making it difficult to summarize, which is expected to be further improved in future research. CONCLUSION: This review evidences the importance of several influencing factors of depressive symptoms among undergraduates. We advocate for more high-quality studies with more coherent and appropriate study designs and outcome measurement approaches in this field. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration CRD42021267841.


Assuntos
Adaptação Psicológica , Depressão , Estudantes , Humanos , China , Bases de Dados Factuais , Depressão/epidemiologia , Estudantes/psicologia
10.
Front Endocrinol (Lausanne) ; 13: 1074638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568094

RESUMO

Gases such as hydrogen sulfide, nitric oxide and sulfur dioxide have important regulatory effects on the endocrine and physiological processes of the body and are collectively referred to as "gas signaling molecules". These gas signaling molecules are also closely related to Alzheimer's disease, the inflammatory response and depression. In this paper, we introduce the production and metabolic pathways of NO, H2S and SO2 in living organisms and review the regulatory functions of gas signaling molecules in the endocrine system and their mechanisms in relation to their clinical applications. This work will provide a basis for finding targets for intervention and establishing novel prevention and treatment strategies for related diseases.


Assuntos
Sulfeto de Hidrogênio , Transdução de Sinais , Humanos , Transdução de Sinais/fisiologia , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Dióxido de Enxofre
11.
Front Psychol ; 13: 929359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967692

RESUMO

The productivity gains generated by innovation are the root cause of long-term economic growth. In this paper, two empirical hypotheses are proposed to clarify our view: the trade turnover of technology market and intellectual property protection are important factors to stimulate innovation; The main channel of communication is through the increase of research staff and R&D funds. The empirical research result show that: (1) The greater the technology trade volume, the greater the incentive to regional innovation activities, the greater the number of regional patents; (2) About the intellectual property protection, The higher the protection intensity is, the greater the incentive is to regional innovation activities and the greater the number of regional patents. Different from relevant researches, this paper discusses the decisive role of market activity and legal environment on regional innovation behavior from the perspective of technology trade and patent protection, and emphasizes the theoretical significance of market and legal system from a more general perspective.

12.
Cancer Gene Ther ; 29(12): 1951-1960, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35902729

RESUMO

Monocytes/macrophages, a plastic and heterogeneous cell population of the tumor microenvironment (TME), can constitute a major component of most solid tumors. Under the pressure of rapid proliferation of the tumor, monocytes/macrophages can be educated and foster immune tolerance via metabolic reprogramming. Our studies have shown that the activation of FABP5, a lipid-binding protein, decreases the rate of ß-oxidation causing the accumulation of lipid droplets in monocytes. We found that hepatocellular carcinoma cells (HCC) increased IL-10 secretion by monocytes, which depended on the expression of FABP5 and suppressing of the PPARα pathway. Moreover, the elevated level of IL-10 promotes PD-L1 expression on Treg cells via the JNK-STAT3 pathway activation. We also observed that elevation of FABP5 in monocytes was negatively related to HCC patients' overall survival time. Thus, FABP5 promotes monocyte/macrophage lipid accumulation, fosters immune tolerance formation, and might represent itself as a therapeutic target in both tumor-associated monocytes (TAMs) and cancer cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Monócitos/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Interleucina-10/metabolismo , Interleucina-10/uso terapêutico , Privilégio Imunológico , Neoplasias Hepáticas/metabolismo , Linfócitos T Reguladores/metabolismo , Macrófagos , Microambiente Tumoral , Lipídeos/uso terapêutico , Linhagem Celular Tumoral , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/uso terapêutico
13.
Artigo em Inglês | MEDLINE | ID: mdl-35412454

RESUMO

A bacterial strain, designated S9-5T, was isolated from moraine samples collected from the north slope of Mount Everest at an altitude of 5 500 m above sea level. A polyphasic study confirmed the affiliation of the strain with the genus Sphingomonas. Strain S9-5T was an aerobic, Gram-stain-negative, non-spore-forming, non-motile and rod-shaped bacterium that could grow at 10-40 °C, pH 5-8 and with 0-9 % (w/v) NaCl. Q-10 was its predominant respiratory menaquinone. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminophospholipid and eight unidentified lipids comprised the polar lipids of strain S9-5T. Its major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C16 : 0. The G+C content was 65.75mol%. Phylogenetic analysis based on 16S rRNA sequences showed that strain S9-5T was phylogenetically closely related to Sphingomonas panaciterrae DCY91T (98.17 %), Sphingomonas olei K-1-16T (98.11 %) and Sphingomonas mucosissima DSM 17494T (97.39 %). The average nucleotide identity values among strain S9-5T and Sphingomonas panaciterrae DCY91T, Sphingomonas olei K-1-16T and Sphingomonas mucosissima DSM 17494T were 78.82, 78.87 and 78.29 %, respectively. Based on the morphological, physiological and chemotaxonomic data, strain S9-5T (=JCM 34750T=GDMCC 1.2714T) should represent a novel species of the genus Sphingomonas, for which we propose the name Sphingomonas radiodurans sp. nov.


Assuntos
Sphingomonas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo
14.
Front Oncol ; 12: 795159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242705

RESUMO

Due to the emergence of traditional drug resistance in tumor treatment, the anti-cancer therapies are facing multiple challenges. Immunotherapy, as a new and universal treatment, has been gradually concerned. The macrophages, as an important part of the immune system, play an important role in it. Many studies have shown that immune state is essential in cancer progression and prognosis, rebuilding the architecture and functional orientation of the tumor region. Most tumors are complex ecosystems that change temporally and spatially under the pressure of proliferation, apoptosis, and extension of every cell in the microenvironment. Here, we review how macrophages states can be dynamically altered in different metabolic states and we also focus on the formation of immune exhaustion. Finally, we look forward to the explorations of clinical treatment for immune metabolism process.

15.
Int J Cancer ; 150(9): 1525-1536, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985768

RESUMO

The acquisition of ectopic type I fibroblast growth factor receptor (FGFR1) is a common feature of prostate cancer (PCa), the most frequently diagnostic cancer in men. However, how ectopic FGFR1 contributes to PCa progression is not well understood. In our study we showed that ablation of FGFR1 in DU145 human PCa cells changed the cell metabolite profile. Among the changes, the choline metabolism profile was the most significantly altered by FGFR1 ablation. Detailed characterization revealed that ablation of FGFR1 altered expression of multiple choline metabolism enzymes. Among the changes of FGFR1-regulated choline metabolic enzymes, downregulation of choline kinase α (CHKA) is the most prominent changes, which phosphorylates free choline to phosphocholine. Ablation of FGFR1 blunted the activity of choline to promote cell proliferation and survival. Furthermore, depletion of CHKA compromised FGF signaling activity in DU145 cells. We also first time demonstrated that FGFR1 formed complex with CHKA, suggesting that FGFR1 regulated CHKA at the posttranslational level. Together with the previous report that ectopic FGFR1 contributes to PCa progression and metastasis, our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by dysregulating choline metabolism, and that the crosstalk between FGFR1-choline metabolism can be a potential target for managing PCa progression.


Assuntos
Colina , Neoplasias da Próstata , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Linhagem Celular Tumoral , Proliferação de Células , Colina/metabolismo , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais
16.
Chem Biol Drug Des ; 99(1): 83-91, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34288496

RESUMO

Lung cancer is the leading cause of cancer death. Pyronaridine, a synthetic drug of artemisinin, has been used in China for over 30 years for the treatment of malaria, but its effect on non-small cell lung cancer (NSCLC) cells is rarely reported. In this study, we determined the efficacy of pyronaridine in four different NSCLC cell lines and explored its mechanism in H1975. The data showed that pyronaridine could upregulate the expression of TNF-related apoptosis-inducing ligand (TRAIL)-mediated death receptor 5 to promote cellular apoptosis. Meanwhile, the JNK (c-Jun N-terminal kinase) level was detected to be significantly increased after treating with pyronaridine. We used JNK inhibitor and found that it could partially inhibit cell apoptosis. The results showed that epidermal growth factor receptor (EGFR), PI3K, and AKT were downregulated after the treatment of pyronaridine. In summary, pyronaridine can selectively kill NSCLC by regulating TRAIL-mediated apoptosis and downregulating the protein level of EGFR. It is a promising anticancer drug for NSCLC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Naftiridinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Naftiridinas/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Semin Thorac Cardiovasc Surg ; 34(1): 315-323, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33984481

RESUMO

Pulmonary endarterectomy (PEA) is the main treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Postoperative unfractionated heparin dosing can be monitored by activated partial thromboplastin time (APTT) or by anti-factor Xa activity (anti-Xa). In pseudo heparin resistance, APTT response to heparin is blunted due to elevated Factor VIII (FVIII) which can underestimate anticoagulation. We examined possible pseudo heparin resistance after PEA and assessed the impact of FVIII. APTT response to heparin before and after operation was determined in 13 PEA patients anticoagulated with unfractionated heparin. APTT and anti-Xa concordance was analyzed from paired postoperative samples, and antithrombin, fibrinogen and FVIII levels were measured. Single-cell RNA sequencing was used to characterize FVIII gene expression in PEA specimens of 5 patients. APTT response to heparin was blunted after PEA. APTT and anti-Xa were discordant in 36% of postoperative samples and most common discordant patterns were subtherapeutic APTT with therapeutic (16%) or supratherapeutic (11%) anti-Xa. Overall, APTT underestimated anticoagulation relative to anti-Xa in one-third of the samples. FVIII levels were elevated before surgery, increased substantially 1 and 3 days (median 4.32 IU/mL) after PEA, and were higher in discordant than concordant samples. Single-cell RNA sequencing showed FVIII gene expression in PEA specimen endothelial cells. Pseudo heparin resistance is common after PEA likely due to highly elevated postoperative FVIII levels indicating that anti-Xa reflects postoperative heparinization better than APTT in these patients. FVIII production by the pulmonary artery endothelium may participate in local prothrombotic processes important for CTEPH pathogenesis.


Assuntos
Hemostáticos , Trombose , Anticoagulantes/uso terapêutico , Endarterectomia/efeitos adversos , Células Endoteliais/metabolismo , Fator VIII/metabolismo , Inibidores do Fator Xa/uso terapêutico , Heparina , Humanos , Trombose/etiologia , Trombose/cirurgia , Resultado do Tratamento
18.
J Clin Med ; 10(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34768716

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. METHODS: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. RESULTS: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4+ T cells and CD8+IFNγ+ T cells were significantly increased. TCGA data showed that IRF3 expression was an unfavorable prognostic factor in MESO patients. IRF3 expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. CONCLUSION: IRF3 could play a critical role in the tumor immune microenvironment of MESO.

19.
Commun Biol ; 4(1): 914, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312483

RESUMO

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.


Assuntos
Antineoplásicos/farmacologia , Radioisótopos de Césio/farmacologia , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteína Relacionada a TNFR Induzida por Glucocorticoide/genética , Mesotelioma Maligno/genética , Fatores de Necrose Tumoral/genética , Animais , Linhagem Celular Tumoral , Feminino , Proteína Relacionada a TNFR Induzida por Glucocorticoide/metabolismo , Humanos , Mesotelioma Maligno/terapia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fatores de Necrose Tumoral/metabolismo
20.
Sci Transl Med ; 13(589)2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853932

RESUMO

Malignant pleural mesothelioma (MPM) is an intractable disease with an extremely poor prognosis. Our clinical protocol for MPM of subablative radiotherapy (RT) followed by radical surgery achieved better survival compared to other multimodal treatments, but local relapse and metastasis remain a problem. This subablative RT elicits an antitumoral immune response that is limited by the immunosuppressive microenvironment generated by regulatory T (Treg) cells. The antitumor effect of immunotherapy to simultaneously modulate the immune activation and the immune suppression after subablative RT has not been investigated in MPM. Herein, we demonstrated a rationale to combine interleukin-15 (IL-15) superagonist (IL-15SA) and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonist (DTA-1) with subablative RT in mesothelioma. IL-15SA boosted the systemic expansion of specific antitumoral memory CD8+ T cells that were induced by RT in mice. Their effect, however, was limited by the up-regulation and activation of Treg cells in the radiated tumor microenvironment. Hence, selective depletion of intratumoral Treg cells through DTA-1 enhanced the benefit of subablative RT in combination with IL-15SA. The addition of surgical resection of the radiated tumor in combination with IL-15SA and DTA-1 maximized the benefit of RT and was accompanied by a reproducible abscopal response in a concomitant tumor model. These data support the development of clinical trials in MPM to test such treatment options for patients with locally advanced or metastatic tumors.


Assuntos
Mesotelioma , Neoplasias Pleurais , Animais , Linfócitos T CD8-Positivos , Humanos , Imunidade , Mesotelioma/terapia , Camundongos , Recidiva Local de Neoplasia , Neoplasias Pleurais/terapia , Linfócitos T Reguladores , Microambiente Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...