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1.
Cancer Lett ; 591: 216902, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641310

RESUMO

Platelets have received growing attention for their roles in hematogenous tumor metastasis. However, the tumor-platelet interaction in osteosarcoma (OS) remains poorly understood. Here, using platelet-specific focal adhesion kinase (FAK)-deficient mice, we uncover a FAK-dependent F3/TGF-ß positive feedback loop in OS. Disruption of the feedback loop by inhibition of F3, TGF-ß, or FAK significantly suppresses OS progression. We demonstrate that OS F3 initiated the feedback loop by increasing platelet TGF-ß secretion, and platelet-derived TGF-ß promoted OS F3 expression in turn and modulated OS EMT process. Immunofluorescence results indicate platelet infiltration in OS niche and we verified it was mediated by platelet FAK. In addition, platelet FAK was proved to mediate platelet adhesion to OS cells, which was vital for the initiation of F3/TGF-ß feedback loop. Collectively, these findings provide a rationale for novel therapeutic strategies targeting tumor-platelet interplay in metastatic OS.


Assuntos
Plaquetas , Neoplasias Ósseas , Transição Epitelial-Mesenquimal , Osteossarcoma , Fator de Crescimento Transformador beta , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/genética , Animais , Plaquetas/metabolismo , Plaquetas/patologia , Fator de Crescimento Transformador beta/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/genética , Humanos , Linhagem Celular Tumoral , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Retroalimentação Fisiológica , Camundongos , Camundongos Knockout , Progressão da Doença , Transdução de Sinais , Adesividade Plaquetária
2.
Front Oncol ; 14: 1359807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500663

RESUMO

The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R "Bibliometrix" package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis.

3.
Adv Sci (Weinh) ; : e2310167, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502871

RESUMO

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

4.
Front Immunol ; 14: 1257254, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720221

RESUMO

Chordoma is a rare malignant bone tumor with limited therapeutic options, which is resistant to conventional chemotherapy and radiotherapy, and targeted therapy is also shown with little efficacy. The long-standing delay in researching its mechanisms of occurrence and development has resulted in the dilemma of no effective treatment targets and no available drugs in clinical practice. In recent years, the role of the tumor immune microenvironment in driving tumor growth has become a hot and challenging topic in the field of cancer research. Immunotherapy has shown promising results in the treatment of various tumors. However, the study of the immune microenvironment of chordoma is still in its infancy. In this review, we aim to present a comprehensive reveal of previous exploration on the chordoma immune microenvironment and propose promising immunotherapy strategies for chordoma based on these characteristics.


Assuntos
Cordoma , Humanos , Cordoma/terapia , Imunoterapia , Microambiente Tumoral
5.
Front Oncol ; 13: 1192472, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404767

RESUMO

Purpose: Anlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS. Materials and Methods: In this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC. Results: We found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis. Conclusion: Tocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS.

6.
Sci Rep ; 13(1): 9746, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328516

RESUMO

Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Feminino , Hibridização in Situ Fluorescente/métodos , Amplificação de Genes , Inteligência Artificial , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Biomarcadores Tumorais/genética
8.
Sci Rep ; 13(1): 8187, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210457

RESUMO

Morphological parameters of knee joint are related to race and nationality. At present, knee prosthesis come from white male population. Due to the mismatch between the prosthesis and other ethnic groups, the prosthesis life span is reduced, revision surgery and the patients' economic burden are increased. There is no data of the Mongolian ethnic group. In order to treat patients more accurately, we measured the Mongolian data of the femoral condyle. A total of 122 knee joints were scanned in 61 volunteers (21 males and 40 females) with an average age of 23.259 ± 1.395 years. The Mimics software was used to reconstruct the 3D image and measure the data of each line. The data were analyzed by statistical methods such as t test, and P < 0.05 was taken as the significant. 122 normal femoral condyle data were obtained. The mean transverse diameter of femoral condyle is 76.472 ± 5.952 mm, medial condyle is 29.259 ± 11.461 mm, and the sagittal diameter of the medial condyle was 56.758 ± 4.163 mm. The transverse diameter of the lateral femoral condyle is 29.388 ± 3.157 mm, the sagittal diameter of the lateral condyle is 58.937 ± 3.527 mm and the femoral plane rate is 1.264 ± 0.072. (1) There was no statistical significance in the left and right knee joint data (P > 0.05). (2) The different genders data of femoral condyle were statistically significant (P < 0.05). (3) Compared with other nationalities and races, the data of femoral condyle are different. (4) There are differences between femoral surface ratio and mainstream prosthesis data.


Assuntos
Artroplastia do Joelho , Relevância Clínica , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Articulação do Joelho/cirurgia , Fêmur/cirurgia , Artroplastia do Joelho/métodos , Epífises/cirurgia
9.
J Immunother Cancer ; 11(4)2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37185233

RESUMO

BACKGROUND: Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets. METHODS: Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC). RESULTS: The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo. CONCLUSIONS: Our study implicates that the CCL5-CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5-CCR5 axis is a potential therapeutic target in chordoma.


Assuntos
Cordoma , Macrófagos Associados a Tumor , Humanos , Animais , Camundongos , Macrófagos Associados a Tumor/metabolismo , Cordoma/tratamento farmacológico , Cordoma/metabolismo , Macrófagos , Maraviroc/metabolismo , Modelos Animais de Doenças , Microambiente Tumoral , Quimiocina CCL5/metabolismo
10.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674804

RESUMO

The nuclear receptors-liver X receptors (LXR α and ß) are potential therapeutic targets in cardiovascular and neurodegenerative diseases because of their key role in the regulation of lipid homeostasis and inflammatory processes. Specific oxy(phyto)sterols differentially modulate the transcriptional activity of LXRs providing opportunities to develop compounds with improved therapeutic characteristics. We isolated oxyphytosterols from Sargassum fusiforme and synthesized sidechain oxidized sterol derivatives. Five 24-oxidized sterols demonstrated a high potency for LXRα/ß activation in luciferase reporter assays and induction of LXR-target genes APOE, ABCA1 and ABCG1 involved in cellular cholesterol turnover in cultured cells: methyl 3ß-hydroxychol-5-en-24-oate (S1), methyl (3ß)-3-aldehydeoxychol-5-en-24-oate (S2), 24-ketocholesterol (S6), (3ß,22E)-3-hydroxycholesta-5,22-dien-24-one (N10) and fucosterol-24,28 epoxide (N12). These compounds induced SREBF1 but not SREBP1c-mediated lipogenic genes such as SCD1, ACACA and FASN in HepG2 cells or astrocytoma cells. Moreover, S2 and S6 enhanced cholesterol efflux from HepG2 cells. All five oxysterols induced production of the endogenous LXR agonists 24(S)-hydroxycholesterol by upregulating the CYP46A1, encoding the enzyme converting cholesterol into 24(S)-hydroxycholesterol; S1 and S6 may also act via the upregulation of desmosterol production. Thus, we identified five novel LXR-activating 24-oxidized sterols with a potential for therapeutic applications in neurodegenerative and cardiovascular diseases.


Assuntos
Doenças Neurodegenerativas , Fitosteróis , Humanos , Receptores X do Fígado , Esteróis/farmacologia , Receptores Nucleares Órfãos/genética , Hidroxicolesteróis , Doenças Neurodegenerativas/tratamento farmacológico , Colesterol
11.
J Ethnopharmacol ; 303: 115930, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36403744

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Weifuchun capsule (WFC) is a traditional Chinese patent medicine for chronic atrophic gastritis (CAG) in clinic. However, the mechanism of action of WFC for CAG still remains unclear due to its complex composition. AIM OF THE STUDY: The study was projected to uncover the mechanism of action of WFC and the corresponding pharmacodynamic substance of WFC against CAG as well as providing a standard example for the research of traditional Chinese medicine (TCM) from the perspective of the network and the system. MATERIALS AND METHODS: We identified the compounds of WFC through LC-MS/MS analysis and performed a systematic network targets analysis for WFC in the treatment of CAG which thoroughly described the mechanism of action of WFC for CAG. Based on analysis integrating omics data and algorithms, we focused on the specific immune regulatory role of WFC in the treatment of CAG, especially on a hub pathway, Toll-like receptor signaling pathway and thus deciphered the role of WFC in immune regulation, anti-inflammation and mediation of HES6. In experiments part, MNNG-GES-1-cell line and rat models were used to validate our findings. RESULTS: In this study, compounds of WFC are identified through LC‒MS/MS and network target analysis is performed to dissect the specific immunoregulatory effect as well as mediation of HES6, a newly discovered biomolecule related to gastritis carcinoma progression, of WFC on CAG through the Toll-like receptor signaling pathway. Based on cell line and rat models, we verify the mechanism of action of WFC for CAG in inhibiting inflammatory cytokines, regulating immune cells like T cells and macrophages, related genes including TLR2 and CD14. It is also validated that WFC inhibits the expression of HES6 (P < 0.05). CONCLUSION: Based on the combination of computational strategy and experiments, our study offers a comprehensive analysis to reveal the role of WFC in regulating immune response, inhibiting inflammation in the treatment of CAG, and provides a standard example for the research of TCM from the perspective of the network and the system.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Ratos , Animais , Gastrite Atrófica/metabolismo , Cromatografia Líquida , Doença Crônica , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Receptores Toll-Like
12.
Front Immunol ; 13: 986785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059448

RESUMO

Recent studies have shown that tumor stemness has biological significance in tumorigenicity and tumor progression. However, the characteristics of TME immune infiltration in osteosarcoma mediated by the combined effects of multiple cancer stem cell-related genes remain unknown. Methods: In this study, we identified different cancer stem cell-associated subtypes in osteosarcoma based on 25 cancer stem cell-associated genes by consensus clustering analysis, and we comprehensively evaluated the association between these subtypes and immunocytes infiltration in the TME. The cancer stem cell (CSC) score was constructed to quantify the stemness of individual tumors. Results: We performed a comprehensive evaluation of 218 osteosarcoma patients based on 25 cancer stem cell-related genes. Three different cancer stem cells related subtypes were identified, which were related to different biological processes and clinical outcomes. The three subtypes have different TME cells infiltrating characteristics, and CSC Cluster A had a higher level of immunocyte infiltration compared to CSC Cluster B and C. We constructed a scoring system, called the CSC score, to assess the stemness of individual patients. Then we found that the prognosis of patients was predicted by CSC score, and patients with low CSC score had prolonged survival. Further analyses showed that low CSC score was correlated with enhanced immune infiltration. CSC score may predict the effect of immunotherapy, and patients with low CSC score may have better immune response and clinical prognosis. Conclusions: This study demonstrates that there could be three cancer stem cell-associated subtypes in osteosarcoma and that they were associated with different patient prognosis and TME immune infiltration characteristics. CSC score could be used to assess the stemness of individual patients, improve our comprehension of TME characteristics, and direct more effective immune therapy.


Assuntos
Fenômenos Biológicos , Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Humanos , Células-Tronco Neoplásicas/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , Prognóstico
13.
Comput Methods Programs Biomed ; 221: 106829, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35660765

RESUMO

BACKGROUND: Artificial intelligence (AI) analysis may serve as a scoring tool for programmed cell death ligand-1 (PD-L1) expression. In this study, a new AI-assisted scoring system for pathologists was tested for PD-L1 expression assessment in non-small cell lung cancer (NSCLC). METHODS: PD-L1 expression was evaluated using the tumor proportion score (TPS) categorized into three levels: negative (TPS < 1%), low expression (TPS 1-49%), and high expression (TPS ≥ 50%). In order to train, validate, and test the Aitrox AI segmentation model at the whole slide image (WSI) level, 54, 53, and 115 cases were used as training, validation, and test datasets, respectively. TPS reading results from five experienced pathologists, six inexperienced and the Aitrox AI model were analyzed on 115 PD-L1 stained WSIs. The Gold Standard for TPS was derived from the review of three expert pathologists. Spearman's correlation coefficient was calculated and compared between the results. RESULTS: Aitrox AI Model correlated strongly with the TPS Gold Standard and was comparable with the results of three of the five experienced pathologists. In contrast, the results of four of the six inexperienced pathologists correlated only moderately with the TPS Gold Standard. Aitrox AI Model performed better than the inexperienced pathologists and was comparable to experienced pathologists in both negative and low TPS groups. Despite the fact that the low TPS group showed 5.09% of cases with large fluctuations, the Aitrox AI Model still showed a higher correlation than the inexperienced pathologists. However, the AI model showed unsatisfactory performance in the high TPS groups, especially lower values than the Gold Standard in images with large regions of false-positive cells. CONCLUSION: The Aitrox AI Model demonstrates potential in assisting routine diagnosis of NSCLC by pathologists through scoring of PD-L1 expression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inteligência Artificial , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico
14.
Cancer Lett ; 536: 215660, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35318116

RESUMO

Despite recent improvements in the therapeutic management of osteosarcoma (OS), the ongoing challenges in overcoming resistance to tyrosine kinase inhibitors (TKIs) warrant new strategies to improve overall patient survival. In this study, we established four anlotinib-resistant OS cell lines and demonstrated that the mechanism of anlotinib resistance is due to the loss of PTEN and reactivation of the MAPK pathway. Reduced PTEN expression was also observed in tumor samples from patients with OS and lung metastasis. We investigated the effects of an orally active PI3K inhibitor, either alone or in combination with anlotinib, on the progression of resistant cells and a xenograft nude mouse model. Notably, PI3K inhibitor suppressed anlotinib-resistant OS cell proliferation, migration, invasion, and cytoskeleton formation, and induced apoptosis. Combined treatment with anlotinib augmented these effects by restoring PTEN expression and decreasing MAPK and PI3K/AKT/mTOR signaling. PI3K inhibitors could reverse anlotinib resistance in OS, limiting OS cell development in combination with anlotinib. Our findings rationalize further studies on the applications of PI3K inhibitors that can be clinically used in anlotinib-refractory OS management.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Osteossarcoma , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Indóis , Camundongos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas
15.
Adv Mater ; 34(19): e2200905, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35294781

RESUMO

Due to the adverse effects of erythropoietin (EPO) on cancer patient survival, it is necessary to develop new agents that can be used to efficiently manage and treat cancer-related anemia. In this study, novel distinctive carbon dots, J-CDs, derived from jujube are designed, synthesized, and characterized. Based on the obtained results, this material comprises sp2 and sp3 carbon atoms, as well as oxygen/nitrogen-based groups, and it specifically promotes the proliferation of erythroid cells by stimulating the self-renewal of erythroid progenitor cells in vitro and in vivo. Moreover, J-CDs have no discernible effects on tumor proliferation and metastasis, unlike EPO. Transcriptome profiling suggests that J-CDs upregulate the molecules involved in hypoxia response, and they also significantly increase the phosphorylation levels of STAT5, the major transducer of signals for erythroid progenitor cell proliferation. Overall, this study demonstrates that J-CDs effectively promote erythrocyte production without affecting tumor proliferation and metastasis; thus, they may be promising agents for the treatment of cancer-related anemia.


Assuntos
Anemia , Eritropoetina , Neoplasias , Anemia/tratamento farmacológico , Anemia/patologia , Carbono/farmacologia , Carbono/uso terapêutico , Células Precursoras Eritroides/patologia , Células Precursoras Eritroides/fisiologia , Eritropoese/fisiologia , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico
16.
Front Cell Dev Biol ; 9: 731311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692688

RESUMO

Background: Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM. Methods: Ninety-five osteosarcoma samples from the TARGET database were included. Iterative LASSO regression and multivariate Cox regression analysis were used to screen the IRLs signature with the optimal AUC. The predict function was used to calculate the risk score and divide osteosarcoma into a high-risk group and low-risk group based on the optimal cut-off value of the risk score. The lncRNAs in IRLs signature that affect metastasis were screened for in vitro validation. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were used to evaluate the role of TIM in the influence of IRLs on osteosarcoma prognosis. Results: Ten IRLs constituted the IRLs signature, with an AUC of 0.96. The recurrence and metastasis rates of osteosarcoma in the high-risk group were higher than those in the low-risk group. In vitro experiments showed that knockdown of lncRNA (AC006033.2) could increase the proliferation, migration, and invasion of osteosarcoma. ssGSEA and ESTIMATE results showed that the immune cell content and immune score in the low-risk group were generally higher than those in the high-risk group. In addition, the expression levels of immune escape-related genes were higher in the high-risk group. Conclusion: The IRLs signature is a reliable biomarker for the prognosis of osteosarcoma, and they alter the prognosis of osteosarcoma. In addition, IRLs signature and patient prognosis may be related to TIM in osteosarcoma. The higher the content of immune cells in the TIM of osteosarcoma, the lower the risk score of patients and the better the prognosis. The higher the expression of immune escape-related genes, the lower the risk score of patients and the better the prognosis.

17.
Mar Drugs ; 19(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564147

RESUMO

Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and ß are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRß provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRß, which we identified previously in edible marine seaweed Sargassum fusiforme. We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.


Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Hipolipemiantes/uso terapêutico , Sargassum , Estigmasterol/análogos & derivados , Animais , Aterosclerose/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Dieta Hiperlipídica , Hipolipemiantes/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas de Membrana Transportadoras/genética , Camundongos Knockout para ApoE , Estigmasterol/farmacologia , Estigmasterol/uso terapêutico
18.
ACS Omega ; 6(18): 12081-12098, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34056362

RESUMO

The Lucaogou Formation (Fm) in the Jimusaer depression is the first large-scale development of a terrigenous clastic sedimentary shale oil reservoir in China. Nearly one billion tons of shale oil resources have been discovered. However, the current exploration and development is concentrated in the eastern part of the sag. The limited geological understanding in the western area has restricted the prediction and development of "sweet spots" for shale oil. To help rectify this, we have studied the petrology, geochemistry, oil content, and pore properties of the second part of the first member (Mbr) of the Lucaogou Fm (P2l1 2) in a typical well (Ji-X) in the western part of the sag. The results show that P2l1 2 in the Jimusaer sag is a mixed fine-grained sedimentary system composed of sandstone, mudstone, and carbonate, which can be divided into seven types: dolomitic mudstone, calcareous mudstone, mudstone, mixed fine-grained rock, argillaceous limestone, sandstone, and argillaceous dolomite. The organic matter type of P2l1 2 in well Ji-X is dominated by types I and II, and this is the best source rock in the whole exploration area of the Jimusaer sag. The overall oil saturation is relatively high, but the maturity of crude oil is low, and the overall oil quality is heavy, which is mainly controlled by the sedimentary environment and maturity of source rocks. Lithology and reservoir physical properties are the key to control oil content. The high-quality light oil reservoir lithology is argillaceous dolomite and sandstone. The higher the content of macropores and mesopores, the weaker the heterogeneity of the pore structure, and the better the oil content in the reservoir. There are four light oil sweet spots in the upper part (burial depth less than 4366 m), and there are excellent source rocks with high HI and high organic matter content near each sweet spot. This discovery of shale oil enrichment regularity will effectively guide the development of shale oil in continental lacustrine basins in other parts of the world.

19.
J Environ Sci (China) ; 88: 90-102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862083

RESUMO

Sulfide-modified nanoscale zero-valent iron (S-nZVI) is a promising material for removal of organic pollutants from water, but S-nZVI nanoparticles (NPs) easily agglomerate and have poor contact with organic contaminants. Herein, we propose a new S-nZVI/graphene aerogel (S-nZVI/GA) composite which exhibits superior removal capability for trichloroethylene (TCE) from water. Three-dimensional porous graphene aerogel (GA) can improve the efficiency of electron transport, enhance the adsorption of organic pollutants and restrain the agglomeration of the core-shell S-nZVI NPs. The TCE removal rates of FeS, nZVI, GA and S-nZVI were 27.8%, 42%, 63% and 75% in 2 hr, respectively. Furthermore, TCE was completely removed within 50 min by S-nZVI/GA. The TCE removal rate increased with increasing pH and temperature, and TCE removal followed the pseudo-first-order kinetic model. The results demonstrate the great potential of S-nZVI/GA composite as a low-cost, easily separated and superior monolithic adsorbent for removal of organic pollutants.


Assuntos
Grafite , Água Subterrânea , Tricloroetileno , Poluentes Químicos da Água , Purificação da Água/métodos , Adsorção , Ferro , Sulfetos , Água
20.
Bioresour Technol ; 136: 730-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23558183

RESUMO

A conventional trickle bed reactor and its modified type both packed with Ca/Al composite oxide-based alkaline catalysts were studied for biodiesel production by transesterification of rapeseed oil and methanol. The effects of the methanol usage and oil flow rate on the FAME yield were investigated under the normal pressure and methanol boiling state. The oil flow rate had a significant effect on the FAME yield for the both reactors. The modified trickle bed reactor kept over 94.5% FAME yield under 0.6 mL/min oil flow rate and 91 mL catalyst bed volume, showing a much higher conversion and operational stability than the conventional type. With the modified trickle bed reactor, both transesterification and methanol separation could be performed simultaneously, and glycerin and methyl esters were separated additionally by gravity separation.


Assuntos
Álcalis/farmacologia , Alumínio/farmacologia , Biocombustíveis , Reatores Biológicos/microbiologia , Cálcio/farmacologia , Óxidos/farmacologia , Óleos de Plantas/metabolismo , Catálise/efeitos dos fármacos , Esterificação/efeitos dos fármacos , Ésteres/análise , Ácidos Graxos Monoinsaturados , Óleo de Brassica napus
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