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2.
Nanomedicine (Lond) ; : 1-20, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225560

RESUMO

Aim: We conducted a bibliometric analysis to quantitatively study the development pathway, research hotspots and evolutionary trends of nano-drug delivery systems (NDDS) in treating urological tumors.Materials & methods: We used the Web of Science Core Collection to retrieve the literature related to NDDS in the urological tumors up to November 1, 2023. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer and R-Bibliometrix. The major aspects of analysis included contributions from different countries/regions, authors' contributions, keywords identification, citation frequencies and overall research trends.Results: We included 3,220 articles. The analysis of annual publication trends revealed significant growth in this field since 2010, which has continued to the present day. The United States and China have far exceeded other countries/regions in the publication volume of papers in this field. The progression of the shell structure of NDDS in the urinary system has gradually transitioned from non-biological materials to biocompatible materials and ultimately to completely biocompatible materials. Mucoadhesive NDDS for intravesical drug delivery is a hotspot and a potential research material for bladder cancer.Conclusion: The field of NDDS in urological tumors has emerged as a research hotspot. Future research should focus on synergistic effects of NDDS with other treatment modalities.


[Box: see text].

3.
Clin Transl Oncol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325262

RESUMO

BACKGROUND: Full-dose BCG bladder perfusion therapy is effective, but there are serious side effects. Whether a low dose of BCG can reduce the side effects of treatment while maintaining its efficacy is still inconclusive. OBJECTIVE: To compare the efficacy of low-dose and full-dose BCG bladder perfusion therapy and to provide reference for individual treatment of bladder cancer. METHODS: All relevant literature published in PubMed, Web of Science, and Embrase databases up to April 2024 was searched. The results and shortcomings of the existing literature are analyzed, the cognitive gaps between different studies are pointed out, and suggestions are made for future research. RESULTS: A total of 32 pieces of literature were included. Twelve studies found that the efficacy of full-dose BCG perfusion was significantly better than that of low-dose BCG perfusion, and 20 studies found no statistical difference between low-dose and full-dose BCG perfusion CONCLUSION: Although there is no significant difference in the efficacy of full-dose and low-dose BCG in bladder perfusion, the trend indicates that the efficacy of full-dose BCG is still the most accurate. In cases where BCG resources are scarce or patients are intolerant, low-dose BCG bladder perfusion therapy may be an alternative to full-dose BCG bladder perfusion therapy. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

4.
Clin Transl Oncol ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266874

RESUMO

BACKGROUND: It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue. OBJECTIVE: To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients. METHODS: A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research. RESULTS: A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients. CONCLUSIONS: Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

5.
Bioorg Chem ; 153: 107802, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244972

RESUMO

The treatment of bladder cancer is limited by low drug efficacy and drug resistance. Hence, this study aimed to screen and identify potential drug precursors and investigate their mechanism of action. A set of camptothecin derivatives showing high anti-tumor potential was selected from early-stage research or literature and synthesized to construct a compound library. A total of 135 compounds were screened in T24 and J82 cells, revealing that FL118 significantly inhibited the proliferation of GC (gemcitabine + cisplatin)-sensitive/insensitive cells. FL118 exhibited excellent penetration and killing ability in organoids and three GC-insensitive patient-derived xenografts. Chemical proteomic and docking calculations were employed to identify binding proteins, indicating that FL118 can bind into H2A.X and its entwined DNA. The results of Cellular thermal shift assay and surface plasmon resonance (Kd = 3.77E-6) support the above findings. Fluorescence localization revealed widespread binding of FL118 within the cell nucleus. Furthermore, WB showed that FL118 increased cellular DNA damage, resulting in significant cell cycle inhibition. The binding of FL118 to H2A.X hindered the damage repair process, leading to apoptosis. Controllable adverse reactions were observed in mice treated with FL118. In conclusion, FL118 may be a superior anti-bladder cancer compound that acts as a molecular glue binding to both H2A.X and DNA. The resistance mediated by the DNA damage repair to DNA damage caused by GC regimen can be reversed by FL118. This distinct mechanism of FL118 has the potential to complement existing mainstream treatment approaches for bladder cancer.

6.
Medicine (Baltimore) ; 103(34): e39384, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39183406

RESUMO

Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.


Assuntos
Astenozoospermia , Disfunção Erétil , Simulação de Acoplamento Molecular , Farmacologia em Rede , Panax , Masculino , Humanos , Panax/química , Disfunção Erétil/tratamento farmacológico , Astenozoospermia/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Mapas de Interação de Proteínas , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Sitosteroides/farmacologia
7.
ACS Synth Biol ; 13(8): 2533-2544, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39090815

RESUMO

ß-ionone, a norisoprenoid, is a natural aromatic compound derived from plants, which displays various biological activities including anticancer, antioxidant and deworming properties. Due to its large biomass and strong environmental tolerance, the nonconventional oleaginous yeast Candida tropicalis was selected to efficiently synthesize ß-ionone. We initially investigated the capacity of the cytoplasm and subcellular compartments to synthesize ß-ionone independently. Subsequently, through adaptive screening of enzymes, functional identification of subcellular localization signal peptides and subcellular compartment combination strategies, a titer of 152.4 mg/L of ß-ionone was achieved. Finally, directed evolution of rate-limiting enzyme and overexpression of key enzymes were performed to enhance ß-ionone production. The resulting titer was 400.5 mg/L in shake flasks and 730 mg/L in a bioreactor. This study demonstrates the first de novo synthesis of ß-ionone in C. tropicalis, providing a novel cellular chassis for terpenoid fragrances with considerable industrial potential.


Assuntos
Candida tropicalis , Engenharia Metabólica , Norisoprenoides , Candida tropicalis/metabolismo , Candida tropicalis/genética , Engenharia Metabólica/métodos , Norisoprenoides/metabolismo , Reatores Biológicos
8.
Cardiorenal Med ; 14(1): 307-319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38740015

RESUMO

INTRODUCTION: Cardiorenal syndrome encompasses a range of disorders involving both the heart and kidneys, wherein dysfunction in one organ may induce dysfunction in the other, either acutely or chronically. METHODS: This study conducted a literature search on cardiorenal syndrome from January 1, 2003, to September 8, 2023. Meanwhile, a quantitative analysis of the developmental trajectory, research hotspots and evolutionary trends in the field of cardiorenal syndrome through bibliometric analysis and knowledge mapping was carried out. RESULTS: The annual publication trend analysis revealed a consistent annual increase in cardiorenal syndrome literature over the last 20 years. The IL6, REN, and INS genes were identified as the current research hotspots. CONCLUSION: The field of cardiorenal syndrome exhibits promising potential to grow and is emerging as a prominent research area. Future endeavours should prioritise a comprehensive understanding of the field and foster multi-centre co-operation among different countries and regions.


Assuntos
Bibliometria , Síndrome Cardiorrenal , Síndrome Cardiorrenal/fisiopatologia , Humanos , Pesquisa Biomédica/tendências
9.
Angew Chem Int Ed Engl ; 63(20): e202402642, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38453641

RESUMO

Conjugated polymers (CPs) with low crystallinity are promising candidates for application in organic thermoelectrics (OTEs), particularly in flexible devices, because the disordered structures of these CPs can effectively accommodate dopants and ensure robust resistance to bending. However, n-doped CPs usually exhibit poor thermoelectric performance, which hinders the development of high-performance thermoelectric generators. Herein, we report an n-type CP (ThDPP-CNBTz) comprising two acceptor units: a thiophene-flanked diketopyrrolopyrrole and a cyano-functionalized benzothiadiazole. ThDPP-CNBTz shows a low LUMO energy level of below -4.20 eV and features low crystallinity, enabling high doping efficiency. Moreover, the dual-acceptor design enhances polaron delocalization, resulting in good thermoelectric performance. After n-doping, ThDPP-CNBTz exhibits an average electrical conductivity (σ) of 50.6 S cm-1 and a maximum power factor (PF) of 126.8 µW m-1 K-2, which is among the highest values reported for solution-processed n-type CPs to date. Additionally, a solution-processed flexible OTE device based on doped ThDPP-CNBTz exhibits a maximum PF of 70 µW m-1 K-2; the flexible device also shows remarkable resistance to bending strain, with only a marginal change in σ after 600 bending cycles. The findings presented in this work will advance the development of n-type CPs for OTE devices, and flexible devices in particular.

10.
Urol Oncol ; 42(5): 144-154, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38485644

RESUMO

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Adenocarcinoma/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Proliferação de Células
11.
Sci Rep ; 14(1): 4667, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409247

RESUMO

This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.


Assuntos
Transtorno da Personalidade Antissocial , Personalidade , Humanos , Maquiavelismo , Transtornos da Personalidade , Narcisismo , Ansiedade
12.
Macromol Rapid Commun ; 45(1): e2300245, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37278130

RESUMO

A series of thienoisoindigo (TIG)-based conjugated polymers (CPs) with high molecular weights are synthesized by direct arylation polycondensation (DArP) by using TIG derivatives as CBr monomer and multi-halogenated thiophene derivatives, i.e., (E)-1,2-bis(3,4-difluorothien-2-yl)ethene (4FTVT), (E)-1,2-bis(3,4-dichlorothien-2-yl)ethene (4ClTVT), 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT), and 3,3',4,4'-tetrachloro-2,2'-bithiophene (4ClBT), as CH monomers. Density functional theory (DFT) calculations reveal the high selectivity between α-CH bonds in 4FTVT, 4ClTVT, 4FBT, and 4ClBT and ß-CH bonds in TIG CBr monomer. All four resulting CPs exhibit low optical bandgaps of ca. 1.20 eV and ambipolar transport characteristics with both electron and hole mobility above 0.1 cm2  V-1  s-1 as elaborated with organic thin-film transistors (OTFTs). The polymer TIG-4FTVT delivers the best device performance. With this polymer, n-channel OTFTs with electron mobility up to 1.67 cm2  V-1  s-1 and p-channel OTFTs with hole mobility up to 0.62 cm2  V-1  s-1 are fabricated by modifying source/drain electrodes with polyethylenimine ethoxylated (PEIE) and MoO3 , respectively, to selectively inject electrons and holes.


Assuntos
Etilenos , Polímeros , Polímeros/química , Tiofenos/química , Elétrons
13.
Int J Mol Sci ; 24(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37569764

RESUMO

Cyanobacterial harmful algal blooms (CyanoHABs) pose significant threats to human health and natural ecosystems worldwide, primarily caused by water eutrophication, increased surface water temperature, and co-occurring microorganisms. Urgent action is needed to develop an eco-friendly solution to effectively curb the proliferation of CyanoHABs. Sophorolipids (SLs) are fully biodegradable biosurfactants synthesized by Starmerella bombicola. They can be classified into lactone and acid types. The lactone type displays strong antimicrobial activity, while the acid type exhibits good solubility, which make them ideal agents for mitigating CyanoHABs. Nevertheless, the broad utilization of SLs are hindered by their expensive production costs and the absence of effective genetic editing tools in the native host. In this study, we constructed recombinant strains capable of producing either acidic or lactonic SLs using the CRISPR-Cas9 gene editing system. The yields of acidic and lactonic SLs reached 53.64 g/L and 45.32 g/L in a shaking flask, respectively. In a 5 L fermenter, acidic SLs reached 129.7 g/L using low-cost glucose and rapeseed oil as substrates. The addition of 5 mg/L lactonic SLs effectively degraded cyanobacteria within 30 min, and a ratio of 8.25:1.75 of lactonic to acidic SLs showed the highest degradation efficiency. This study offers a safe and promising solution for CyanoHABs treatment.


Assuntos
Cianobactérias , Proliferação Nociva de Algas , Humanos , Ecossistema , Cianobactérias/genética , Lactonas
14.
Macromol Rapid Commun ; 44(23): e2300393, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37640284

RESUMO

3,4-Difluorothiophene-substituted aryls, i.e., 1,4-bis(3,4-difluorothiophen-2-yl)-benzene (Ph-2FTh), 1,4-bis(3,4-difluorothiophen-2-yl)-2,5-difluorobenzene (2FPh-2FTh), and 4,7-bis(3,4-difluorothiophen-2-yl)-2,1,3-benzothiadiazole (BTz-2FTh), are synthesized as C─H monomers for the synthesis of conjugated polymers (CPs) via direct arylation polycondensation (DArP) with diketopyrrolopyrrole (DPP) and isoindigo (IID) derivatives as C─Br monomers. The Gibbs free energies of activation for direct arylation (ΔG298 K , kcal mol-1 ) for α─C─H bonds of thiophene moieties as calculated by density functional theory (DFT) are 14.3, 16.5, and 16.4 kcal mol-1 for Ph-2FTh, 2FPh-2FTh and BTz-2FTh, respectively, meaning that inserting an electron-deficient unit in 3,3',4,4'-tetrafluoro-2,2'-bithiophene (4FBT, ΔG298K : 14.6 kcal mol-1 ) may cause a reactivity decrease of the C─H monomers. Photophysical and semiconducting properties of the resulting six CPs (i.e., DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz) are characterized in detail. DPP-based CPs show ambipolar transport properties while IID-based ones exhibited n-type behavior owing to the deeper frontier molecular orbital energy levels of IID-based CPs. With source/drain electrodes modified with polyethylenimine ethoxylated, n-channel organic thin-film transistors with maximum electron mobility of 0.40, 0.54, 0.29, 0.05, 0.16, and 0.01 cm2 V-1 s-1 for DPP-Ph, DPP-2FPh, DPP-BTz, 2FIID-Ph, 2FIID-2FPh, and 2FIID-BTz, respectively, are fabricated. DPP-2FPh exhibits the best device performance due to the good film morphology and the highest intermolecular packing order.


Assuntos
Polímeros , Pirróis , Gravidez , Humanos , Feminino , Polímeros/química , Pirróis/química , Cetonas , Tiofenos/química
15.
Angew Chem Int Ed Engl ; 62(20): e202219262, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-36917081

RESUMO

n-Type conjugated polymers (CPs) are crucial in the applications of organic electronics. Direct coupling of electron-deficient C-H monomer via selective C-H activation, namely C-H/C-H oxidative direct arylation polycondensation (Oxi-DArP), is an ideal approach toward such CPs. Herein, Oxi-DArP is firstly adopted to synthesize a high-performance n-type CP using a newly developed monomer, i.e., 3,6-di(thiazol-5-yl)-diketopyrrolopyrrole (Tz-5-DPP). Tz-5-DPP based homopolymer PTz-5-DPP with a molecular weight of 22 kDa has been synthesized via Oxi-DArP. After n-doping, PTz-5-DPP films exhibited electric conductivity values up to 8 S cm-1 and power factors (PFs) up to 106 µW m-1 K-2 . Notably, this PF value is the highest for n-type polymer thermoelectric materials to date. The Oxi-DArP synthesis and the excellent n-type performance of the polymer make this work an important step toward the straightforward and sustainable preparation of high-performance n-type polymer semiconductors.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36361460

RESUMO

Negative emotions caused by break-up are the key work of university students' psychological intervention. It is important to explore the specific factors of break-up distress for university students' psychological intervention. Therefore, we investigated 869 university students to examine the effect of Machiavellianism and psychological capital on break-up distress, as well as its gender difference. The results indicated that high Machiavellians experience more break-up distress. Moreover, through structural equation models, we found that as for female university students, psychological capital mediated the relationship between Machiavellianism and break-up distress. However, as for male university students, the mediation effect was not significant. It means that for female university students, psychological capital acted as the mechanism to connect Machiavellianism and break-up distress.


Assuntos
Maquiavelismo , Angústia Psicológica , Feminino , Humanos , Masculino
17.
ACS Synth Biol ; 11(4): 1497-1509, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35294186

RESUMO

Gene editing technology plays an extremely significant role in synthetic biology and metabolic engineering. Traditional genetic manipulation methods, such as homologous recombination, however, are inefficient, time-consuming, and barely feasible when disrupting multiple genes simultaneously. Starmerella bombicola, a nonconventional yeast that overproduces sophorolipids, lacks convenient genetic tools for engineering strains. Here, we developed an efficient CRISPR-Cas9 genome editing technology by combining molecular element mining and expression system optimization for S. bombicola. This CRISPR-Cas9 system improved the efficiency of gene-integration/target gene-introducing disruption by homology-directed repair and realized the multi-gene simultaneous disruptions. Based on this CRISPR-Cas9 system, we also further constructed an engineered strain via the in vivo assembly of multiple DNA fragments (10 kb) that can produce acid-type sophorolipids. These results showed that the CRISPR-Cas9 system may be an efficient and convenient strategy to perform genetic manipulation in S. bombicola.


Assuntos
Sistemas CRISPR-Cas , Saccharomycetales , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Saccharomycetales/genética , Leveduras/genética
18.
Cell Cycle ; 20(23): 2531-2546, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34724861

RESUMO

Exosomes mediate the interaction between cancer cells and their microenvironment, and play a key role in tumor development. Although exosomes can package lncRNAs to mediate extracellular communication, the role of exosomal lncRNA AY927529 in prostate cancer (PCa) remains unclear. Exosomes were extracted from normal human prostatic epithelial cell lines (BPH-1 and RWPE-1) and PCa cell lines (VCaP and LNCaP, DU145, PC3) by ultrahigh speed centrifugation. Results of Western blot indicated that Alix, HSC70 and TSGl01 protein levels were upregulated in exosomes derived from PCa cells. LncAY927529 level was upregulated in PCa cells and exosomes derived from PCa patient serum and human PCa cells. CCK-8, Transwell and Flow cytometry assays demonstrated that bone marrow stromal cell line (ST2) conditioned medium (ST2-CM), treated with exosomes derived from PCa cells with high lncAY927529 level, promoted proliferation and invasion of PC3 and DU145 cells, and inhibited cell apoptosis. RT-qPCR assay indicated that lncAY927529 level was downregulated in PC3 and DU145 cells, exosomes derived from PCa cells (PCa-Exo) and ST2-CM treated with PCa-Exo with low expression of lncAY927529, and overexpression of lncAY927529 had the opposite results. In addition, Western blot assay showed that the autophagy related protein LC3II level was increased in ST2 cells treated with exosomes derived from DU145 cells with high expression of lncAY927529, and LC3I protein level was decreased. CXCL14 acted as a RNA-binding protein of lncAY927529, and exosome-mediated lncAY927529 positively regulated CXCL14 levels in ST2 cells. In general, exosome-mediated lncAY927529 could promote PCa cell proliferation and invasion by regulating bone microenvironment, suggesting that exosomal lncAY927529 may be a potential molecular diagnostic marker of PCa.


Assuntos
Exossomos , MicroRNAs , Hiperplasia Prostática , Neoplasias da Próstata , RNA Longo não Codificante , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Exossomos/genética , Exossomos/metabolismo , Humanos , Masculino , MicroRNAs/genética , Próstata , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética
19.
BMC Cancer ; 21(1): 1022, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525951

RESUMO

BACKGROUND: Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study. METHODS: In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR (qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo. RESULTS: Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells. CONCLUSION: eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.


Assuntos
Antígeno B7-H1/metabolismo , Fatores de Iniciação em Eucariotos/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Apoptose/genética , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fatores de Iniciação em Eucariotos/genética , Citometria de Fluxo , Inativação Gênica , Genes p53/fisiologia , Humanos , Imunoprecipitação , L-Lactato Desidrogenase/metabolismo , Leucócitos Mononucleares/imunologia , Linfócitos do Interstício Tumoral , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transfecção/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
ACS Macro Lett ; 10(4): 419-425, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35549230

RESUMO

Direct arylation of 2,7-dibromofluorene with n-octyl, 6-diethoxylphosphorylhexyl, 6-(N,N-diethylamino)hexyl or 6-bromohexyl side chains and 1,2,4,5-tetrafluorobenzene (TFB) were conducted to investigate the effect of side chain functional groups on the coupling, and the resulting TFB-substituted fluorene derivatives were used as C-H monomers for the synthesis of water/alcohol soluble conjugated polymers (WSCPs) by direct arylation polycondensation (DArP). The direct arylation and DArP of the monomers carrying phosphonate and amino groups went on smoothly in typical DArP conditions, that is, Pd(OAc)2/PtBu2Me-HBF4/base/DMAc and Pd2(dba)3·CHCl3/P(o-MeOPh)3/pivalic acid/base/THF, and high molecular weight polymers with these groups were successfully synthesized. However, for fluorene-monomers with bromohexyl side chains, the target products could not be obtained from the above conditions but could be prepared in the absence of carboxylic acid additives in low polar solvents. With the above DArP-made polymers as cathode interfacial layers, high performance organic solar cells (OSCs) were successfully fabricated.

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