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1.
Hum Mol Genet ; 33(6): 478-490, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-37971354

RESUMO

BACKGROUND: Colorectal cancer (CRC) is impacted by various environmental and genetic variables. Dysregulation of vesicle-mediated transport-related genes (VMTRGs) has been observed in many malignancies, but their effect on prognosis in CRC remains unclear. METHODS: CRC samples were clustered into varying subtypes per differential expression of VMTRGs. R package was utilized to explore differences in survival, immune, and drug sensitivity among different disease subtypes. According to differentially expressed genes (DEGs) between subtypes, regression analysis was employed to build a riskscore model and identify independent prognostic factors. The model was validated through a Gene Expression Omnibus (GEO) dataset. Immune landscape, immunophenoscore (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) scores for different risk groups were calculated. RESULTS: Two subtypes of CRC were identified based on VMTRGs, which showed significant differences in survival rates, immune cell infiltration abundance, immune functional activation levels, and immune checkpoint expression levels. Cluster2 exhibited higher sensitivity to anti-tumor drugs such as Nilotinib, Cisplatin, and Oxaliplatin compared to Cluster1. DEGs were mainly enriched in biological processes such as epidermis development, epidermal cell differentiation, and receptor-ligand activity, and signaling pathways like pancreatic secretion. The constructed 13-gene riskscore model demonstrated good predictive ability for CRC patients' prognosis. Furthermore, differences in immune landscape, IPS, and TIDE scores were observed among different risk groups. CONCLUSION: This study successfully obtained two CRC subtypes with distinct survival statuses and immune levels based on differential expression of VMTRGs. A 13-gene risk model was constructed. The findings had important implications for prognosis and treatment of CRC.


Assuntos
Neoplasias Colorretais , Humanos , Prognóstico , Transporte Biológico , Oxaliplatina , Neoplasias Colorretais/genética
2.
J Biol Chem ; 299(6): 104787, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149147

RESUMO

Understanding the functional properties of severe acute respiratory syndrome coronavirus 2 nonstructural proteins is essential for defining their roles in the viral life cycle, developing improved therapeutics and diagnostics, and countering future variants. Coronavirus nonstructural protein Nsp15 is a hexameric U-specific endonuclease whose functions, substrate specificity, mechanism, and dynamics are not fully defined. Previous studies report that Nsp15 requires Mn2+ ions for optimal activity; however, the effects of divalent ions on Nsp15 reaction kinetics have not been investigated in detail. Here, we analyzed the single- and multiple-turnover kinetics for model ssRNA substrates. Our data confirm that divalent ions are dispensable for catalysis and show that Mn2+ activates Nsp15 cleavage of two different ssRNA oligonucleotide substrates but not a dinucleotide. Biphasic kinetics of ssRNA substrates demonstrates that Mn2+ stabilizes alternative enzyme states that have faster substrate cleavage on the enzyme. However, we did not detect Mn2+-induced conformational changes using CD and fluorescence spectroscopy. The pH-rate profiles in the presence and absence of Mn2+ reveal active-site ionizable groups with similar pKas of ca. 4.8 to 5.2. An Rp stereoisomer phosphorothioate modification at the scissile phosphate had minimal effect on catalysis supporting a mechanism involving an anionic transition state. However, the Sp stereoisomer is inactive because of weak binding, consistent with models that position the nonbridging phosphoryl oxygen deep in the active site. Together, these data demonstrate that Nsp15 employs a conventional acid-base catalytic mechanism passing through an anionic transition state, and that divalent ion activation is substrate dependent.


Assuntos
Endonucleases , Íons , Clivagem do RNA , SARS-CoV-2 , Catálise , COVID-19/microbiologia , Endonucleases/genética , Endonucleases/metabolismo , Cinética , Metais/química , Clivagem do RNA/genética , SARS-CoV-2/enzimologia , Íons/metabolismo , Ativação Enzimática , Manganês/química , Concentração de Íons de Hidrogênio , Animais , Camundongos , Escherichia coli/genética
3.
Neoplasma ; 71(2): 180-192, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38766853

RESUMO

It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study, CALR and EIF2AK2 expression was measured in the clinical specimens of 39 patients with melanoma. Then, we constructed knockdown and overexpression cell models of CALR and EIF2AK2 and used wound healing and Transwell assays to observe cell migration and invasion. Apoptosis, EDU, and ROS assays were used to measure cell apoptosis and proliferation, as well as ROS levels. The effect of CALR on endoplasmic reticulum stress was detected using endoplasmic reticulum fluorescent probes. Western blotting was used to detect protein levels of CALR, EIF2AK2, ADAR1, and MMP14. The results indicated that CALR and EIF2AK2 expression levels were significantly higher in human melanoma tissues than in adjacent non-tumor tissue. In addition, we found a correlation between CALR and the expression of EIF2AK2 and MMP14, and the experimental results indicated that overexpression of CALR significantly upregulated the expression of EIF2AK2, MMP14, and ADAR1, while knockdown of CALR inhibited their expression. Notably, the knockdown of EIF2AK2 in the CALR overexpression group blocked the upregulation of MMP14 and ADAR1 expression by CALR, and the knockdown of both CALR and EIF2AK2 significantly inhibited MMP14 and ADAR1 expression. In conclusion, CALR and EIF2AK2 play a promoting role in melanoma progression, and knockdown of CALR and EIF2AK2 may be an effective anti-tumor target, and its mechanism may be through MMP14, ADAR1 signaling.


Assuntos
Adenosina Desaminase , Calreticulina , Proliferação de Células , Metaloproteinase 14 da Matriz , Melanoma , Proteínas de Ligação a RNA , Transdução de Sinais , eIF-2 Quinase , Humanos , Adenosina Desaminase/metabolismo , Adenosina Desaminase/genética , Melanoma/patologia , Melanoma/metabolismo , Melanoma/genética , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Calreticulina/genética , Calreticulina/metabolismo , Linhagem Celular Tumoral , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/genética , Movimento Celular , Apoptose , Estresse do Retículo Endoplasmático , Feminino , Progressão da Doença , Masculino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade
4.
Small ; 19(14): e2206174, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36651135

RESUMO

Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.


Assuntos
Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Paclitaxel/farmacologia , Neoplasias/terapia , Sistemas de Liberação de Medicamentos/métodos , Resistência a Múltiplos Medicamentos , Metais , Linhagem Celular Tumoral , Microambiente Tumoral
5.
J Chem Phys ; 159(4)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37486048

RESUMO

In this work, we develop an accurate and efficient XGBoost machine learning model for predicting the global-density-dependent range-separation parameter, ωGDD, for long-range corrected functional (LRC)-ωPBE. This ωGDDML model has been built using a wide range of systems (11 466 complexes, ten different elements, and up to 139 heavy atoms) with fingerprints for the local atomic environment and histograms of distances for the long-range atomic correlation for mapping the quantum mechanical range-separation values. The promising performance on the testing set with 7046 complexes shows a mean absolute error of 0.001 117 a0-1 and only five systems (0.07%) with an absolute error larger than 0.01 a0-1, which indicates the good transferability of our ωGDDML model. In addition, the only required input to obtain ωGDDML is the Cartesian coordinates without electronic structure calculations, thereby enabling rapid predictions. LRC-ωPBE(ωGDDML) is used to predict polarizabilities for a series of oligomers, where polarizabilities are sensitive to the asymptotic density decay and are crucial in a variety of applications, including the calculations of dispersion corrections and refractive index, and surpasses the performance of all other popular density functionals except for the non-tuned LRC-ωPBE. Finally, LRC-ωPBE (ωGDDML) combined with (extended) symmetry-adapted perturbation theory is used in calculating noncovalent interactions to further show that the traditional ab initio system-specific tuning procedure can be bypassed. The present study not only provides an accurate and efficient way to determine the range-separation parameter for LRC-ωPBE but also shows the synergistic benefits of fusing the power of physically inspired density functional LRC-ωPBE and the data-driven ωGDDML model.

6.
J Nanobiotechnology ; 21(1): 146, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143039

RESUMO

BACKGROUND: Uveal melanoma (UM) is adults' most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients' vision. METHODS AND RESULTS: Herein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety. CONCLUSION: This noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM.


Assuntos
Melanoma , Nanopartículas , Fotoquimioterapia , Porfirinas , Humanos , Compostos Férricos , Linhagem Celular Tumoral , Fototerapia/métodos , Melanoma/diagnóstico por imagem , Melanoma/terapia , Porfirinas/uso terapêutico , Porfirinas/farmacologia , Nanopartículas/uso terapêutico
7.
Sensors (Basel) ; 23(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447884

RESUMO

Damage is the main form of conflict, and the characterization of damage information is an important component of conflict evaluation. In the existing research, damage mainly refers to the damage effect of a damage load on the target structure. However, in the actual conflict environment, damage is a complex process that includes the entire process from the initial introduction of the damage load to the target function. Therefore, in this paper, the transfer logic of the damage process is analyzed, and the damage process is sequentially divided into being discovered, being attacked, being hit, and being destroyed in succession. Specifically, first considering the multiple types of each process, the transmission of damage is likened to the flow of damage, a network model to characterize damage information based on heterogeneous network meta-path and network flow theory (HF-MCDI) is established. Then, the characteristics of damage information are analyzed based on the capacity of the damage network, the correlation of the damage path, and the importance of the damage node. In addition, HF-MCDI can not only represent the complete damage information and the transmission characteristics of the damage load but also the structural characteristics of the target. Finally, the feasibility and effectiveness of the established HF-MCDI method are fully demonstrated by the example analysis of the launch platform.

8.
World J Microbiol Biotechnol ; 39(5): 125, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36941474

RESUMO

In recent years, the development of green energy to replace fossil fuels has been the focus of research. Higher alcohols are important biofuels and chemicals. The production of higher alcohols in microbes has gained attention due to its environmentally friendly character. Higher alcohols have been synthesized in model microorganism Escherichia coli, and the production has reached the gram level through enhancement of metabolic flow, the balance of reducing power and the optimization of fermentation processes. Sustainable bio-higher alcohols production is expected to replace fossil fuels as a green and renewable energy source. Therefore, this review summarizes the latest developments in producing higher alcohols (C3-C6) by E. coli, elucidate the main bottlenecks limiting the biosynthesis of higher alcohols, and proposes potential engineering strategies of improving the production of biological higher alcohols. This review would provide a theoretical basis for further research on higher alcohols production by E. coli.


Assuntos
Álcoois , Escherichia coli , Álcoois/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica , Biocombustíveis , Fermentação
9.
Zhongguo Zhong Yao Za Zhi ; 48(24): 6682-6692, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38212028

RESUMO

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.


Assuntos
Fibrose Pulmonar , Camundongos , Masculino , Animais , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/genética , Fibrose Pulmonar/induzido quimicamente , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fibronectinas/metabolismo , Vimentina/metabolismo , Cromatografia Líquida , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Estresse Oxidativo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , RNA Mensageiro/metabolismo
10.
Angew Chem Int Ed Engl ; 62(4): e202209306, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36395246

RESUMO

Covalent organic framework nanosheets (COF-NSs) are emerging building blocks for functional materials, and their scalable fabrication is highly desirable. Current synthetic methods suffer from low volume yields resulting from confined on-surface/at-interface growth space and complex multiple-phase synthesis systems. Herein, we report the synthesis of charged COF-NSs in open space using a single-phase organic solution system, achieving magnitudes higher volume yields of up to 18.7 mg mL-1 . Charge-induced electrostatic repulsion forces enable in-plane anisotropic secondary growth from initial discrete and disordered polymers into large and crystalline COF-NSs. The charged COF-NS colloidal suspensions are cast into thin and compact proton exchange membranes (PEMs) with lamellar morphology and oriented crystallinity, displaying outstanding proton conductivity, negligible dimensional swelling, and good H2 /O2 fuel cell performance.

11.
Dig Dis Sci ; 67(6): 2182-2194, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34021424

RESUMO

BACKGROUND: Fucosylation alteration is involved in several steps of human cancer pathogenesis. Dysregulated long non-coding RNA (lncRNA) often leads to malignancy in colorectal cancer (CRC). METHODS: Differential levels of LEF1-AS1, LEF1 and FUT8 are analyzed by qRT-PCR and western blot. Chip, RIP, EMSA and luciferase reporter assay confirm the direct interaction among LEF1-AS1, MLL1, H3K4me3, LEF1 and FUT8. Functionally, CRC cell proliferation, migration and invasion are analyzed by CCK8 assay, colony formation assay, transwell assay and flow cytometry. The xenografts nude mice models, lung metastasis and liver metastasis are established to determine the effect of LEF1-AS1/LEF1/FUT8 axis on CRC progression in vivo. RESULTS: Here, we identify that LEF1-AS1 and LEF1 are higher in CRC tissues than that in adjacent tissues, as well as upregulated in CRC cell lines than that in normal colorectal cells. Altered levels of LEF1-AS1 modulate LEF1 expression, while altered LEF1 could not regulate LEF1-AS1. LEF1-AS1 recruits MLL1 to the promoter region of LEF1, induces H3K4me3 methylation modification and mediates LEF1 transcription. Furthermore, α1-6 fucosyltransferase FUT8 is overexpressed in CRC tissues and positively correlated to LEF1. FUT8 is a direct target of transcription factor LEF1, which regulates FUT8 level. Altered FUT8 also regulates the core fucosylation of CRC cells, and LEF1-AS1 mediates FUT8 level through activation of Wnt/ß-catenin/LEF1 pathway, thereby resulting in ß-catenin nuclear translocation. In addition, LEF1-AS1 mediates the proliferation, migration and invasion of CRC cells in vitro. LEF1-AS1 silence hinders the tumorigenesis, liver and lung metastasis of SW620 cells in vivo, while overexpressed FUT8 abolishes the suppressive impact of LEF1-AS1 repression on the biological behavior of SW620 cells. CONCLUSION: Our studies uncovered a novel mechanism for constitutive LEF1-AS1/LEF1/FUT8 axis in CRC progression by regulating α1, 6-fucosylation via Wnt/ß-catenin pathway, and consequently, as a potential therapeutic target in CRC.


Assuntos
Neoplasias Colorretais , Fucosiltransferases , Neoplasias Pulmonares , Fator 1 de Ligação ao Facilitador Linfoide , RNA Longo não Codificante , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Camundongos , Camundongos Nus , RNA Antissenso/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
12.
Bioorg Chem ; 109: 104711, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33609916

RESUMO

In this study, a series of novel 2H-imidazo [1, 2-c] pyrazolo [3, 4-e] pyrimidine derivatives were designed, synthesized, and evaluated for their cytotoxic activities. The in vitro cell growth inhibition assay of the target compounds indicated their selectivity in inhibiting the proliferation of blood tumor cells (K562, U937) and solid tumor cells (HCT116, HT-29). Compound 9b exhibited the highest antiproliferative activities against K562 (IC50 = 5.597 µM) and U937 (IC50 = 3.512 µM). Based on the flow cytometry assays, compound 9b caused obvious induction of cell apoptosis and cell arrest at the S phase. Furthermore, western blot analysis revealed that compound 9b upregulated the expression of Bax, downregulated the levels of Bcl-2, and further activated caspase-3 in K562 cells. Therefore, compound 9b may be a potential anticancer agent that deserves further investigation.


Assuntos
Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Pirimidinas/síntese química , Pirimidinas/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Células K562 , Pirimidinas/química , Células U937
13.
BMC Pulm Med ; 21(1): 347, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742261

RESUMO

BACKGROUND: We have reported that heparin-binding epidermal growth factor (HB-EGF) is increased in patients with chronic obstructive pulmonary disease (COPD) and associated with collagen deposition, but the mechanisms remain unclear. In the present study, we aimed to investigated the inflammatory cytokines secreted by bronchial epithelial cells following exposure to HB-EGF that promoted proliferation and migration of human lung fibroblast. METHODS: HB-EGF-induced inflammatory cytokines were assayed in two airway epithelial cells (primary human bronchial epithelial cells [HBECs] and BEAS-2B cells). Moreover, the culture supernatants derived from HB-EGF-treated HBECs and BEAS-2B cells were added to human primary lung fibroblasts. The effect of culture supernatants on proliferation and migration of fibroblasts was assessed. RESULTS: IL-8 expression was significantly increased in bronchial epithelial cells treated with HB-EGF, which was at least partially dependent on NF-kB pathways activation. HB-EGF-induced IL-8 was found to further promote lung fibroblasts proliferation and migration, and the effects were attenuated after neutralizing IL-8. CONCLUSIONS: These findings suggest that HB-EGF may be involved in the pathology of airway fibrosis by induction of IL-8 from airway epithelium, subsequently causing lung fibroblasts proliferation and migration. Thus, inhibition of HBEGF and/or IL-8 production could prevent the development of airway fibrosis by modulating fibroblast activation.


Assuntos
Epitélio/metabolismo , Fibroblastos/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Interleucina-8/metabolismo , Pulmão/metabolismo , Técnicas de Cultura de Células , Proliferação de Células , Fibroblastos/patologia , Fibrose/patologia , Humanos , Pulmão/fisiopatologia
14.
Angew Chem Int Ed Engl ; 60(5): 2221-2231, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32282107

RESUMO

The advent of SELEX (systematic evolution of ligands by exponential enrichment) technology has shown the ability to evolve artificial ligands with affinity and specificity able to meet growing clinical demand for probes that can, for example, distinguish between the target leukemia cells and other cancer cells within the matrix of heterogeneity, which characterizes cancer cells. Though antibodies are the conventional and ideal choice as a molecular recognition tool for many applications, aptamers complement the use of antibodies due to many unique advantages, such as small size, low cost, and facile chemical modification. This Minireview will focus on the novel applications of aptamers and SELEX, as well as opportunities to develop molecular tools able to meet future clinical needs in biomedicine.


Assuntos
Aptâmeros de Nucleotídeos/química , Ácidos Nucleicos/metabolismo , Patologia Molecular/métodos , Humanos
15.
Cell Biol Int ; 44(8): 1651-1659, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32285989

RESUMO

Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/ß-catenin pathway. We found that USP44 overexpression increased the Axin1 protein while decreasing ß-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/ß-catenin pathway. Moreover, we found that two Wnt/ß-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/ß-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the Axin1 mRNA level. Further study uncovered that USP44 interacted with Axin1 and reduced the ubiquitination of Axin1. Furthermore, Axin1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/ß-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/ß-catenin pathway via Axin1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy.


Assuntos
Proteína Axina/metabolismo , Neoplasias Colorretais/metabolismo , Ubiquitina Tiolesterase/metabolismo , Via de Sinalização Wnt , Apoptose , Proteína Axina/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Técnicas de Silenciamento de Genes , Humanos , Ubiquitina Tiolesterase/genética
16.
BMC Cardiovasc Disord ; 20(1): 454, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081697

RESUMO

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.


Assuntos
Ablação por Cateter , Terapia a Laser , Miocárdio/patologia , Animais , Ablação por Cateter/efeitos adversos , Técnicas In Vitro , Terapia a Laser/efeitos adversos , Sus scrofa , Temperatura , Fatores de Tempo
17.
J Ultrasound Med ; 38(12): 3247-3255, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31179567

RESUMO

OBJECTIVES: The purpose of this study was to assess the characterization and usefulness of contrast-enhanced ultrasound (CEUS) for diagnosing solid pseudopapillary tumors of the pancreas (SPTP) and compare the enhancement patterns with contrast-enhanced computed tomography (CECT). METHODS: Forty-three SPTP lesions proved by pathologic findings in 42 patients examined with CEUS and CECT were included in this study. The enhancement characteristics and typical CEUS features of the tumors were investigated. These characteristics were compared according to lesion sizes. The enhancement patterns of CEUS were compared with CECT. RESULTS: The most common enhancement levels of SPTP in the early phase and late phase for CEUS were isoenhancement (19 of 43 [44.2%]) and hypoenhancement (32 of 43 [74.4%]), respectively. The 4 most common enhancement patterns were hypo-hypo (16 of 43 [37.2%]), iso-iso (11 of 43 [25.6%]), hyper-hypo (8 of 43 [18.6%]), and iso-hypo (8 of 43 [18.6%]) enhancement. For the 43 SPTP lesions, typical CEUS features such as lesion membrane, intralesional vessel, and intralesional compartmentalization enhancements were detected in 30 (69.8%), 27 (62.8%), and 10 (23.2%) cases. Compared with CECT, isoenhancement during the early phase and hypoenhancement during the late phase were the most common imaging characteristics of CEUS. CONCLUSIONS: Lesion membrane, intralesional vessel, and intralesional compartmentalization enhancements are typical CEUS features of SPTP, especially for large lesions (lesion size ≥3.0 cm). Isoenhancement during the early phase and hypoenhancement during the late phase are the most common imaging characteristics of CEUS and CECT, making CEUS a viable alternative diagnostic method that is noninvasive.


Assuntos
Meios de Contraste , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto Jovem
18.
Rev Argent Microbiol ; 51(2): 170-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30297081

RESUMO

Steroids, including testosterone, estrone, 17ß-estradiol, estriol and 17ß-ethinyl estradiol, are harmful not only to the population dynamics of aquatic life forms but also to public health. In this study, a marine testosterone-degrading bacterium (strain N3) was isolated from Nanao Island in the South China Sea. In addition, the strain could also use 17ß-estradiol (E2), 17ß-ethinyl estradiol (EE2), estriol (E3) or cholesterol as a sole carbon source. According to the 16S rRNA gene sequence analysis, strain N3 was identified as Vibrio sp. Further characterization showed that the strain is aerobic, gram-negative, and mobile and exhibits resistance to ampicillin, carbenicillin, penicillin and spectinomycin. For enhancing its capacity of testosterone degradation, the Plackett-Burman factorial design and the central composite design were used to optimize the culture condition. Under optimal conditions, 92% of testosterone was degraded by Vibrio sp. N3 in 48h.


Assuntos
Testosterona/química , Vibrio/isolamento & purificação , Vibrio/fisiologia , Organismos Aquáticos , Biodegradação Ambiental , Vibrio/classificação
19.
Angew Chem Int Ed Engl ; 57(27): 8043-8047, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29741806

RESUMO

Hierarchical solution self-assembly has become an important biomimetic method to prepare highly complex and multifunctional supramolecular structures. However, despite great progress, it is still highly challenging to prepare hierarchical self-assemblies on a large scale because the self-assembly processes are generally performed at high dilution. Now, an emulsion-assisted polymerization-induced self-assembly (EAPISA) method with the advantages of in situ self-assembly, scalable preparation, and facile functionalization was used to prepare hierarchical multiscale sea urchin-like aggregates (SUAs). The obtained SUAs from amphiphilic alternating copolymers have a micrometer-sized rattan ball-like capsule (RBC) acting as the hollow core body and radiating nanotubes tens of micrometers in length as the hollow spines. They can capture model proteins effectively at an ultra-low concentration (ca. 10 nm) after functionalization with amino groups through click copolymerization.


Assuntos
Emulsões/química , Polímeros/química , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Bovinos , Química Click , Compostos de Epóxi/química , Fluoresceína-5-Isotiocianato/química , Microscopia Eletrônica de Varredura , Nanotubos/química , Polimerização , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo
20.
Langmuir ; 33(1): 340-346, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-27992208

RESUMO

This study reports the first polymer vesicle sensor for the visual detection of SO2 and its derivatives in water. A strong binding ability between tertiary alkanolamines and SO2 has been used as the driving force for the detection by the graft of tertiary amine alcohol (TAA) groups onto an amphiphilic hyperbranched multiarm polymer, which can self-assemble into vesicles with enriched TAA groups on the surface. The polymer vesicles will undergo proton exchange with cresol red (CR) to produce CR-immobilized vesicles (CR@vesicles). Subsequently, through competitive binding with the TAA groups between CR and SO2 or HSO3-, the CR@vesicles (purple) can quickly change into SO2@vesicles (colorless) with the release of protonated CR (yellow). Such a fast purple to yellow transition in the solution allows the visual detection of SO2 or its derivatives in water by the naked eye. A visual test paper for SO2 gas has also been demonstrated by the adsorption of CR@vesicles onto paper. Meanwhile, the detection limit of CR@vesicles for HSO3- is approximately 25 nM, which is improved by approximately 30 times when compared with that of small molecule-based sensors with a similar structure (0.83 µM). Such an enhanced detection sensitivity should be related to the enrichment of TAA groups as well as the CR in CR@vesicles. In addition, the CR@vesicle sensors also show selectivity and specificity for the detection of SO2 or HSO3- among anions such as F-, Br-, Cl-, SO42-, NO2-, C2O42-, S2O32-, SCN-, AcO-, SO32-, S2-, and HCO3-.

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