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1.
Cureus ; 15(9): e45154, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37842376

RESUMO

Background and objectives Previous research has suggested that hyperparathyroidism and excessive salt intake may contribute to the development of cardiac hypertrophy. This study aimed to investigate the relationship and underlying mechanisms between parathyroid hormone (PTH) and salt intake in the development of left ventricular hypertrophy (LVH). Additionally, the study sought to determine whether captopril intervention could reduce the impact of sustained PTH stimulation and excessive salt intake on LVH. Methodology We employed 40 eight-week-old male Sprague-Dawley rats, which were randomly assigned to eight groups: a sham group, a PTH group, a low-salt group (0.6% NaCl), a high-salt group (8% NaCl), a PTH + low-salt group, a PTH + high-salt group, a PTH + low salt + captopril group, and a PTH + high salt + captopril group. The rats were continuously infused with recombinant PTH (1-34) (2 pmol/kg per hour) via an osmotic pump for two weeks and were administered varying concentrations of saline for gavage over two weeks, according to their group. We monitored changes in blood pressure, measured heart weight, left ventricular wall thickness, and myocardial histological morphology, and assessed the relative expression of type III collagen. Results The PTH + high-salt group displayed a significant increase in blood pressure, heart weight, and left ventricular posterior wall thickness (P<0.05), in addition to myocardial cell hypertrophy and increased Col III expression (P<0.05), compared to other groups. Captopril intervention significantly reduced blood pressure (P<0.05), ameliorated myocardial tissue morphology changes, and significantly decreased Col III expression (P<0.05) but did not entirely reverse the increase in heart weight and left ventricular posterior wall thickness (P>0.05). Conclusions Our findings suggest that the co-intervention of PTH and high salt can lead to an increase in blood pressure, heart weight, myocardial cell hypertrophy, LVH, and myocardial fibrosis levels in Sprague-Dawley rats. Captopril intervention can lower blood pressure and alleviate pathological myocardial tissue changes and myocardial fibrosis but cannot completely reverse LVH.

2.
Exp Ther Med ; 26(3): 454, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37614422

RESUMO

Cytomegalovirus (CMV) infection is one of the most common infectious complications following hematopoietic stem cell transplantation (HSCT); however, cases involving multiple organs at the same time are rare. The present study describes a case of CMV pneumonia combined with CMV DNAemia and CMV cystitis after HSCT. A 33-year-old male patient with acute myeloid leukemia was treated with HSCT. The first month after HSCT, the patient developed a cough and shortness of breath. At 2 months post-HSCT, the patient developed hematuria. The CMV DNA levels in the blood and urine were elevated; bronchoalveolar lavage fluid (BALF) was also positive for CMV DNA. Heterotypic cells exhibiting a large nuclear morphology were observed in the BALF and bronchial brushes. Recurrent and progressive ground-glass opacities were evident on chest computed tomography. The patient was diagnosed with CMV pneumonia complicated by CMV DNAemia and CMV cystitis, and was treated with a combination of ganciclovir and foscarnet, along with immunoglobulin therapy. The patient was cured and discharged. It was determined that the CMV DNA in the blood was inconsistent with that in the BALF, which delayed the early diagnosis of CMV pneumonia. The association between T-cell immune function and the therapeutic efficacy for CMV multi-organ infection following HSCT is known to be significant. Moreover, the timely administration of ganciclovir and foscarnet in combination with immunoglobulin therapy demonstrated favorable clinical outcomes.

3.
Medicine (Baltimore) ; 102(8): e33075, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36827075

RESUMO

Bladder cancer ranked the second most frequent tumor among urological malignancies. This work investigated bladder cancer prognosis, including the relevance of pyroptosis-related long noncoding RNA (lncRNA) in it and its potential roles. The Cancer Genome Atlas database offered statistics on lncRNAs and clinical data from 411 bladder cancer patients. Pearson correlation analysis was used to evaluate pyroptosis-related lncRNAs. To explore prognosis-associated lncRNAs, we performed univariate Cox regression, least absolute shrinkage and selection operator regression analyses, as well as the Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Afterward, a nomogram was constructed according to the risk score and clinical variables. Finally, to investigate the potential functions of pyroptosis-related lncRNAs, gene set enrichment analysis was employed. Eleven pyroptosis-related lncRNAs were screened to be closely associated with patients prognosis. On this foundation, a risk score model was created to classify patients into high and low risk groups. The signature was shown to be an independent prognostic factor (P < .001) with an area under the curve of 0.730. Then a nomogram was established including risk scores and clinical characteristics. The nomogram prediction effect is excellent, with a concordance index of 0.86. The 11-lncRNAs signature was associated with the supervision of oxidative stress, epithelial-mesenchymal transition, cell adhesion, TGF-ß, and Wingless and INT-1 signaling pathway, according to the gene set enrichment analysis. Our findings indicate that pyroptosis-related lncRNAs, which may affect tumor pathogenesis in many ways, might be exploited to assess the prognosis of bladder cancer patients.


Assuntos
Segunda Neoplasia Primária , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , Piroptose , Prognóstico , Nomogramas , Biomarcadores Tumorais
4.
Front Oncol ; 12: 951631, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992824

RESUMO

Background: Bladder cancer is ranked the second most frequent tumor among urological malignancies. The research strived to establish a prognostic model based on endoplasmic reticulum stress (ERS)-related long non-coding RNA (lncRNA) in bladder cancer. Methods: We extracted the ERS-related genes from the published research and bladder cancer data from the Cancer Genome Atlas database. ERS-related lncRNAs with prognostic significance were screened by univariate Cox regression, least absolute shrinkage and selection operator regression analysis and Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Moreover, an independent dataset, GSE31684, was used to validate the model's efficacy. The nomogram was constructed based on the risk score and clinical variables. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the ERS-related signature. Finally, we employed external datasets (GSE55433 and GSE89006) and qRT-PCR to investigate the expression profile of these lncRNAs in bladder cancer tissues and cells. Results: Six ERS-related lncRNAs were identified to be closely coupled with patients' prognosis. On this foundation, a risk score model was created to generate the risk score for each patient. The ERS-related risk score was shown to be an independent prognostic factor. And the results of GSE31684 dataset also supported this conclusion. Then, a nomogram was constructed based on risk scores and clinical characteristics, and proven to have excellent predictive value. Moreover, the gene function analysis demonstrated that ERS-related lncRNAs were closely linked to fatty extracellular matrix, cytokines, cell adhesion, and tumor pathways. Further analysis revealed the association of the 6-lncRNAs signature with gene mutations and immunity in bladder cancer. Finally, the external datasets and qRT-PCR verified high expressions of the ERS-related lncRNAs in bladder cancer tissues and cells. Conclusions: Overall, our findings indicated that ERS-related lncRNAs, which may affect tumor pathogenesis in a number of ways, might be exploited to assess the prognosis of bladder cancer patients.

5.
J Hazard Mater ; 428: 128213, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35007970

RESUMO

Pretreatment is widely used in sludge dewatering, however, its potentially impact on the subsequent sludge agricultural applications is often neglected. Here, the potential benefits and risks of the sludge with no pretreatment and with four most commonly used pretreatment methods in sludge agricultural applications were assessed using potted lettuce, an experimental crop. The results show that sewage sludge pretreatment methods can greatly affect its agricultural applications. The application of different pretreatment methods can potentially reduce the harm caused by pathogens. At low dosage (0.2 g kg-1), different sludge fertilizers promoted an increase in crop yield of 14.6% to 49.1%, and the concentrations of heavy metals in the crop and soil were controlled within safe ranges. At high dosage (8 g kg-1), crop yield using pretreated sludge (except anaerobic digestion) decreased by between 32.7% and 57.5%, but heavy metal pollution of both crop and soil increased. In terms of promoting crop growth and reducing heavy metal accumulation, untreated sludge was better than pretreated sludges and sludge with physical pretreatments was better than that with chemical pretreatments. Overall, this study clearly shows that the introduction of pretreatment in sludge dewatering can inevitably impact its agricultural land application.


Assuntos
Metais Pesados , Poluentes do Solo , Fertilizantes/análise , Metais Pesados/análise , Esgotos , Solo , Poluentes do Solo/análise
6.
Appl Radiat Isot ; 179: 110028, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34800759

RESUMO

The traditional nuclear pulse signal generator outputs the nuclear pulse signal of specific waveform according to the input pulse amplitude probability distribution and counting rate, following the signal output laws of radiation detector in both pulse amplitude and time interval. However, the output waveform is generally regulated by an analog circuit, with the single waveform and difficult parameter adjustment. In this study, the digital C-R and R-C filters were explored, a cascading digital C-R or R-C filter algorithm was proposed, realizing multiple pragmatic nuclear pulse signal outputs through the serial or parallel connection of multiple digital filters. The actual test results show that the nuclear pulse signal generator constructed by this algorithm can simulate the nuclear pulse signals under different detectors and counting rates, thus expanding the scope of application and improving the flexibility of digital nuclear pulse signal generators.

7.
Zhongguo Gu Shang ; 34(12): 1141-6, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34965632

RESUMO

OBJECTIVE: To compare the clinical outcomes and complications of hip arthroscopic treatment for femoroacetabular impingement (FAI) performed with either Inside-out or Outside-in approach. METHODS: The clinical date of 48 patients with FAI treated by hip arthroscopy surgery and follow-up from June 2016 to June 2019 were retrospectively analyzed. According to the different operative methods, the patients were divided into two groups. Inside-out group, from central compartment to peripheral compartment;Outside-in group, from peripheral compartment to central compartment. There were 14 males and 10 females in Inside-out group with an averageage of (39.8±7.6)years old, 13 males and 11 females in Inside-out group with an average age of (39.5±9.1)years old in Outside-in group. There was no significant difference in age, gender, body mass index, side, impingement type, medical history and follow-up time between the two groups. The complication occurrence rate, modified Harris hip score (mHHS)and nonarthritic hip score (NAHS) were compared between these two groups. RESULTS: The mHHs and NAHS scores of the two groups were significantly higher than those before operation, but there was no significant difference between the two groups (P>0.05). In the Inside-out group, there were 4 cases of nerve traction injury and 3 cases of iatrogenic injury, while only 1 case of nerve traction injury occurred in the Outside-in group. The incidence of complications in the inside out group was higher than that in the outside in group (16.7% vs 4.2%, χ2=5.400, P=0.020). CONCLUSION: Both hip arthroscopic surgery methods can obtain satisfactory clinical efficacy in the treatment of FAI, but the incidence of postoperative complications of Outside-in surgical method is lower. The out-side in method can be preferentially selected for the patients with the indications of operation.


Assuntos
Impacto Femoroacetabular , Adulto , Artroscopia , Feminino , Impacto Femoroacetabular/cirurgia , Seguimentos , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Int J Clin Pract ; 75(10): e14537, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132007

RESUMO

OBJECTIVE: To examine the association between hip and knee osteoarthritis (OA) and falls. Potentially relevant articles that examine the association between hip, knee, radiological, and self-reported OA and falls were retrieved from PubMed, EMBASE, Scopus, and Web of Science up until March of 2020. METHODS: The pooled risk ratios (RRs) as well as their related 95% confidence intervals (CIs) were calculated. Statistic and subgroup analyses were performed. A total of 21 studies involving 146 965 participants were included. RESULTS: No association was found between hip OA and falls. The pooled RRs value suggested a higher prevalence of falls in knee OA patients (RR = 1.35, 95% CI: 1.20 to 1.51, P < .00001) and self-reported OA (RR = 1.33, 95% CI: 1.23 to 1.45, P < .00001) than in non-OA subjects. The pooled RR value suggested no difference between prevalence of falls in radiological OA patients compared to non-OA subjects (RR = 1.82, 95% CI: 0.89 to 3.73, P = .10). Both radiological and self-reported knee OA seem to be positively associated with falls, while no obvious association was found between hip OA and falls. CONCLUSIONS: Therefore, knee OA is a risk factor for falls which should be closely monitored.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Prevalência , Fatores de Risco
9.
Int Immunopharmacol ; 96: 107775, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162143

RESUMO

Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 µg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 µmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 µmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 µg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.


Assuntos
Eritromicina/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Produtos do Tabaco , Proliferação de Células/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Macrófagos/metabolismo , PPAR gama/genética , Espécies Reativas de Oxigênio/metabolismo , Fumaça/efeitos adversos , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Células U937
10.
J Biomater Appl ; 35(10): 1264-1274, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33632006

RESUMO

Magnesium alloys have been widely investigated as biodegradable cardiovascular temporal implants due to their better mechanical properties and biocompatibility, but the rapid degradation limited its application. In this study, the anodic oxidation-Cu structure was used to improve the adhesive strength and stability between poly-ß-hydroxybutyrate (PHB) and magnesium alloys, and the effects of anodic oxidation magnesium alloys with copper film and PHB film (MACP) on human umbilical vein endothelial cells (HUVECs), blood compatibility and antibacterial properties were investigated in this research. As the result, the MACP structure had a stable structure and better corrosion resistance, and significant antibacterial properties. The coating would not affect the original excellent biocompatibility of the magnesium alloy. It was indicated that MACP was a potential surface modification strategy for vascular stents candidate material.


Assuntos
Ligas/química , Materiais Revestidos Biocompatíveis/química , Hidroxibutiratos/química , Poliésteres/química , Plaquetas/citologia , Plaquetas/metabolismo , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Cobre/química , Corrosão , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/patologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Hemólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Magnésio/química
11.
Sci Rep ; 11(1): 2374, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504927

RESUMO

Klotho, an important anti-aging protein, may be related to elevated blood pressure (BP) and arterial stiffness. We aimed to investigate associations between the serum klotho concentration and peripheral/central BP and arterial stiffness based on the carotid-femoral pulse wave velocity (cfPWV) in a Chinese population. We invited all inhabitants aged ≥ 18 years in two Dali communities for participation. The SphygmoCor system was used to record radial arterial waveforms. Aortic waveforms were derived using a generalized transfer function. The central BP was assessed by calibrating the brachial BP, which was measured using an oscillometric device. The serum klotho concentration was measured using an enzyme-linked immunosorbent assay and logarithmically transformed. Of the 716 participants (mean age: 51.9 ± 12.6 years), 467 (65.2%) were women. The median serum klotho concentration was 381.8 pg/mL. The serum klotho concentration did not significantly differ between patients with and without hypertension (P > 0.05) and between those with and without arterial stiffness (cfPWV ≥ 10 m/s) (P > 0.05). After adjusting for confounders, the serum klotho concentration was not significantly associated with the peripheral or central BP (P > 0.05) and cfPWV (P > 0.05). Our data indicated that the serum klotho concentration was not associated with BP or cfPWV in the general Chinese population.


Assuntos
Biomarcadores , Pressão Sanguínea , Glucuronidase/sangue , Adulto , China/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Análise de Onda de Pulso
12.
J Clin Hypertens (Greenwich) ; 23(2): 363-372, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33369115

RESUMO

Thyroid dysfunction plays a role in blood pressure (BP) regulation. However, the associations between thyroid function and BP and arterial stiffness in the general Chinese population without thyroid disease are unknown. This population-based cross-sectional study aimed to investigate the association between thyroid function and peripheral and central BP and arterial stiffness in Chinese individuals. After excluding those who had thyroid diseases or incomplete clinical measurements, this study included 691 participants. Of the participants, 444 (64.2%) were women and 215 (31.1%) had hypertension. After adjustment for covariates, serum FT3 was significantly associated with a higher pulse rate in both sexes. In men, each 2.72-fold increase in serum FT4 levels was associated with higher peripheral systolic BP (+10.82 mmHg, p = .005) and pulse pressure (+5.71 mmHg, p = .03). Each 2.72-fold increase in serum FT4 levels was associated with higher central systolic BP (+8.03 mmHg, p = .03) and pulse pressure (+3.89 mmHg, p = .05). In women, serum FT4 was only associated with a higher central pulse pressure (+2.96 mmHg, p = .04). After adjustment for covariates, serum FT4 was significantly associated with a faster cfPWV exclusively in men. Our study showed that serum FT4 is associated with higher peripheral and central BP and faster cfPWV in men, whereas serum FT3 is positively associated with a higher pulse rate in both sexes, indicating that the effects of thyroid function on BP and arterial stiffness are more significant in men than in women.


Assuntos
Hipertensão , Rigidez Vascular , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Hormônios Tireóideos
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-921939

RESUMO

OBJECTIVE@#To compare the clinical outcomes and complications of hip arthroscopic treatment for femoroacetabular impingement (FAI) performed with either Inside-out or Outside-in approach.@*METHODS@#The clinical date of 48 patients with FAI treated by hip arthroscopy surgery and follow-up from June 2016 to June 2019 were retrospectively analyzed. According to the different operative methods, the patients were divided into two groups. Inside-out group, from central compartment to peripheral compartment;Outside-in group, from peripheral compartment to central compartment. There were 14 males and 10 females in Inside-out group with an averageage of (39.8±7.6)years old, 13 males and 11 females in Inside-out group with an average age of (39.5±9.1)years old in Outside-in group. There was no significant difference in age, gender, body mass index, side, impingement type, medical history and follow-up time between the two groups. The complication occurrence rate, modified Harris hip score (mHHS)and nonarthritic hip score (NAHS) were compared between these two groups.@*RESULTS@#The mHHs and NAHS scores of the two groups were significantly higher than those before operation, but there was no significant difference between the two groups (@*CONCLUSION@#Both hip arthroscopic surgery methods can obtain satisfactory clinical efficacy in the treatment of FAI, but the incidence of postoperative complications of Outside-in surgical method is lower. The out-side in method can be preferentially selected for the patients with the indications of operation.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artroscopia , Impacto Femoroacetabular/cirurgia , Seguimentos , Articulação do Quadril/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Med Chem ; 63(14): 7857-7866, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32588620

RESUMO

In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (3e, 3g, and 3j) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia. Their molar dose, onset time, and anesthesia duration time were comparable to those of propofol, helping to maintain the clinical benefits of propofol. The experimental results showed the potential of such compounds as water-soluble prodrugs of propofol.


Assuntos
Aminoácidos Cíclicos/farmacologia , Anestésicos Intravenosos/farmacologia , Glicolatos/farmacologia , Pró-Fármacos/farmacologia , Propofol/farmacologia , Aminoácidos Cíclicos/síntese química , Anestésicos Intravenosos/síntese química , Animais , Desenho de Fármacos , Glicolatos/síntese química , Masculino , Camundongos , Pró-Fármacos/síntese química , Propofol/síntese química , Solubilidade , Água/química
15.
J Enzyme Inhib Med Chem ; 35(1): 773-785, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32200656

RESUMO

Basis on molecular docking and pharmacophore analysis of naphthoquinone moiety, a total of 23 compounds were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC50 against SGC-7901 was 4.1 ± 2.6 µM. Meanwhile the anticancer mechanism of compound 12 had been investigated by AnnexinV/PI staining, immunofluorescence, Western blot assay and molecular docking. The results indicated that this compound might induce cell apoptosis and cell autophagy through regulating the PI3K signal pathway.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Naftoquinonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
16.
Bioorg Chem ; 96: 103624, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32078847

RESUMO

A major goal of medicinal chemists is to identify and validate novel and effective kinase targets for treatment of cancer. Recent studies have shown that cyclin-dependent kinase 8 (CDK8) is a target for treatment of colorectal, breast, melanoma, and prostate cancers. The crystal structure of CDK8 has been reported, and eutectic interactions have been identified for 24 compounds that target CDK8. To more effectively develop CDK8 inhibitors, particularly those with improved selectivity, we summarized the structure, structure-activity relationships, and binding information of typical CDK8 inhibitors, which may serve as a reference for development of novel CDK8 inhibitors.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Quinase 8 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Animais , Quinase 8 Dependente de Ciclina/química , Quinase 8 Dependente de Ciclina/metabolismo , Descoberta de Drogas , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/metabolismo , Relação Estrutura-Atividade
17.
J Cell Physiol ; 235(3): 2492-2505, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31565805

RESUMO

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células/genética , MicroRNAs/genética , Proteínas Repressoras/genética , Câncer Papilífero da Tireoide/genética , Adulto , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Notch/genética , Transdução de Sinais/genética , Taxa de Sobrevida , Câncer Papilífero da Tireoide/patologia
18.
J Cell Physiol ; 235(3): 2403-2413, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31556116

RESUMO

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.


Assuntos
Proliferação de Células/genética , RNA Longo não Codificante/genética , Transportadores de Sulfato/genética , Câncer Papilífero da Tireoide/genética , Animais , Apoptose/genética , Caderinas/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Câncer Papilífero da Tireoide/patologia
19.
Cancer Manag Res ; 11: 10657-10663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920375

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) plays different roles in different types of human cancer, but its role in prostate cancer (PC) has not been reported. METHODS: DGCR5 and TGF-ß1 expression in paired tumor and adjacent healthy tissues from 64 PC patients was analyzed by performing RT-qPCR. A 5-year follow-up study was performed to analyze the prognostic value of DGCR5 for PC. The interaction between DGCR5 and TGF-ß1 was analyzed by overexpression experiments. Cell stemness was analyzed by cell stemness assay. RESULTS: In our study, we found that DGCR5 was down-regulated in tumor tissues than in adjacent healthy tissues of PC patients, but TGF-ß1 was up-regulated in the tumor tissues. DGCR5 expression was not affected by clinical stages, but low DGCR5 level in the tumor was correlated with poor survival. DGCR5 and TGF-ß1 were inversely correlated in tumor tissues but not in adjacent healthy tissues. DGCR5 over-expression resulted in down-regulation of TGF-ß1, while TGF-ß1 treatment did not significantly affect DGCR5 expression. DGCR5 over-expression led to decreased stemness of PC cells, but TGF-ß1 treatment played a reverse role and attenuated the effects of DGCR5 over-expression. DGCR5 may decrease the stemness of PC cells by down-regulating TGF-ß1.

20.
Open Med (Wars) ; 14: 913-919, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934637

RESUMO

OBJECTIVE: To investigate the involvement of miR-520e in the modulation of cancer-promoting cyclinD1 in breast cancer. METHODS: A reverse transcription-polymerase chain reaction (RT-PCR) was applied to test the regulation of miR-520e on cyclinD1. The binding of miR-520e to 3'-untranslated region (3'UTR) of cyclinD1 mRNA was predicted by an online bioinformatics website. The effect of miR-520e on the luciferase reporters with binding sites of miR-520e and 3'UTR of cyclinD1 mRNA was revealed using a luciferase reporter gene assay. The correlation between miR-520e and cyclinD1 in clinical breast cancer samples was detected through quantitative real-time PCR. RESULTS: The expression of cyclinD1 was gradually reduced as the dose of miR-520e increased. Anti-miR-520e obviously induced cyclinD1 in breast cancer cells. After anti-miR-520e was introduced into the cells, the inhibition of cyclinD1 expression mediated by miR-520e was reversed. The binding of miR-520e with cyclinD1 was revealed via bioinformatics. Under the treatment of dose-increasing miR-520e or anti-miR-520e, the luciferase activities of cyclinD1 3'UTR vector were lower or higher by degrees. However, the activity of the mutant vector was not affected at all. Finally, in clinical breast cancer tissues the negative correlation of miR-520e with cyclinD1 was revealed. CONCLUSION: In conclusion, cyclinD1 is a new target of miR-520e in breast cancer.

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