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1.
Materials (Basel) ; 17(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38730894

RESUMO

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

2.
Int Immunopharmacol ; 132: 111980, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38555819

RESUMO

BACKGROUND: In our previous study, Cu(sal)phen was found to have anti-tumor effects, yet its precise mechanism remains unknown. Research has shown that dying tumor cells release damage-associated molecular patterns (DAMPs) to promote anti-tumor immune response. Therefore, we have further explored the effects and potential molecular mechanisms of Cu(sal)phen-induced immunogenic cell death (ICD) in colorectal cancer (CRC). METHODS: ELISA and flow cytometry were used to detect the effects of Cu(sal)phen treatment on ICD markers. The molecular mechanisms of Cu(sal)phen-induced ICD were investigated through the detection of endoplasmic reticulum stress (ERS) and reactive oxygen species (ROS) in vitro using Western blot and flow cytometry. Additionally, a mouse model was constructed to study the effects of Cu(sal)phen on immune cells and anti-tumor-related cytokines in vivo. RESULTS: Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD, by promoting the accumulation of ROS and inducing ERS. Furthermore, Cu(sal)phen promoted the maturation of dendritic cells (DCs) and activation of CD8+T cells, as well as the secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ), while downregulating transforming growth factor-ß (TGF-ß) levels, thereby activating the anti-tumor immune response. CONCLUSION: Cu(sal)phen has the potential to induce ICD in tumors and activate the adaptive immune response to achieve anti-tumor effects. This makes Cu(sal)phen a promising candidate for the treatment of CRC.


Assuntos
Neoplasias Colorretais , Cobre , Estresse do Retículo Endoplasmático , Morte Celular Imunogênica , Fenantrolinas , Espécies Reativas de Oxigênio , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Animais , Morte Celular Imunogênica/efeitos dos fármacos , Humanos , Camundongos , Fenantrolinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Salicilatos/farmacologia , Linhagem Celular Tumoral , Proteína HMGB1/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Calreticulina/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Complexos de Coordenação/farmacologia
3.
Oncol Rep ; 50(3)2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37503758

RESUMO

Oxaliplatin (Oxa) is one of the most effective chemotherapeutic drugs used in the treatment of colorectal cancer (CRC). However, the use of this drug is associated with severe side­effects and patients eventually develop resistance to Oxa. In recent years, copper complexes have been extensively investigated as substitutes for platinum­based drugs. Therefore, a number of copper complexes have also been developed for cancer therapy, such as copper (II) complex of salicylate phenanthroline [Cu(sal)(phen)]. In the present study, the antitumor activity and the related molecular mechanisms of Cu(sal)(phen) were examined in CRC cells. As compared with the chemotherapeutic drug, Oxa, Cu(sal)(phen) was more effective in inducing apoptosis and reactive oxygen species (ROS) production, and in decreasing mitochondrial membrane potential in the CRC cell lines, HCT116 and SW480. In addition, the expression of the apoptosis­related proteins, Bcl­2 and survivin, and those of the upstream regulators, p­JAK2 and p­STAT5, were significantly decreased in the two cell lines following treatment with Cu(sal)(phen). Furthermore, the efficacy of the complex against CRC was found to be excellent in an animal model. The results of immunohistochemical analysis revealed that the expression levels of Bcl­2, survivin and Ki­67 in tumor tissues were decreased following Cu(sal)(phen) treatment. The antitumor mechanisms underlying Cu(Sal)(phen) treatment were the induction of ROS generation, the inhibition of the JAK2/STAT5 signaling pathway and the downregulation of the expression of anti­apoptotic proteins, such as Bcl­2 and survivin. On the whole, the findings of the present study indicated that Cu(sal)(phen) effectively inhibited the viability and proliferation of HCT116 and SW480 CRC cells; in the future, the authors aim to conduct further experiments in future studies to provide more evidence that supports the development of Cu(sal)(phen) as a therapeutic agent for CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Animais , Oxaliplatina/farmacologia , Cobre/farmacologia , Cobre/química , Cobre/metabolismo , Survivina/metabolismo , Fenantrolinas/farmacologia , Fenantrolinas/química , Fator de Transcrição STAT5/metabolismo , Fator de Transcrição STAT5/farmacologia , Salicilatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Linhagem Celular Tumoral
4.
Sci Total Environ ; 892: 164748, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37308018

RESUMO

Bisphenol P (BPP) and bisphenol M (BPM) are increasing in our living environment as analogues of bisphenol A (BPA), but little is known about their biological effect. In this study, we investigated the effects of low to medium dose exposure of BPP and BPM on triple negative breast cancer (TNBC). We found that BPP and BPM exposure didn't affect proliferation of TNBC cell lines MDA-MB-231 and 4 T1, but significantly promoted cells migration and invasion. The effect of BPP and BPM on promoting TNBC metastasis was further confirmed in mouse models. Low concentrations of BPP and BPM significantly increased the expression of epithelial-mesenchymal transition (EMT) marker and related proteins such as N-cadherin, MMP-9, MMP-2 and Snail, and also enhanced phosphorylation of AKT both in vitro and in vivo. When PI3K inhibitor wortmannin was applied to specifically inhibit phosphorylation of AKT, the expression of target genes markedly decreased, and the TNBC metastasis induced by low-concentration BPP and BPM were reversed. In conclusion, these results showed that PI3K/AKT signaling regulate BPP/BPM-induced metastasis of TNBC by triggering EMT. This study provides insights into the effects and the potential mechanisms of BPP and BPM on TNBC, raising concerns about the risk of using these two bisphenols as the alternative of BPA.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células
5.
J Alzheimers Dis ; 94(1): 393-404, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37248898

RESUMO

BACKGROUND: The Boston Naming Test (BNT) is the most widely used measure to assess anomia. However, it has been criticized for failing to differentiate the underlying cognitive process of anomia. OBJECTIVE: We validated the color-picture version of BNT (CP-BNT) in a sample with diverse neurodegenerative dementia diseases (NDDs). We also verified the differential ability of the composite indices of CP-BNT across NDDs groups. METHODS: The present study included Alzheimer's disease (n = 132), semantic variant primary progressive aphasia (svPPA, n = 53), non-svPPA (n = 33), posterior cortical atrophy (PCA, n = 35), and normal controls (n = 110). We evaluated psychometric properties of CP-BNT for the spontaneous naming (SN), the percentage of correct responses on semantic cuing and word recognition cuing (% SC, % WR). Receiver operating characteristic analysis was used to examine the discriminatory power of SN alone and the composite indices (SN, % SC, and % WR). RESULTS: The CP-BNT had sufficient internal consistency, good convergent, divergent validity, and criterion validity. Different indices of CP-BNT demonstrated distinct cognitive underpinnings. Category fluency was the strongest predictor of SN (ß= 0.46, p < 0.001). Auditory comprehension tests highly associated with % WR (Sentence comprehension: ß= 0.22, p = 0.001; Word comprehension: ß= 0.20, p = 0.001), whereas a lower visuospatial score predicted % SC (ß= -0.2, p = 0.001). Composite indices had better predictability than the SN alone when differentiating between NDDs, especially for PCA versus non-svPPA (area under the curve increased from 63.9% to 81.2%). CONCLUSION: The CP-BNT is a highly linguistically relevant test with sufficient reliability and validity. Composite indices could provide more differential information beyond SN and should be used in clinical practice.


Assuntos
Anomia , Testes de Linguagem , Doenças Neurodegenerativas , Humanos , Anomia/diagnóstico , Anomia/etiologia , População do Leste Asiático , Doenças Neurodegenerativas/complicações , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Afasia Primária Progressiva/complicações , Doença de Alzheimer/complicações , Demência/complicações
6.
Environ Toxicol ; 38(6): 1384-1394, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36891644

RESUMO

In the present study, we investigated the antitumor effect and associated molecular mechanisms of the copper (II) complex of salicylate phenanthroline [Cu(sal)(phen)] against hepatocellular carcinoma (HCC). Cu(sal)(phen) inhibited the proliferation of HCC cells (HepG2 and HCC-LM9) and induced apoptosis of HCC cells in a dose-dependent manner by upregulating mitochondrial reactive oxygen species (ROS) production. The expression of the antiapoptotic proteins survivin and Bcl-2 was decreased, while the expression of the DNA damage marker γ-H2 AX and the apoptotic marker cleaved PARP was upregulated with Cu(sal)(phen) treatment. In vivo, the growth of HepG2 subcutaneous xenograft tumors was greatly attenuated by Cu(sal)(phen) treatment. Immunohistochemistry staining showed that the expression of survivin, Bcl-2, and Ki67 in the tumor was downregulated by Cu(sal)(phen). Toxicity experiments with BALB/c mice revealed that Cu(sal)(phen) is a relatively safe drug. Our results indicate that Cu(sal)(phen) possesses great potential as a therapeutic drug for HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/patologia , Survivina/farmacologia , Survivina/uso terapêutico , Cobre/toxicidade , Cobre/química , Fenantrolinas/farmacologia , Fenantrolinas/química , Fenantrolinas/uso terapêutico , Neoplasias Hepáticas/patologia , Salicilatos/farmacologia , Salicilatos/química , Salicilatos/uso terapêutico , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Proliferação de Células , Linhagem Celular Tumoral , Antineoplásicos/uso terapêutico , Células Hep G2
7.
Angiology ; 74(6): 545-552, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35815550

RESUMO

The studies investigated the predictive value of the contrast media volume to creatinine clearance ratio (V/CrCl) for contrast-induced nephropathy (CIN) after a percutaneous coronary intervention (PCI) showed conflicting results and different cut-off values. The objective is to evaluate V/CrCl in the prediction of CIN after PCI. PubMed, Embase, and the Cochrane library were searched for eligible studies published from inception to November 2020. The optimal cut-off points of V/CrCl for predicting CIN were examined using odds ratios (ORs) and 95% confidence intervals (CIs). The random-effect model was used for analyses. Six studies (8 datasets, 16 899 patients) were included. V/CrCl was associated with CIN (OR = 2.67, 95% CI: 1.88-3.78, P < .001; I2 = 79.3%, Pheterogeneity < .001). V/CrCl was associated with CIN in Asians (OR = 2.13, 95% CI: 1.52-2.98, P = .022; I2 = 68.8%, Pheterogeneity < .001) and Europeans (OR = 3.87, 95% CI: 1.77-8.45, P < .001; I2 = 85.1%, Pheterogeneity = .001). The association between V/CrCl and CIN was observed in the prospective cohort studies (OR = 2.16, 95% CI: 1.42-3.29, P = .009; I2 = 78.9%, Pheterogeneity < .001) and retrospective cohort studies (OR = 3.31, 95% CI: 1.82-6.02, P < .001; I2 = 80.6%, Pheterogeneity < .001). The sensitivity analysis showed the results were robust. V/CrCl is independently associated with an increased risk of CIN. V/CrCl could be considered a reliable predictor for the development of CIN in patients undergoing PCI.


Assuntos
Nefropatias , Intervenção Coronária Percutânea , Humanos , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Creatinina , Estudos Prospectivos , Estudos Retrospectivos , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Angiografia Coronária/efeitos adversos , Fatores de Risco
8.
Front Neurol ; 13: 884460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547369

RESUMO

Despite the ubiquity of the Boston naming test (BNT) in clinical practice and research, concerns have been expressed about its poor quality pictures, insufficient psychometric properties, and cultural bias in non-English language backgrounds. We modified the black-and-white BNT with a set of color pictures since color effects have been suggested to improve naming accuracy in the visual naming test. This study aimed to examine and compare the reliability and validity of the color-picture version of BNT (CP-BNT) and the black-and-white version of BNT (BW-BNT) to differentiate amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD) from the cognitive normals. This study included two subgroups, and each subgroup had 101 normal controls, 51 aMCI, and 52 mild AD. One subgroup undertook BW-BNT and the other conducted CP-BNT. The reliability, convergent and discriminant validity, and the diagnostic accuracy of two versions of BNT were evaluated. The CP-BNT showed a greater area under the curve (AUC) than the BW-BNT for aMCI (80.3 vs.s 69.4%) and mild AD (93.5 vs. 77.6%). The CP-BNT also demonstrated better convergent validity with CDR global scores and better reliability (Cronbach's coefficient 0.66 for the CP-BNT vs. 0.55 for the BW-BNT). At the optimal cutoff value of spontaneous naming, the CP-BNT demonstrated improved sensitivity and specificity for differentiating mild AD from NC with a higher positive predictive value, negative predictive value, and lower false-positive rate. Compared with BW-BNT, CP-BNT is a more reliable and valid test to assess cognitive and naming impairment.

9.
Sci Rep ; 12(1): 4545, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296801

RESUMO

The zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH3)3C]2Sal}22-) is a zinc ion chelate of salicylate. In this study, we found that this compound inhibits viability, invasion, and migration and induces apoptosis in triple-negative breast cancer 4T1 cells. RNA-seq showed that the expression of 17 genes was upregulated and 26 genes were downregulated significantly by Zn{[CH3)3C]2Sal}22- treatment. Further GO and KEGG analysis showed that the activity of Zn{[CH3)3C]2Sal}22- against triple-negative breast cancer cells may be involved in the JAK-STAT3, HIF-1, and TNF signaling pathways. The expression of key genes was verified by RT-PCR. The phosphorylation of STAT3 and its upstream SRC decreased drastically upon Zn{[CH3)3C]2Sal}22- treatment, as demonstrated by western blot. Our results indicate that Zn{[CH3)3C]2Sal}22- inhibits the activity of TNBC cells by downregulating the STAT3 signaling through the SRC pathway.


Assuntos
Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Humanos , Salicilatos/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Zinco/farmacologia
11.
Oncol Rep ; 45(2): 513-522, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416159

RESUMO

Ovarian cancer is a gynecological malignancy with high mortality. Adjuvant therapy such as chemoradiotherapy inevitably leads to side effects and drug resistance. In recent years, traditional Chinese medicine has been widely studied for its safety, effectiveness, and unique pharmacological effects. Polyphyllin VII is an important component of Rhizoma paridis saponins, and has cytotoxic effects on many types of cancer cells. The aim of the present study was to evaluate the anti­tumor activity of polyphyllin VII in human ovarian cancer cells. Recent studies found that polyphyllin VII induces mitochondrial pathway apoptosis by increasing mitochondrial division, but the specific mechanism was unclear. The results of this study revealed that polyphyllin VII could effectively induce mitochondrial dysfunction, including increased mitochondrial division and reactive oxygen species (ROS) production. Notably, the mitochondrial location of dynamin­related protein 1 (DRP1) plays an important role in its function. In addition, polyphyllin VII enhanced the mitochondrial localization of DRP1 which is mediated by increased protein phosphatase 2A (PP2A) activity, and decreased AKT activity. A specific PP2A inhibitor, LB100, attenuated mitochondrial division and apoptosis in cells caused by polyphyllin VII, confirming the function of the PP2A/AKT pathway in polyphyllin VII treatment. Additionally, xenotransplantation experiments have also confirmed the anti­tumor effect of polyphyllin VII in vivo. Therefore, interference of the mitochondrial translocation of DRP1 through PP2A/AKT pathway may be an attractive and effective therapeutic approach by polyphyllin VII in ovarian cancer. This may provide new strategies for polyphyllin VII in the clinical treatment of ovarian cancer.


Assuntos
Mitocôndrias/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Fracionamento Celular , Linhagem Celular Tumoral , Dinaminas/metabolismo , Feminino , Humanos , Camundongos , Mitocôndrias/patologia , Neoplasias Ovarianas/patologia , Piperazinas/farmacologia , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Medicine (Baltimore) ; 99(35): e21881, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871917

RESUMO

BACKGROUND: Pain control after total knee arthroplasty has shown many advances; however, the optimal method remains controversial. The purpose of this present study is to assess the efficacy and safety of the addition of local infiltration analgesia to adductor canal block for pain control after primary total knee arthroplasty. METHODS: This prospective randomized controlled research was conducted from January 2018 to June 2019. All the patients and their family members signed the informed consent forms, and this work was authorized via the ethics committee of Jinxiang Hospital Affiliated to Jining Medical College (JXHP0024578). Inclusion criteria were 55 years old or older, who possess the physical status I-III of American Society of Anesthesiologists, and the body mass index in the range of 18 to 30 kg/m. Exclusion criteria were regional and/or neuroaxial anesthesia contraindications, the history of drug allergy involved in the research, neuropathic pain, as well as the chronic pain requiring opioid therapy. Seventy-two patients were divided into 2 groups randomly. Study group (n = 36) received both adductor canal block and local infiltration analgesia. Control group (n = 36) received adductor canal block alone. Primary outcome included postoperative pain score (visual analog scale 0 to 10 cm, in which 0 represents no pain and 10 represents the most severe imaginable pain). The measures of secondary outcome included the knee range of motion, opioid consumption, the hospital stay length as well as the postoperative complications (for instance, pulmonary embolism, deep vein thrombosis, and the wound infection). All the analyses were conducted through utilizing the SPSS for Windows Version 20.0. RESULTS: The results will be shown in .(Table is included in full-text article.) CONCLUSION:: The study will provide more evidence on the combination use of adductor canal block and local infiltration analgesia in the treatment of pain after the total knee arthroplasty. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5832).


Assuntos
Anestésicos Locais/administração & dosagem , Artroplastia do Joelho , Bloqueio Nervoso , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Bupivacaína/administração & dosagem , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Ropivacaina/administração & dosagem , Escala Visual Analógica
13.
Onco Targets Ther ; 13: 685-699, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158221

RESUMO

PURPOSE: A long noncoding RNA called small nucleolar RNA host gene 7 (SNHG7) is known to be a key regulator of biological processes in multiple human cancer types. In this study, our aims were to determine the expression status of SNHG7 in cervical cancer, to figure out the detailed roles of SNHG7 in cervical cancer cells, and to identify the mechanism underlying the activity of SNHG7 in cervical cancer. METHODS: Reverse-transcription quantitative PCR was performed to measure SNHG7 expression in cervical cancer. A Cell Counting Kit-8 assay, flow-cytometric analysis, cell migration and invasion assays, and a tumor xenograft experiment were conducted to respectively determine the effects of SNHG7 on cervical cancer cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. RESULTS: SNHG7 was found to be markedly upregulated in cervical cancer tissues and cell lines. Higher SNHG7 expression significantly correlated with FIGO stage, lymph node metastasis, the depth of cervical invasion, and shorter overall survival in patients with cervical cancer. Functional experiments indicated that a SNHG7 knockdown attenuated proliferation, migration, and invasiveness and promoted apoptosis of cervical cancer cells in vitro. The SNHG7 knockdown also slowed tumor growth in vivo. Further investigation showed that SNHG7 acts as a competing endogenous RNA for microRNA-485 (miR-485) in cervical cancer cells, and the inhibitory actions of the SNHG7 knockdown on the malignant phenotype were reversed by miR-485 inhibition. P21-activated kinase 4 (PAK4) was identified as a direct target gene of miR-485 in cervical cancer, and PAK4 expression was promoted by SNHG7. CONCLUSION: SNHG7 functions as an oncogenic RNA in cervical cancer, competitively binds to miR-485, and thereby upregulates PAK4. This SNHG7-miR-485-PAK4 regulatory network may provide insights into the pathogenesis of cervical cancer, and can help in the identification of novel diagnostic and therapeutic approaches for cervical cancer.

14.
Cell Cycle ; 18(19): 2454-2464, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31411527

RESUMO

In a variety of cancers, long non-coding RNAs (lncRNAs) were believed to play important roles. Nevertheless, H19's possible molecular mechanism related to miR-20b-5p has not yet been explored in endometrial cancer. Differential lncRNAs in endometrial cancer were identified based on microarray analysis (GSE23339). In this research, in the first place, H19 expression was detected to be increased but miR-20b-5p to be decreased in endometrial cancer tissues and cells. Besides, H19 expression displayed a negative relationship to miR-20b-5p expression in endometrial cancer tissues. According to gain- and loss-of-function experiments of H19, like a ceRNA, H19 elevated AXL level and HIF-1α expression so as to stimulate the migration, proliferation and EMT process of endometrial cancer. Additionally, the knockdown of H19 slowed down tumor growth, promoted apoptosis and upregulated miR-20b-5p expression but lowered the expressions of HIF-1α, PCNA and AXL in vivo. Furthermore, H19 was also verified to stimulate the activity of endometrial cancer with AXL inhibitor BGB324 in vitro and in vivo. To sum up, H19 accelerates the tumor formation of endometrial cancer through the miR-20b-5p/AXL/HIF-1α signaling pathway, thereby providing a novel target for diagnosing and treating endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Longo não Codificante/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/genética , Animais , Apoptose/genética , Benzocicloeptenos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Biologia Computacional , Neoplasias do Endométrio/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Longo não Codificante/genética , RNA Interferente Pequeno , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Transplante Heterólogo , Triazóis/farmacologia , Receptor Tirosina Quinase Axl
15.
Molecules ; 23(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071657

RESUMO

An efficient direct C(sp3)⁻H oxidation of diarylmethanes has been demonstrated by this study. This method employs environment-friendly O2 as an oxidant and is promoted by commercially available MN(SiMe3)2 [M = K, Na or Li], which provides a facile method for the synthesis of various diaryl ketones in excellent yields. This protocol is metal-free, mild and compatible with a number of functional groups on substrates.


Assuntos
Metano/química , Cetonas/química , Estrutura Molecular , Oxirredução
16.
Artigo em Inglês | MEDLINE | ID: mdl-29527188

RESUMO

Lycium barbarum L. (LBL) has beneficial effects on gestational diabetes mellitus (GDM) but the related mechanism remains unclear. Polysaccharides of LBL (LBLP) are the main bioactive components of LBL. miR-33, ATP-binding cassette transporter A1 (ABCA1) and sterol regulatory element-binding transcription 1 (SREBF1) affect lipid profiles, which are associated with GDM risk. LBLP may exert protective against GDM by affecting these molecules. Four LBLP fractions: LBLP-I, LBLP-II, LBLP-III, and LBLP-IV were isolated from LBL and further purified by using DEAE-Sephadex column. The effects of purified each fraction on pancreatic beta cells were comparatively evaluated. A total of 158 GDM patients were recruited and randomly divided into LBL group (LG) and placebo group (CG). miR-33 levels, lipid profiles, insulin resistance and secretory functions were measured. The association between serum miR-33 levels and lipid profiles were evaluated by using Spearman's rank-order correlation test. After 4-week therapy, LBL reduced miR-33 level, insulin resistance and increased insulin secretion of GDM patients. LBL increased the levels of ABCA1, high-density lipoprotein cholesterol (HDL-C) and reduced miR-33, SREBF1, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and malondialdehyde. Homeostatic model assessment of ß-cell function and insulin resistance was lower in LG than in CG, whereas homeostatic model assessment of ß-cell function and insulin secretory function was higher in LG than in CG. There was a strong positive association between miR-33 level and TG, or TC and or LDL-C, and a strong negative association between miR-33 level and HDL-C. The levels of miR-33 had negative relation with ABCA1 and positive relation with SREBF1. ABCA1 has negative relation with TG, TC, and LDL-C and positive relation with HDL-C. Inversely, SREBF1 had positive relation with TG, TC, and LDL-C and negative relation with HDL-C. The main bioactive compound LBLP-IV of LBL increased insulin secretion of beta cells and the levels of ABCA1, and reduced miR-33 levels and SREBF1 in beta cells. However, LBLP-IV could not change the levels of these molecules anymore when miR-33 was overexpressed or silenced. LBLP-IV had the similar effects with LBL on beta cells while other components had no such effects. Thus, LBLP-IV from LBL improves lipid profiles by upregulating ABCA1 and downregulating SREBF1 via miR-33.

17.
Fetal Pediatr Pathol ; 37(1): 38-48, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29336643

RESUMO

OBJECTIVES: This study evaluated the feasibility of measuring the fetal mesencephalon and pons by ultrasonographic cross sectional imaging to detect fetal central nervous system developmental abnormalities. MATERIALS AND METHODS: Fetal ultrasonographic measurements included: Fetal mesencephalon anteroposterior diameters (MAD), mesencephalon transverse diameters (MTD), pons anteroposterior diameter (PAD) and proximal transverse diameters (PTD). RESULTS: Nine-hundred ninety fetuses were imaged. Thirty-eight fetuses (observation group) presented central nervous system abnormalities; 952 fetuses without imaged abnormalities were utilized as the reference (control) group. Fetal MAD, MTD, PAD, and PTD in control fetuses showed a linear correlation with gestational age. Thirty-eight fetuses had 40 abnormal measurements (8 MAD, 8 MTD, 14 PAD, and 10 PTD), 16 in mesencephalon, and 24 in pons. All data fell below the 95% confidence intervals' lower limits for the corresponding gestational age. CONCLUSION: Using normative data based on 957 fetuses allows detection of size abnormalities of the pons and midbrain during fetal life.


Assuntos
Feto/diagnóstico por imagem , Mesencéfalo/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Neuroimagem/métodos , Ponte/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Humanos
18.
Cancer Biomark ; 21(2): 455-460, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29125482

RESUMO

OBJECTIVE: Cervical squamous cell carcinoma seriously threats to patient's life and health. MiRNAs have role of regulating cell growth, proliferation, and death. MiRNAs can promote or inhibit cell growth and proliferation. This study discussed the role of miRNA373 in regulating cervical squamous cell carcinoma growth, proliferation, and apoptosis. PATIENTS AND METHODS: MiRNA373 and scramble miRNA were synthetized and transfected to cervical squamous cell carcinoma SiHa cells by lipofectamine. IAPs plasmid and miRNA373 were sequentially transfected to SiHa cells. MTT assay, caspase-3 activity, and flow cytometry were applied to test miRNA373 and IAPs impacts on cell growth, proliferation, and apoptosis. Western blot was adopted to determine IAPs expression. RESULTS: MiRNA373 transfection obviously reduced SiHa cell growth, induced phosphatidylserine eversion and caspase-3 activation, and declined IAPs expression. IAPs interference significantly enhanced miRNA373 induced SiHa cell apoptosis. IAPs overexpression markedly restrained miRNA373 induced SiHa cell apoptosis. CONCLUSIONS: MiRNA373 transfection suppressed SiHa cell growth and proliferation. MiRNA373 induced SiHa cell apoptosis possibly through downregulating IAPs, suggesting that IAPs might be a target for cervical squamous cell carcinoma treatment.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Apoptose/genética , Carcinoma de Células Escamosas/patologia , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Transfecção , Neoplasias do Colo do Útero/patologia
19.
Exp Ther Med ; 14(1): 127-130, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672902

RESUMO

The aim of the present study was to investigate the effect of rutin treatment on the expression of glycogen synthase kinase (GSK)-3ß and tumor necrosis factor (TNF)-α in A549 human lung carcinoma cells. The A549 cells were divided into control, cisplatin and rutin (low, middle and high) groups. ELISA and western blot analysis of TNF-α expression, 4',6-diamino-2-phenylindole (DAPI) staining and GSK-3ß immunofluorescence staining were used to investigate the effect of rutin in the human lung carcinoma cells, using cisplatin as a positive control. TNF-α expression was significantly higher in the rutin and cisplatin groups compared with the control group. Additionally, DAPI staining revealed that the number of apoptotic cells was higher in the rutin and cisplatin groups compared with the control group, and immunofluorescence showed that the expression of GSK-3ß in the cisplatin and rutin groups was significantly higher compared with that in the control group. The results of the present study suggest that rutin promotes the TNF-α-induced apoptosis of A549 human lung carcinoma cells. Furthermore, rutin may be able to regulate the expression of GSK-3ß protein in these cells.

20.
Oncotarget ; 8(18): 29823-29832, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28415735

RESUMO

In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex. In vivo, Salicylate ●Phenanthroline Copper (II) Complex administration significantly attenuated tumor growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and survivin were reduced as measured by immunohistochemical staining. These data suggest that Salicylate ●Phenanthroline Copper (II) Complex is a promising novel therapeutic drug for triple-negative breast cancer and warrants further study.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Fenantrolinas/farmacologia , Salicilatos/farmacologia , Animais , Antineoplásicos/química , Apoptose/genética , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Compostos Organometálicos/química , Fenantrolinas/química , Salicilatos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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