Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Br J Radiol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775639

RESUMO

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: 46 TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, color Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesion were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analysis identified that extrathyroidal extension (OR, 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥ 14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: p = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm)+2.957 × (if aspect ratio≥0.91)+2.819 × (if extra-thyroidal extension)]. The prediction model had a good discrimination performance for TCPTC: the AUC, sensitivity and specificity were 0.928, 0.848 and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923 and 0.926. CONCLUSION: Ultrasound has potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extrathyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful to predict TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC were supplements to preoperative cytological diagnosis and molecular diagnosis on PTC subtypes.

2.
Transl Cancer Res ; 12(6): 1441-1451, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37434687

RESUMO

Background: Breast cancer (BC) is one of the most common fatal cancers in women. Identifying new biomarkers is thus of great significance for the diagnosis and prognosis of BC. Methods: In this study, 1,030 BC cases from The Cancer Genome Atlas (TCGA) were obtained for differential expression analysis and Short Time-series Expression Miner (STEM) analysis to identify characteristic BC development genes, which were further divided into upregulated and downregulated genes. Two predictive prognosis models were both defined by Least Absolute Shrinkage and Selection Operator (LASSO). Survival analysis and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic and prognostic capabilities of the two gene set model scores, respectively. Results: Our findings from this study suggested that both the unfavorable (BC1) and favorable (BC2) gene sets are reliable biomarkers for the diagnosis and prognosis of BC, although the BC1 model presents better diagnostic and prognostic value. Associations between the models and M2 macrophages and sensitivity to Bortezomib were also found, indicating that unfavorable BC genes are significantly involved in the tumor immune microenvironment. Conclusions: We successfully established one predictive prognosis model (BC1) based on characteristic gene sets of BC to diagnose and predict the survival time of BC patients using a cluster of 12 differentially expressed genes (DEGs).

3.
Clin Exp Immunol ; 211(1): 46-56, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36610698

RESUMO

Glucose 6-phosphate isomerase (G6PI) is an indicator to assist in diagnosis of rheumatoid arthritis (RA) and monitor the disease. It also plays a key role in proliferating RA synovial tissues, pannus formation, and invasion and destruction of articular cartilage. In this study, we synthesized nanoparticles targeting G6PI (siG6PI-MSN) using mesoporous silica nanocarriers (MSN) and small interfering RNA (siRNA), followed by identifying the characteristics and functions, and preliminarily exploring their application in the treatment of RA in vivo with a type II collagen-induced arthritis (CIA) rat model. It showed that the synthetic functionalized carrier had a regular pore structure and a specific volume and surface area. No obvious hemolysis or toxicity of the carrier was found when its concentration was below 100 µg/ml. Cytological results in vitro suggested that siG6PI-MSN significantly inhibited G6PI expression and reduced the ability of proliferation, migration, and invasion of FLSs, compared with the siNC-MSN group. In vivo results in the CIA rat model showed that the arthritis index and degree of joint swelling among rats in the siG6PI-MSN-treatment group were significantly lower than those in the control group. Moreover, the number of FLSs in Synovium and the levels of TNF α and IL-1 ß were also significantly decreased in the siG6PI-MSN group. Histopathology of the synovial tissue and cartilage revealed siG6PI-MSN treatment significantly reduced the pathological manifestations of arthritis. In conclusion, siG6PI-MSN effectively suppresses the proliferation and invasive growth of synovial tissue and improve joint swelling and inflammatory infiltration, thereby preventing joint damage in RA. This carrier may be a new therapeutic measure for RA, with potential social and economic benefits.


Assuntos
Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Animais , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/patologia , Movimento Celular , Glucose-6-Fosfato Isomerase/metabolismo , Glucose-6-Fosfato Isomerase/farmacologia , RNA Interferente Pequeno/metabolismo , Membrana Sinovial/metabolismo
4.
Chin J Integr Med ; 29(3): 224-232, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35809177

RESUMO

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION: CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , Células HeLa , Células-Tronco Neoplásicas/metabolismo , RNA Interferente Pequeno/metabolismo , Neoplasias do Colo do Útero/metabolismo
5.
J Refract Surg ; 38(10): 632-640, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36214348

RESUMO

PURPOSE: To compare the visual quality, accommodation, and stereoacuity between patients with a myopia magnitude of -3.00 to -8.50 diopters (D) who underwent ICLV4c (STAAR Surgical) implantation and small incision lenticule extraction (SMILE). METHODS: The visual quality parameters, amplitude of accommodation (AMP), and stereoacuity were compared between and within the ICLV4c and SMILE groups (40 eyes/group) with a mean spherical equivalent (SE) of -6.14 D. Differences in these parameters before and after surgery were analyzed using SPSS 22.0 software (SPSS, Inc). RESULTS: Modulation transfer function (MTF) cut-off increased significantly by 3.24 cycles/degree (t = -2.111, P = .041) and AMP decreased significantly by 1.66 D (t = 7.519, P < .001) from baseline to 3 months after surgery in the ICLV4c group. However, the MTF cut-off was significantly lower (t = 2.123, P = .037) and the AMP was significantly better (t = -3.605, P = .001) in the SMILE group than in the ICLV4c group at 3 months postoperatively. Other parameters such as Objective Scatter Index, Strehl ratio, and Optical Quality Analysis System (Visiometrics) under different contrast values did not show significant changes (P > .05). Stereoacuity did not improve significantly, except in a patient with anisometropia (2.50 D) in the ICLV4c group. CONCLUSIONS: The ICLV4c implantation yielded a better visual quality but worse AMP than did SMILE in patients with a myopia magnitude of -3.00 to -8.50 D in the short term. [J Refract Surg. 2022;38(10):632-640.].


Assuntos
Acomodação Ocular , Miopia , Acuidade Visual , Acomodação Ocular/fisiologia , Humanos , Miopia/fisiopatologia , Miopia/cirurgia , Índice de Gravidade de Doença , Resultado do Tratamento , Acuidade Visual/fisiologia
6.
World J Clin Cases ; 10(15): 4761-4775, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35801059

RESUMO

BACKGROUND: Gastric cancer is a leading cause of cancer-related mortality worldwide. Many somatic mutations have been identified based on next-generation sequencing; they likely play a vital role in cancer treatment selection. However, next-generation sequencing has not been widely used to diagnose and treat gastric cancer in the clinic. AIM: To test the mutant gene frequency as a guide for molecular diagnosis and personalized therapy in gastric cancer by use of next-generation sequencing. METHODS: We constructed a panel of 24 mutant genes to detect somatic nucleotide variations and copy number variations based on a next-generation sequencing technique. Our custom panel included high-mutation frequency cancer driver and tumour suppressor genes. Mutated genes were also analyzed using the cBioPortal database. The clinical annotation of important variant mutation sites was evaluated in the ClinVar database. We searched for candidate drugs for targeted therapy and immunotherapy from the OncoKB database. RESULTS: In our study, the top 16 frequently mutated genes were TP53(58%), ERBB2(28%), BRCA2 (23%), NF1 (19%), PIK3CA (14%), ATR (14%), MSH2 (12%), FBXW7 (12%), BMPR1A (12%), ERBB3 (11%), ATM (9%), FGFR2 (8%), MET (8%), PTEN (6%), CHD4 (6%), and KRAS (5%). TP53 is a commonly mutated gene in gastric cancer and has a similar frequency to that in the cBioPortal database. 33 gastric cancer patients (51.6%) with microsatellite stability and eight patients (12.5%) with microsatellite instability-high were investigated. Enrichment analyses demonstrated that high-frequency mutated genes had transmembrane receptor protein kinase activity. We discovered that BRCA2, PIK3CA, and FGFR2 gene mutations represent promising biomarkers in gastric cancer. CONCLUSION: We developed a powerful panel of 24 genes with high frequencies of mutation that could detect common somatic mutations. The observed mutations provide potential targets for the clinical treatment of gastric cancer.

7.
Chemosphere ; 303(Pt 2): 134999, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35595105

RESUMO

Although microplastic (MP) pollution has been defined as a new global challenge by the United Nations Environment Programme, their abundance and composition has only been studied in-depth within farmland soil, while minimal attention has been placed on urban soil contamination. Accordingly, within the current study, MP abundance and composition is investigated within urban soil from green spaces in Nanjing, eastern China. The average MP abundance in soil was 461 ± 222 items/kg and primarily comprised fibers (39.1%) and fragments (37.7%). MPs <1000 µm in size accounted for 83.7% of the total content and white MPs were the most abundant (26.5%). The dominant polymers were polyethylene glycol terephthalate (32.0%) and polypropylene (20.5%). Moreover, relationship network analysis generated three distinct MP modules based on community similarity. Indeed, the degree of similarity increased by ∼26.8% per kilometer. Furthermore, application of a forward selective optimal multiple regression model identified clay, sand, longitude, and points of interest for recycling bins (RecyclePOI) as the primary spatial and soil environmental factors affecting MP abundance and composition. Additionally, five potential sources of MPs were identified based on the MP diversity integrated index fitting results, and point of interest density (MDII-POI) source analysis (R2 = 0.21-0.62; P < 0.05). In particular, the point of interest of express delivery points (ExpressPOI) were important sources of plastic emissions as they are widely distributed throughout urban and fringe areas. Collectively, the findings of this study provide novel insights regarding quantitative source appointment and regional ecological control of MPs in urban soil.


Assuntos
Microplásticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Plásticos , Solo , Poluentes Químicos da Água/análise
8.
Curr Med Sci ; 42(2): 304-316, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35391619

RESUMO

OBJECTIVE: To determine the impact of smoking on disease-specific health care utilization and medical costs in patients with chronic non-communicable diseases (NCDs). METHODS: Participants were middle-aged and elderly adults with chronic NCDs from a prospective cohort in China. Logistic regressions and linear models were used to assess the relationship between tobacco smoking, health care utilization and medical costs. RESULTS: Totally, 1020 patients with chronic obstructive pulmonary disease (COPD), 3144 patients with coronary heart disease (CHD), and 1405 patients with diabetes were included in the analysis. Among patients with COPD, current smokers (ß: 0.030, 95% CI: -0.032-0.092) and former smokers (ß: 0.072, 95% CI: 0.014-0.131) had 3.0% and 7.2% higher total medical costs than never smokers. Medical costs of patients who had smoked for 21-40 years (ß: 0.028, 95% CI:-0.038-0.094) and ≥41 years (ß: 0.053, 95% CI: -0.004ß0.110) were higher than those of never smokers. Patients who smoked ≥21 cigarettes (ß: 0.145, 95% CI: 0.051-0.239) per day had more inpatient visits than never smokers. The association between smoking and health care utilization and medical costs in people with CHD group was similar to that in people with COPD; however, there were no significant associations in people with diabetes. CONCLUSION: This study reveals that the impact of smoking on health care utilization and medical costs varies among patients with COPD, CHD, and diabetes. Tobacco control might be more effective at reducing the burden of disease for patients with COPD and CHD than for patients with diabetes.


Assuntos
Doença das Coronárias , Diabetes Mellitus , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Doença das Coronárias/epidemiologia , Doença das Coronárias/terapia , Diabetes Mellitus/epidemiologia , Humanos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Fumar Tabaco
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(12): 1325-1331, 2021 Dec 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35232900

RESUMO

OBJECTIVES: Epigallocatechin gallate (EGCG) is the main bioactive component of polyphenols in tea, which has a variety of biological effects. The neurologic injury caused by cerebral ischemia/reperfusion (I/R) is closely related to the inflammatory reaction. The pro-inflammatory factor interleukin-1ß (IL-1ß) and the anti-inflammatory factor interleukin-10 (IL-10) play important roles in the regulation of inflammatory reaction. This study aims to explore the effect of EGCG on water content, myeloperoxidase (MPO) activity, IL-1ß and IL-10 in brain tissues of rats suffered cerebral I/R injury. METHODS: Middle cerebral artery occlusion model of SD rats was established by suture embolic method. After ischemia for 1.5 h, the nylon thread was pulled out and reperfusion was performed for 24.0 h. SD rats were randomly divided into 5 groups: a sham group, an I/R group, a EGCG1 group (I/R+12.5 mg/kg EGCG), a EGCG2 (I/R+25.0 mg/kg EGCG), and a EGCG3 group (I/R+50.0 mg/kg EGCG). The sham group was the same as the I/R group except that the middle cerebral artery was not blocked. The water content in brain tissues of rats was measured by dry and wet weight method, and MPO activity was detected by colorimetry. The levels of IL-1ß and IL-10 mRNA were determined by RT-PCR, and the contents of IL-1ß and IL-10 were determined by ELISA. In addition, primary cultured cortical neurons of SD rats were randomly divided into 3 groups: a control group, an oxygen-glucose deprivation/reperfusion (OGD/R) group, and an OGD/R+EGCG group (OGD/R+50.0 µmol/L EGCG). The effects of EGCG on the levels of IL-1ß and IL-10 protein in neurons were assessed by Western blotting. RESULTS: Compared with the sham group, water content, MPO activity, the contents of IL-1ß and IL-10 were significantly increased (P<0.05 or P<0.01), the mRNA expression of IL-1ß and IL-10 were obviously up-regulated (both P<0.01) in cerebral tissues of rats in the I/R group. Compared with the I/R group, water content and MPO activity in cerebral tissues of rats were significantly decreased (both P<0.01), the content of IL-1ß (P<0.01) were significantly decreased and IL-10 (P<0.01) were significantly increased in the EGCG3 group. Compared with the I/R group, the mRNA expression of IL-1ß was obviously down-regulated and the mRNA expression of IL-10 was obviously up-regulated in the EGCG2 and the EGCG3 group (P<0.05 or P<0.01). Compared with the control group, the protein levels of IL-1ß and IL-10 in neurons were significantly increased in the OGD/R group (both P<0.01). Compared with the OGD/R group, the protein expression of IL-1ß was obviously down-regulated and the protein expression of IL-10 was obviously up-regulated in neurons in the OGD/R+EGCG group (both P<0.01). CONCLUSIONS: EGCG can inhibit the inflammatory reaction induced by cerebral I/R, which may be related to down-regulating the expression of pro-inflammatory factor IL-1ß and up-regulating anti-inflammatory factor IL-10.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/tratamento farmacológico , Catequina/análogos & derivados , Infarto da Artéria Cerebral Média , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
11.
J Cell Mol Med ; 24(19): 11381-11396, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32844595

RESUMO

Inflammatory cytokine-induced cell apoptosis is important for initiation and progression of chronic heart failure (CHF). Non-coding RNAs, including long non-coding RNAs and microRNAs, have emerged as critical regulators of this pathological process. The role in regulating inflammation and induction to cell apoptosis in CHF is not well understood. This study found CHF patients had elevated serum miR-939-5p, with greater increase in New York Heart Association (NYHA) I-II patients than in NYHA III-IV. Moreover, miR-939-5p was positively correlated with B-type natriuretic peptide (BNP) in NYHA III-IV patients, while not in NYHA I-II. Further study showed miR-939-5p mimics promoted cell proliferation and inhibited inflammatory cytokine-induced apoptosis of HUVECs and H9C2, while inhibition of endogenous miR-939-5p produced the opposite effects. Induced nitric oxide synthase (iNOS) and tumour necrosis factor α (TNFα) were identified as target genes of miR-939-5p. Additionally, lncRNA-NOS2P3 acted as an endogenous sponge RNA to inhibit miR-939-5p expression, regulate the expression of iNOS/TNFα and control inflammation-induced cells apoptosis. These suggest that CHF patients exhibited elevated serum miR-939-5p level especially in NYHA I-II grades. And lnc-NOS2P3-miR-939-5p-iNOS/TNFα pathway regulated inflammatory cytokine-induced endothelial and myocardial cells apoptosis and provided a promising strategy for diagnosis and treatment of CHF.


Assuntos
Apoptose , Regulação da Expressão Gênica , Insuficiência Cardíaca/genética , Células Endoteliais da Veia Umbilical Humana/patologia , MicroRNAs/genética , Miocárdio/patologia , RNA Longo não Codificante/genética , Transdução de Sinais , Apoptose/genética , Sequência de Bases , Doença Crônica , Citocinas/metabolismo , Insuficiência Cardíaca/sangue , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , MicroRNAs/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-32714413

RESUMO

OBJECTIVE: To explore whether Chuang Ling Ye (CLY), a traditional Chinese herbal medicine compound, could improve the treatment of idiopathic granulomatous mastitis (IGM) via decreasing inflammatory response. METHODS: Herein, 40 patients with IGM who had wounds requiring dressing change were enrolled and randomly divided into two groups: the CLY group and the control group. The size of the neoplasm and pain score of patients were followed-up for 4 weeks. Local tissues were taken during dressing change and examined by commercial enzyme-linked immunosorbent assay (ELISA) kits. The levels of inflammatory markers, including interleukin-1ß (IL-1ß), IL-2, IL-6, interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) were measured. RESULTS: After treatment, the size of the neoplasm in the CLY group was significantly smaller than that in the control group (14.28 cm ± 8.96 cm vs. 21.14 cm ± 0.12 cm, P=0.038), and the pain scores were markedly reduced (P=0.004). Besides, CLY downregulated the expression levels of IL-1ß, IFN-γ, and TNF-α. CONCLUSION: External use of CLY could reduce the neoplasm of IGM by inhibiting local inflammation. This trial is registered with ChiCTR1800017744.

13.
J Biol Chem ; 295(22): 7653-7668, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32321761

RESUMO

The erythropoietin-producing human hepatocellular receptor EPH receptor B6 (EPHB6) is a receptor tyrosine kinase that has been shown previously to control catecholamine synthesis in the adrenal gland chromaffin cells (AGCCs) in a testosterone-dependent fashion. EPHB6 also has a role in regulating blood pressure, but several facets of this regulation remain unclear. Using amperometry recordings, we now found that catecholamine secretion by AGCCs is compromised in the absence of EPHB6. AGCCs from male knockout (KO) mice displayed reduced cortical F-actin disassembly, accompanied by decreased catecholamine secretion through exocytosis. This phenotype was not observed in AGCCs from female KO mice, suggesting that testosterone, but not estrogen, contributes to this phenotype. Of note, reverse signaling from EPHB6 to ephrin B1 (EFNB1) and a 7-amino acid-long segment in the EFNB1 intracellular tail were essential for the regulation of catecholamine secretion. Further downstream, the Ras homolog family member A (RHOA) and FYN proto-oncogene Src family tyrosine kinase (FYN)-proto-oncogene c-ABL-microtubule-associated monooxygenase calponin and LIM domain containing 1 (MICAL-1) pathways mediated the signaling from EFNB1 to the defective F-actin disassembly. We discuss the implications of EPHB6's effect on catecholamine exocytosis and secretion for blood pressure regulation.


Assuntos
Glândulas Suprarrenais/enzimologia , Catecolaminas/metabolismo , Células Cromafins/enzimologia , Exocitose , Receptor EphB6/metabolismo , Transdução de Sinais , Glândulas Suprarrenais/citologia , Animais , Catecolaminas/genética , Células Cromafins/citologia , Efrina-B1/genética , Efrina-B1/metabolismo , Feminino , Masculino , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Receptor EphB6/genética , Caracteres Sexuais , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
14.
J Cancer ; 10(21): 5244-5255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602275

RESUMO

We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-ß combined with TNF-α) and its potential mechanism. Our results showed that BrMC inhibited lung cancer stemness, as validated by enhanced self-renewal ability, higher in vitro tumorigenicity, and increased expression of CD133, CD44, Bmi1 and Oct4 in H460 cells administered TNF-α after prolonged induction by TGF-ß, in a concentration-dependent manner. Both NF-κB inhibition by SN50 and FoxM1 suppression by thiostrepton (THI) prompted the inhibition of BrMC on lung CSCs. Conversely, overexpression of NF-κBp65 significantly antagonized the above effects of BrMC. Meanwhile, overexpression of FoxM1 also significantly compromised BrMC function on suppression of FoxM1 and NF-κBp65 as well as stemness of lung CSCs. Our results suggest that activation of NF-κB and FoxM1 by cytokines facilitate the acquisition CSCs phenotype, and compromise the chemical inhibition, which may represent an effective therapeutic target for treatment of human lung cancer. Moreover, BrMC may be a potential promising candidate for targeting NF-κB/ FoxM1 to prevent the tumorigenesis under inflammatory microenvironment.

15.
AAPS PharmSciTech ; 20(7): 289, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414349

RESUMO

The aim of this study was to evaluate the use of a novel porous silica carrier, AEROPERL® 300 Pharma (AP), to improve the in vitro release and oral bioavailability of puerarin (PUE) in solid dispersions (SDs). PUE-AP SD formulations with different ratios of drug to silica (RDS) were prepared by the solvent method. The scanning electron microscopy (SEM) results indicated that the dispersion of PUE improved as the concentration of AP was increased. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed that PUE mostly existed in an amorphous state in the SDs. The rate of drug dissolution from the SDs was significantly higher than that from the PUE powder (p < 0.05). The in vitro drug release percentage from the PUE-AP SDs increased as the RDS was reduced. The oral bioavailability of PUE from the SDs improved when using AP, as indicated by AUC(0-∞), which was 2.05 and 2.01 times greater than that of the PUE (API) and PVP K30 SDs, respectively (p < 0.05). The drug content, in vitro release profiles, and the amorphous state of PUE in the PUE-AP SDs showed no significant changes after being stored at room temperature for 6 months or under accelerated conditions (40 ± 2°C, 75 ± 5% relative humidity) for 3 months. AP has a high pore volume, large specific surface area, excellent flowability, and hydrophilic properties, making it capable of improving the dissolution and bioavailability of poorly water-soluble drugs.


Assuntos
Portadores de Fármacos , Isoflavonas/administração & dosagem , Dióxido de Silício/química , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas , Isoflavonas/farmacocinética , Masculino , Microscopia Eletrônica de Varredura , Porosidade , Povidona/química , Difração de Pó , Ratos , Ratos Sprague-Dawley , Solubilidade
16.
World J Pediatr ; 14(4): 344-349, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29948966

RESUMO

BACKGROUND: To investigate the clinical features of necrotizing pneumonia (NP) caused by refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: A retrospective observational study was carried out in patients with NP caused by RMPP who were admitted to our hospital from January 2008 to December 2015, and the clinical manifestations, laboratory data, imaging performances, hospital courses and outcomes were analyzed. RESULTS: Twenty-five patients with NP caused by RMPP were collected, with a median age of 5.1 (4.0-7.9) years. The mean duration of fever and hospital stay was 21.0 ± 8.9 and 19.9 ± 9.9 days, respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein, interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the pleural fluid cell count, LDH and protein were also increased. 80.0% of the patients had pleural effusion; and a high incidence of lobar atelectasis and pulmonary consolidation was found the patients. The mean duration from the onset of symptoms to the discovery of necrotic lesions was 21.0 ± 6.9 days. 80.0% of the patients were administrated corticosteroids, and bronchoalveolar lavage was extracted separately from all patients. Of the 20 patients who presented with pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest drainage. All patients received prolonged courses of antibiotics (32.2 ± 8.7 days). All patients were dischaged home and recovered without surgical intervention; and chest lesions were resolved or only minimal residual fibrotic changes were residual within 3.0 (2.0-6.0) months. CONCLUSIONS: Necrotizing pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good outcomes can be achieved with appropriate management.


Assuntos
Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Mycoplasma/patogenicidade , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/patologia , Biomarcadores/sangue , Broncoscopia/métodos , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos , Humanos , L-Lactato Desidrogenase/sangue , Tempo de Internação , Masculino , Necrose/patologia , Pneumonia por Mycoplasma/epidemiologia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Pak J Pharm Sci ; 31(3(Supplementary)): 1087-1092, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731448

RESUMO

To evaluate the effectiveness of epigallocatechin gallate (EGCG) in inhibiting corneal neovascularization in rat alkaline burn model. Corneal neovascularization model was induced by sodium hydroxide alkaline burn injury in SD rats. Rats were randomly divided into two groups and were given intraperitoneal injection with EGCG or PBS per day for up to 14 days respectively. Corneal inflammation and neovascularization area were assessed on days 3, 7, and 14 after cauterization with digital photographs. Vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) mRNA levels were measured by reverse transcription-polymerase chain reaction (qRT-PCR). The nuclear transfactor-Κb (NF-κB) subunit P65 protein was assayed by immunohistochemistry. The differences of corneal inflammation scores between two groups were significant. The area of CNV between two groups had no significant difference on day 3 but have significant difference on days 7 and 14.The PDEF mRNA expression in EGCG group was significantly higher and the expression of VEGF mRNA was lower than those in PBS group. The results of immunohistochemistry showed from day 7, expression of NF-κB P65protein was suppressed considerably in EGCG group. This study demonstrates that EGCG inhibits corneal neovascularization in a rat model induced by alkali burn.


Assuntos
Catequina/análogos & derivados , Neovascularização da Córnea/prevenção & controle , Animais , Queimaduras Químicas/fisiopatologia , Catequina/farmacologia , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Neovascularização da Córnea/fisiopatologia , Proteínas do Olho/biossíntese , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , Proteínas de Neoplasias/metabolismo , Fatores de Crescimento Neural/biossíntese , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ratos , Serpinas/biossíntese , Hidróxido de Sódio , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/biossíntese
18.
PLoS One ; 12(7): e0181396, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28753619

RESUMO

OBJECTIVES: To provide an empirical examination of patient-provider relationships (PPR) and its association with organizational and individual factors. METHODS: A national cross-sectional survey was conducted by stratified cluster sampling in 77 hospitals across seven provinces in China between July 2014 and April 2015, involving 3621 doctors, 5561 nurses, and 8022 patients with response rates of 62.93%, 61.16%, and 33.08%, respectively. Self-perceived PPR was the outcome variable. Organizational factors included hospital type (western medicine [WM] and traditional Chinese medicine [TCM] hospital); hospital level (tertiary and secondary hospital); area of specialization (internal medicine and surgery); ratio of doctors (nurses) to ward beds; doctors/nurses' concerns about performance assessment; and patients' perceptions of healthcare cost. Individual factors included consultation, listening to patients and socio-demographic factors. RESULTS: 54.6% of doctors, 36.6% of nurses, and 10.2% of patients perceived PPR as poor. Organizational factors independently associated with providers' perception of poor PPR included hospital type (WM vs TCM: OR = 1.25 [95% CI: 1.06-1.47]) and concerns about performance assessment (high vs low levels: OR = 1.40 [95% CI: 1.14-1.72]) for doctors, and concerns about performance assessment (average vs low levels: OR = 0.79 [95% CI: 0.67-0.93]) for nurses. Those associated with patients' perception of poor PPR included hospital type (WM vs TCM: OR = 0.63 [95% CI: 0.53-0.74]) and hospital level (tertiary vs secondary: OR = 0.65 [95% CI: 0.51-0.82]). Doctors and nurses reporting listening to patients "frequently" had better perceptions of PPR (OR = 0.46 [95%CI: 0.38-0.56] and 0.49 [95% CI: 0.41-0.59] for doctors and nurses, respectively), as did their patients (OR = 0.24 [95% CI: 0.18-0.31] and 0.54 [95% CI: 0.35-0.84] for doctors and nurses, respectively). CONCLUSIONS: Although our findings require validation in different organizational settings given the likely variability of these associations across systems, our results suggest that implementing moderate levels promoting the level of medical treatment, and broadening doctors/nurses training regarding listening to patients, may benefit to enhance PPR.


Assuntos
Hospitais/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Pacientes/estatística & dados numéricos , Médicos/estatística & dados numéricos , China , Estudos Transversais , Humanos , Relações Profissional-Paciente , Fatores Socioeconômicos
19.
Oncotarget ; 8(22): 36696-36706, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-27852041

RESUMO

BACKGROUND: This study determined whether axillary ultrasound (AUS) accurately predicted the status of axillary lymph nodes of patients who received different number of cycles of neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: From 2008 to 2015, 656 cases of patients with breast cancers who received NAC and had subsequent axillary lymph node dissection were included in this study. The findings of preoperative AUS were tested by pathological examination. We evaluated the sensitivity, specificity and accuracy of AUS for patients who received two-, four-, and six-cycle NAC. RESULTS: In the two-cycle subgroup, the sensitivity (Sn), specificity (Sp) and diagnostic odds ratio (DOR) were 80.2% (95% CI: 74.3%-86.2%), 61.4% (95% CI: 48.8%-74.0%) and 6.64 (95% CI: 3.36-12.4) respectively. In the four-cycle subgroup, the Sn, Sp and DOR were 69.7% (95% CI: 62.2%-77.1%), 66.1% (95% CI: 53.7%-78.5%) and 4.47 (95% CI: 2.32-8.62), respectively. In the six-cycle subgroup, the Sn, Sp and DOR were 56.7% (95% CI: 49.5%-64.0%), 74.5% (95% CI: 62.8%-87.2%) and 3.83 (95% CI: 1.863-7.86), respectively. Furthermore, the patients with normal AUS findings after six cycles of NAC have few positive nodes than patients with suspicious findings (p < 0.001). CONCLUSION: Preoperative AUS is a potentially useful imaging modality to predict the pathologic status of the axillary within four cycles of NAC. Although the accuracy is lower for patients who completed six cycles of NAC than that who received four- and two- cycles, the number of positive lymph nodes for patients with normal findings on AUS is low.


Assuntos
Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Ultrassonografia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Ultrassonografia/métodos , Ultrassonografia/normas
20.
Oncol Lett ; 12(5): 3499-3505, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27900027

RESUMO

Overexpression of Notch4 is associated with a variety of tumor types. Only sparse information exists on Notch4 expression in pancreatic cancer (PC). The present study demonstrated that Notch4 expression was significantly upregulated in PC cell lines compared with a non-transformed pancreatic epithelial cell line, HPDE6c-7. To investigate the possible role of Notch4 in PC cells, an RNA interference approach was used to silence Notch4 expression. The results revealed that small interfering RNA (siRNA) targeting Notch4 significantly impeded the viability, migration and invasion abilities of PC cells in vitro. Downregulation of Notch4 with siRNA sensitized cells to the action of docetaxel. Furthermore, Notch4 downregulation enhanced the inhibition of Akt activation and the fascin expression induced by docetaxel in PC cells. Together, these data provide insight into the function of Notch4 and suggest that Notch4 may represent a new potential target for gene therapy in PC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA