Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 257
Filtrar
1.
Analyst ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724655

RESUMO

Single nucleotide polymorphisms (SNPs) have been proven to be important biomarkers for disease diagnosis, prognosis and disease pathogenesis. Here, taking the advantages of a self-assembled oligonucleotide sandwich structure and robust chemical reactions, we have developed a simple, high-throughput and effective colorimetric analytical technique termed CuAAC-based ligation-assisted assays (CuAAC-LA) for SNP detection using a DNA-BIND 96-well plate. With the 5'-azide and 3'-alkyne groups labelled on two oligonucleotide probes, the target DNA can direct a Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction. Since the small difference in duplex stability caused by a single-nucleotide mismatch was amplified by the steric effects of these reactive groups for the ligation reaction of an unstable duplex, CuAAC-LA exhibited an ultra-sensitive discrimination ability for a mutant type target in the presence of large amounts of wild type targets. As low as 0.05% SNP could be clearly detected, which was better than most previously reported methods by various DNA ligases, indicating that a simple and rapid synthetic method i.e., the DNA template-directed click reaction held the potential to replace the ligase for SNP detection.

2.
BMC Cancer ; 19(1): 1085, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718619

RESUMO

BACKGROUND: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. METHODS: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient's age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival. RESULTS: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor. CONCLUSIONS: This is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.

3.
Med Sci Monit ; 25: 8131-8141, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663517

RESUMO

BACKGROUND Worldwide, mortality from cervical cancer in women remains high. This study aimed to investigate the expression of long noncoding RNA (lncRNA) TP73-AS1, microRNA-329-3p (miRNA-329-3p), and the SMAD2 gene and their regulatory relationships in human cervical cancer tissue and cervical cancer cell lines. MATERIAL AND METHODS Cervical cancer tissue samples (n=30) and normal control cervical tissues were studied. Cell proliferation and migration were investigated in HeLa and SiHa human cervical cancer cells using the MTT assay, crystal violet staining, wound healing assay, and the transwell assay. Expression of lncRNA TP73-AS1 and the SMAD2 gene were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Enrichment of miR-329-3p was measured using the RNA immunoprecipitation assay (RIPA). Targeting relationships between TP73-AS1, miR-329-3p, and SMAD2 were identified using the dual-luciferase reporter assay. A subcutaneous xenograft model was established, tumor size was measured, and SMAD2 expression was detected using immunohistochemistry. RESULTS LncRNA TP73-AS1 was overexpressed in cervical cancer tissues and cells and was associated with reduced expression of miR-329-3p. Down-regulation of lncRNA TP73-AS1 inhibited cell proliferation, migration and invasion and increased miR-329-3p expression. Expression of SMAD2 down-regulated miR-329-3p and was associated with increased expression of TP73-AS1. LncRNA TP73-AS1 knockdown resulted in miR-329-3p silencing. In tumor xenografts, expression of TP73-AS1 reduced the tumor volume and down-regulated the expression levels of the SMAD2 gene. CONCLUSIONS LncRNA TP73-AS1 promoted proliferation of cervical cancer cell lines by targeting miR-329-3p to regulate the expression of the SMAD2 gene. A regulatory network was formed between lncRNA TP73-AS1, miR-329-3p, and SMAD2.

4.
Biosens Bioelectron ; 144: 111695, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526982

RESUMO

Epigenetic inheritance is a heritable change in gene function independent of alterations in nucleotide sequence. It regulates the normal cellular activities of the organisms by affecting gene expression and transcription, and its abnormal expression may lead to the developmental disorder, senile dementia, and carcinogenesis progression. Thus, epigenetic inheritance is recognized as an important biomarker, and the accurate quantification of epigenetic inheritance is crucial to clinical diagnosis, drug development and cancer treatment. Noncoding RNA, DNA methylation and histone modification are the most common epigenetic biomarkers. The conventional biosensors (e.g., northern blotting, radiometric, mass spectrometry and immunosorbent biosensors) for epigenetic biomarkers assay usually suffer from hazardous radiation, complicated manipulation, and time-consuming procedures. To facilitate the practical applications, some new biosensors including colorimetric, luminescent, Raman scattering spectroscopy, electrochemical and fluorescent biosensors have been developed for the detection of epigenetic biomarkers with simplicity, rapidity, high throughput and high sensitivity. In this review, we summarize the recent advances in epigenetic biomarkers assay. We classify the biosensors into the direct amplification-free and the nucleotide amplification-assisted ones, and describe the principles of various biosensors, and further compare their performance for epigenetic biomarkers detection. Moreover, we discuss the emerging trends and challenges in the future development of epigenetic biomarkers biosensors.

5.
Int J Mol Med ; 44(5): 1619-1628, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485601

RESUMO

MicroRNAs (miRNAs or miRs) play an important role in pathological processes in diabetic nephropathy (DN). This study aimed to explore whether miR­379­5p is associated with renal fibrosis in DN and to elucidate the underlying mechanisms. In vitro experiments indicated that miR­379­5p expression was downregulated by high glucose (HG) treatment in mouse mesangial cells (MMCs). Transfection with miR­379­5p mimics suppressed the proliferation and the accumulation of extracellular matrix (ECM) components, which were promoted by HG treatment. LIN28B was proven to be a direct target of miR­379­5p by luciferase report assay. In addition, the loss of expression of LIN28B, as well as the decrease in cell proliferation and in the accumulation of ECM components, which were induced by the knockdown of LIN28B, were attenuated in the MMCs following transfection with miR­379­5p inhibitors. Furthermore, type 2 diabetic db/db mice were used to examine the efficiency of miR­379­5p agomir in the alleviation of renal fibrosis. Consistent with the results of the in vitro experiments, miR­379­5p agomir suppressed mesangial cell proliferation and the accumulation of ECM components by regulating the LIN28B/let­7 pathway. Taken together, the findings of this study suggest that miR­379­5p is highly involved in renal fibrosis in DN, and that it may be a potential effective therapeutic target for DN.

6.
Int J Oncol ; 55(3): 708-720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364744

RESUMO

Long intergenic noncoding RNA 00961 (Linc00961) has been identified as a tumor suppressor in various types of cancer. However, the critical roles of Linc00961 in the carcinogenesis and progression of skin melanoma (SM) are yet to be fully elucidated. The present study revealed via reverse transcription­quantitative PCR analysis that Linc00961 was downregulated in the tissues of patients with SM compared with benign nevi, and in A375, A2058 and SK­MEL­28 cell lines compared with human melanocytes. Furthermore, overexpression of Linc00961 inhibited cell proliferation, and promoted the apoptosis of A375 and SK­MEL­28 cells in vitro and in vivo, as determined by Cell Counting Kit­8 and flow cytometry assays, and tumor xenograft studies, respectively. Overexpression of Linc00961 also led to an attenuation of the migration and invasive capabilities of A375 and SK­MEL­28 cells, measured using Transwell assays. Functionally, it was demonstrated that Linc00961 acted as a competing endogenous RNA (ceRNA) by competitively sponging microRNA­367 (miR­367) in A375 and SK­MEL­28 cells; restoration of miR­367 rescued the inhibitory effects of Linc00961 on A375 and SK­MEL­28 cells. Finally, it was observed that phosphate and tension homology deleted on chromosome 10 (PTEN), an established target of miR­367 in A375 and SK­MEL­28 cells, was positively regulated by Linc00961, and its inhibition reversed the inhibitory effects of Linc00961 on the proliferation and invasion of A375 and SK­MEL­28 cells. Collectively, the present study revealed that Linc00961 was downregulated in SM, and furthermore, Linc00961 was identified as a ceRNA that inhibits the proliferation and invasion of A375 and SK­MEL­28 cells by modulating the miR­367/PTEN axis.

7.
Cancer Med ; 8(12): 5600-5608, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31407527

RESUMO

In the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models were constructed. A nomogram was developed based on significant prognostic indicators of OS. The discriminatory and predictive capacities of the nomogram were assessed using Harrell's concordance index (C-index) and calibration plots. A total of 1651 eligible patients were identified, with a median survival time of 31 months (range 0-131 months), and the 3- and 5-year OS rates were 52.8% and 39.5%, respectively. Multivariate analysis revealed that race (P < .001), marital status (P = .011), N stage (P = .002), M stage (P < .001), hormone receptor (P < .001), human epidermal growth factor receptor-2 (HER2) (P = .001), surgery (P < .001), chemotherapy (P < .001), and radiotherapy (P = .010) were independent prognostic indicators of IBC. These nine variables were incorporated to construct a nomogram. The C-indexes of the nomogram were 0.738 (95% confidence interval [CI]: 0.717, 0.759) and 0.741 (95% CI: 0.717, 0.765) for the internal and external validations, respectively. The nomogram had a better discriminatory capacity for predicting OS than did the SEER summary stage (P < .001) or the American Joint Committee on Cancer tumor-node metastasis staging systems (8th edition; P < .001). The calibration plot revealed satisfactory agreement between the findings and predicted outcomes in both the internal and external validations. The nomogram-based 3- and 5-year OS predictions for patients with IBC exhibited superior accuracy over the existing models.

8.
Adv Exp Med Biol ; 1155: 1049-1056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468466

RESUMO

This study investigated the effects of taurine on bowel inflammation resulting from heat stress in broilers, with the intent of providing insight into potential improvement of the condition of broilers. A total of 300 healthy 1 day AA broilers were selected, fed normally until day 7, and allocated randomly to 5 treatment groups, namely, the control group(C), the heat stress group(HS), the low Tau (LTau) group, the middle Tau (MTau) group and the high Tau (HTau) group, which represent low, medium and high concentrations of taurine respectively. In the study, various concentrations of taurine were added to the drinking water. The Heat Stress model was produced by maintaining Broilers in a room at 34 °C.Heat stress persisted for 6 h, 12 h, 7 days, and 14 days. The results showed that the expression levels of TNF-α, IFN-γ, and IL-1ß of the HTau group were significantly lower than that of the HS group at all time points examined (6 h, 12 h, 7 days, and 14 days) (P < 0.05). Compared with the HS group subjected to 6 h, 12 h and 14 days of heat stress, the MTau group exhibited significantly lower degrees of TNF-α and IL-1ß expression. Moreover, the expression of IFN-γ was higher in the HS group after 6 h, 12 h and 7 days of heat stress than that of the MTau group subjected to similar times of heat stress (P < 0.05).There were no significant difference among the groups at other periods of heat stress (P > 0.05).


Assuntos
Resposta ao Choque Térmico , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Taurina/farmacologia , Animais , Galinhas , Citocinas/metabolismo , Temperatura Alta , Distribuição Aleatória
9.
Pharmacol Res ; 147: 104357, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31356863

RESUMO

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3ß-mediated ß-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.

10.
Theranostics ; 9(15): 4450-4460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285772

RESUMO

DNA alkylation and oxidation are two most common forms of cytotoxic damage with the characteristics of mutagenic and carcinogenic. Human alkyladenine DNA glycosylase (hAAG) is the only glycosylase known to repair a wide variety of alkylative and oxidative DNA lesions. However, few approaches are capable of real-time monitoring hAAG activity. Methods: Herein, we develop a facile fluorescent strategy for homogeneous and sensitive sensing of hAAG activity based on the controllable autocatalytic cleavage-mediated fluorescence recovery. The presence of hAAG enables the cleavage of hairpin probe 1 (HP1) at the damaged 2'-deoxyinosine site by AP endonuclease 1 (APE1), forming a DNA duplex. The trigger 1 built in the resultant DNA duplex may hybridize with hairpin probe 2 (HP2) to induce the T7 exonuclease (T7 exo)-catalyzed recycling cleavage of HP2 (Cycle I) to release trigger 2. The trigger 2 can further hybridize with the signal probe (a fluorophore (FAM) and a quencher (BHQ1) modified at its 5' and 3' ends) to induce the subsequent recycling cleavage of signal probes (Cycle II) to liberate FAM molecules. Through two-recycling autocatalytic cleavage processes, large amounts of fluorophore molecules (i.e., FAM) are liberated from the FAM-BHQ1 fluorescence resonance energy transfer (FRET) pair, leading to the amplified fluorescence recovery. Results: Taking advantage of the high accuracy of in vivo DNA repair mechanism, the high specificity of T7 exo-catalyzed mononucleotides hydrolysis, and the high efficiency of autocatalytic recycling amplification, this strategy exhibits high sensitivity with a detection limit of 4.9 × 10-6 U/µL and a large dynamic range of 4 orders of magnitude from 1 × 10-5 to 0.1 U/µL, and it can further accurately evaluate the enzyme kinetic parameters, screen the potential inhibitors, and even quantify the hAAG activity from 1 cancer cell. Conclusion: The proposed strategy can provide a facile and universal platform for the monitoring of DNA damage-related repair enzymes, holding great potential for DNA repair-related biochemical research, clinical diagnosis, drug discovery, and cancer therapy.

11.
Anim Biotechnol ; : 1-8, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31179830

RESUMO

MicroRNA-1 (miR-1) has been shown to play an important role in muscle growth and development, however, it was mainly discovered in model animals. To explore the function and mechanism of miR-1 in goat, we firstly explored the expression profile of miR-1 in goat tissues and cells. Furthermore, the target gene of miR-1 was predicted, and the relationship between miR-1 and one of its target genes, histone deacetylase 4 (HDAC4), was analyzed through double luciferase reporter assay, real-time PCR, and western blot. It was found that the miR-1 is most abundantly expressed in goat heart and skeletal muscle tissue. Meanwhile, the expression of miR-1 showed an increasing tendency from new-born goats to the 7-month-old goats, and then its expression decreases as the goats mature further. In addition, the expression levels of miR-1 decreased in goat skeletal muscle satellite cells with the algebraic increasing of cells. At last, the results showed that HDAC4 is a target gene of miR-1 in goat, and miR-1 can inhibit the post-transcriptional expression of HDAC4, but had no significant influence on the mRNA level of HDAC4. It was hypothesized that miR-1 promotes muscle development by inhibiting the post-transcriptional expression of HDAC4 in goat.

12.
Cancer Gene Ther ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31155611

RESUMO

Effective chimeric antigen receptor-modified T-cell (CAR-T) therapy for liver metastases (LM) will require innovative solutions to ensure efficient delivery and minimization of systemic toxicity. We previously demonstrated the safety of CAR-T hepatic artery infusions (HAI). We subsequently conducted the phase 1b HITM-SIR trial, in which six patients (pts) with CEA+ LM received anti-CEA CAR-T HAIs and selective internal radiation therapy (SIRT). The primary endpoint was safety with secondary assessments of biologic activity. Enrolled pts had a mean LM size of 6.4 cm, 4 pts had >10 LM, and pts received an average of two lines of prior systemic therapy. No grade 4 or 5 toxicities were observed, and there were no instances of severe cytokine-release syndrome (CRS) or neurotoxicity. The mean transduction efficiency was 60.4%. Following CAR-T HAI, reduced levels of GM-CSF-R, IDO, and PD-L1 were detected in LM, and serum CEA levels were stable or decreased in all subjects. Median survival time was 8 months (mean 11, range 4-31). Anti-CEA CAR-T HAI with subsequent SIRT was well tolerated, and biologic responses were demonstrated following failure of conventional therapy. HAI of CAR-T was once again confirmed not to be associated with severe CRS or neurotoxicity.

13.
Medicine (Baltimore) ; 98(24): e15982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192939

RESUMO

BACKGROUND: FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1), as a novel lncRNA, was reported to be up-regulated in various cancers and involved in tumor progression. This study systematically assessed the prognostic value of FEZF1-AS1 in solid tumors. METHODS: Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies that evaluated the prognostic role of FEZF1-AS1 expression in cancer patients. Pooled hazard ratios (HRs) and combined odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. The meta-analysis was conducted using Stata/SE 14.1. RESULTS: Fifteen original studies involving 1378 patients were enrolled. Pooled results showed that increased expression of FEZF1-AS1 significantly correlated with shorter overall survival (OS) in cancer patients (HR 2.04, 95% CI 1.60-2.47), and also shorter disease-free survival (DFS) (HR 2.08, 95% CI 1.27-2.89). Additionally, the combined ORs indicated that increased FEZF1-AS1 expression was significantly associated with lymph node metastasis (OR 3.35, 95% CI 1.98-5.67), distant metastasis (OR 3.10, 95% CI 1.86-5.15), poor tumor differentiation (OR 2.90, 95% CI 1.45-5.80), high depth of tumor invasion (OR 2.72, 95% CI 1.36-5.43), and advanced clinical stage (OR 2.76, 95% CI 1.75-4.35). Expression analysis using the Gene Expression Profiling Interactive Analysis database indicated that the expression of FEZF1-AS1 was higher in tumor tissues than that in the corresponding normal tissues. The results of survival analysis revealed that increased FEZF1-AS1 expression was correlated with poor OS and DFS in cancer patients. CONCLUSIONS: LncRNA FEZF1-AS1 may serve as a valuable prognostic biomarker for clinical outcomes in various solid tumors.


Assuntos
Neoplasias/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Neoplasias/metabolismo , Razão de Chances , Prognóstico , RNA Antissenso/biossíntese , Análise de Sobrevida , Regulação para Cima
14.
Biosci Rep ; 39(7)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31221818

RESUMO

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS). The present study explored the role of intestinal microbiota in the initiation and propagation of mice induced by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 48 C57BL/6 were randomly divided into control group and EAE group. The changes of body weight and the scores of neurological function were recorded. The mRNA expression of the receptor tyrosine kinase subfamily (AXL) was detected by real-time quantitative PCR. The levels of IL-17 and IFN-γ in blood samples were examined by ELISA. The intestinal microbial composition of mice at different time points during the EAE induction was analyzed by 16S rRNA gene-based sequencing. In EAE group, the body weight began to reduce at day 3 and neurological symptoms began to appear at day 7 after EAE induction. The levels of IL-17 and IFN-γ in EAE group reached the peak at day 21 and then decreased gradually. However, the expression of Axl and SOCS3 reached the lowest level at day 21 and then increased gradually. The microbiome analyses revealed that the abundances of Alistipes, Blautia, and Lachnospiraceae_NK4A136_group were significantly changed at day 14, whereas the abundances of Allobaculum, Eubacterium and Helicobacter were significantly changed at day 30 of EAE induction. The prevotellaceae_NK3B31_group may be key bacteria that contribute to the development of MS. Regulation of intestinal microbiota composition can become a new therapeutic target for the treatment of MS.

15.
Zhongguo Gu Shang ; 32(5): 462-468, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31248244

RESUMO

OBJECTIVE: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA. METHODS: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment. RESULTS: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group(P<0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group(P>0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group(P<0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference(P>0.05); there was significant difference between needle knife group and model group(P<0.05); there was no significant difference between electro-acupuncture group and needle-knife group(P>0.05). In gait change, there was significant difference between model group and electro-acupuncture group(P<0.05); there was no significant difference between needle-knife group and model group(P>0.05). In joint activity, there was significant difference between electro-acupuncture group and model group(P<0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group(P<0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group(P>0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly(P<0.01), the ultimate load of the electro-acupuncture group decreased(P>0.05), and the ultimate load of the needle-knife group increased(P>0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly(P<0.05), and the ultimate load of the needle-knife group increased significantly (P<0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased(P>0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly(P<0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased(P>0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased(P>0.05), and the maximum displacement of the needle-knife group increased significantly(P<0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased(P>0.05). There was no significant difference in stiffness among groups(P>0.05). CONCLUSIONS: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA.


Assuntos
Eletroacupuntura , Osteoartrite do Joelho , Animais , Humanos , Articulação do Joelho , Masculino , Músculo Quadríceps , Coelhos , Ratos , Tendões
16.
Biosci Rep ; 39(6)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31085718

RESUMO

The specific functions and clinical significance of miR-940 in endometrial carcinoma (EC) have not been studied. First, we assessed the expression of miR-940 and MRVI1 in EC tissues collected from The Cancer Genome Atlas (TCGA) database and EC cell lines. miR-940 was significantly overexpressed in EC tissues and cell lines, particularly in RL95-2 cells. Correlation analysis showed that miR-940 expression level was remarkably associated with age, grade, and death. Moreover, the overall survival (OS) rate in the miR-940 low expression group was higher, compared with miR-940 high expression group. Univariate and multivariate models demonstrated that miR-940 expression, stage, and age were predictive indicators of OS. Moreover, there was no significance of the proliferation ability among the three EC cell lines (RL95-2, ISK, and KLE). To reveal the biological roles of miR-940, we respectively transfected RL95-2 cells with miR-940 mimics, miR-940 inhibitors, and control to further investigate the cell proliferation ability, and migration as well as invasion potential of RL95-2 cells. The transfection of miR-940 mimics significantly increased the proliferation and migration/invasion ability of RL95-2 cells. MRVI1 was predicted to be a potential target of miR-940 by means of in silico analysis followed by validation using luciferase reporter assays. MRVI1 was correlated with good prognosis. Moreover, forced expression of MRVI1 in miR-940 mimic transfected cells abolished the facilitation of miR-940 on cell proliferation, migration, and invasion of RL95-2 and KLE cells. In conclusion, our study demonstrates that miR-940 might function as a reliable diagnostic and prognostic signature in EC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31033497

RESUMO

AIMS: Developments in genomic pathology have led to novel molecular classification schemes in gastric cancers. Two of these new subtypes, Epstein-Barr virus (EBV)-associated and microsatellite instability-high (MSI-H), are associated with a dominant T-cell-mediated immune response. The roles of the immune modulators, indoleamine 2, 3-dioxygenase 1 (IDO1) and tryptophanyl-tRNA synthetase (WARS), have not been investigated in the context of this classification. METHODS AND RESULTS: Using in situ hybridization and immunohistochemistry we subclassified 421 primary gastric adenocarcinomas into 5 subtypes, EBV-associated, epithelial to mesenchymal transition, MSI-H, p53-aberrant, and p53-wildtype tumors. Tumor-infiltrative lymphocytes were counted and protein expression of IDO1 and WARS was graded on tissue microarrays of these 421 tumors. High tumor-infiltrative lymphocytes as well as high expression of both IDO1 and WARS was found in EBV and MSI-H tumors. The prognostic effects of IDO1 and WARS expression were tumor subtype dependent. Although high expression levels of IDO1 and WARS were associated with poor prognosis in p53-aberrant, p53-wildtype, and all cancers combined, WARS expression was associated with better prognosis in MSI tumors. CONCLUSIONS: The immunomodulators, IDO1 and WARs, are upregulated and have prognostic significance in EBV-associated and MSI-H tumors. Novel therapies targeting these proteins should be considered in the treatment of these patients.

18.
Theranostics ; 9(5): 1247-1263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30867828

RESUMO

Background and Aims: Prostate specific membrane antigen (PSMA) is specifically expressed on prostate epithelial cells and markedly overexpressed in almost all prostate cancers. TRIM24 is also up-regulated from localized prostate cancer to metastatic castration-resistant prostate cancer (CRPC). Because of the high relevance of TRIM24 for cancer development and the universal expression of PSMA in CPRC, we investigated the efficacy of human monoclonal PSMA antibody (PSMAb)-based platform for the targeted TRIM24 siRNA delivery and its therapeutic efficacy in CRPC in vivo and in vitro. Methods: The therapeutic complexes were constructed by conjugating PSMAb and sulfo-SMCC-protamine, and encapsulating TRIM24 siRNA. Flow cytometry, immunofluorescence, and fluorescence imaging were performed to detect the receptor-binding, internalization, and targeted delivery of PSMAb-sulfo-SMCC-protamine (PSP)-FAM-siRNA complex (PSPS) in vitro and in vivo. CCK-8, plate-colony formation, apoptosis, cell cycle, and Transwell assays were performed to evaluate the therapeutic potential of the PSP-TRIM24 siRNA complex in vitro, whereas the in vivo therapeutic efficacy was monitored by small animal imaging, radiography, and micro CT. Results: We confirmed that PSP could efficiently protect siRNA from enzymatic digestion, enable targeted delivery of siRNA, and internalize and release siRNA into PSMA-positive (PSMA+) prostate cancer cells in vitro and in vivo. Silencing TRIM24 expression by the PSP-TRIM24 siRNA complex could dramatically suppress proliferation, colony-formation, and invasion of PSMA+ CRPC cells in vitro, and inhibit tumor growth of PSMA+ CRPC xenografts and bone loss in PSMA+ CRPC bone metastasis model without obvious toxicity at therapeutic doses in vivo. Conclusion: PSMAb mediated TRIM24 siRNA delivery platform could significantly inhibit cell proliferation, colony-formation, and invasion in PSMA+ CRPC in vitro and suppressed tumor growth and bone loss in PSMA+ CRPC xenograft and bone metastasis model.

19.
Psychooncology ; 28(5): 1142-1148, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30903676

RESUMO

OBJECTIVE: Recent research has documented the harmful effects of ambivalence over emotional expression (AEE) on psychological well-being, but few studies to date have examined AEE among Mainland Chinese breast cancer patients, an ethnic group that prioritizes emotion restraint to preserve social harmony. The present study examined the relationship between AEE and well-being (viz, anxious and depressive symptoms and quality of life) and evaluated perceived social support as a potential mediator of this relationship in a sample of Mainland Chinese breast cancer patients. METHODS: Three hundred twenty-seven Chinese breast cancer patients recruited from Weifang, China, completed a self-reported questionnaire containing the Ambivalence over Emotional Expression Questionnaire (AEQ), the Medical Outcomes Study Social Support Scale (MOS-SSS), the Self-rating Anxiety Scale (SAS), the Self-rating Depression Scale (SDS), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). RESULTS: Overall, Mainland Chinese breast cancer patients endorsed high levels of AEE. A series of mediation analyses revealed perceived social support served as a partial mediator of the relationship between AEE and well-being. Specifically, AEE was associated with lower perceived social support (ßs = -.13, P < .001), which in turn, was associated with greater anxious symptoms (ß = .23, P < .001), depressive symptoms (ß = .20, P < .001) and lower quality of life (ß = -.30, P < .001). CONCLUSIONS: The harmful relationship between AEE and well-being is partially explained by reduced social support. Psychosocial interventions that facilitate emotional disclosure without harming social harmony may be culturally effective for mainland Chinese breast cancer patients.

20.
Nanoscale ; 11(12): 5526-5534, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30860530

RESUMO

The development of facilely synthetic materials for highly efficient enrichment of N-linked glycopeptides is essential in glycoproteome analysis. In this work, by utilizing the self-assembling of glutathione (GSH) on silver nanoparticles (Ag NPs), and the formation and dispersion of Ag NPs on a robust TpPa-1 substrate, a newly functionalized covalent organic framework (COF) called TpPa-1@Ag@GSH was synthesized via a simple two step post-synthetic modification. TpPa-1@Ag@GSH and intermediate products were confirmed and evaluated by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy-energy dispersive spectroscopy, Brunauer-Emmett-Teller and thermogravimetric analyses. Benefiting from the judicious selection of the substrate, the abundance of binding sites, relatively high affinity between GSH and N-linked glycopeptides, and the multivalent interactions between N-linked glycopeptides and unoccupied surfaces of Ag NPs, this porous material showed great performance in N-linked glycopeptide enrichment. By enriching N-linked glycopeptides in tryptic digests of human serum immunoglobulin G (human IgG) followed by mass spectrometry analysis, our method was proved to have good sensitivity (1 fmol), high selectivity (1 : 1500, human IgG to bovine serum albumin), high binding capacity (160 mg g-1, IgG/TpPa-1@Ag@GSH), ultra-fast capture ability (only 1 min incubation time), and good reusability (at least 5 times). It was also successfully applied to the enrichment of N-linked glycopeptides from complex biological samples. Our work improved the enrichment selectivity of COFs, reached the most rapid capture ability among off-column enrichment materials, and provided a very facile and easily popularized post-synthetic modification route for COFs in glycoproteome analysis.


Assuntos
Glutationa/química , Glicopeptídeos/química , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Prata/química , Cromatografia Líquida de Alta Pressão , Glicopeptídeos/análise , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G/metabolismo , Microscopia Eletrônica de Transmissão , Porosidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de Fourier
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA