RESUMO
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. METHODS: To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. RESULTS: After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. CONCLUSIONS: This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.
Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-1alfa/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , China/epidemiologia , Mapeamento Cromossômico , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Padrões de Herança , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de ChancesRESUMO
The incidence and mortality of hepatocellular carcinoma (HCC) is high, but the mechanisms underlying the growth and progression of HCC have not been elucidated. Recently, the ZIC family member 5 (ZIC5) is emerging as an oncogene in various types of tumors. However, its expression and biological role in HCC have not been reported. This study first demonstrated that ZIC5 was up-regulated in HCC specimens, and high ZIC5 expression indicated poor prognosis of HCC patients. In addition, over-expressed ZIC5 promoted the proliferation, migration and invasion of HCC cell lines Huh7 and HepG2 in vitro and in vivo, while ZIC5 knockdown achieved the opposite effects. Actually, ZIC5 increased the expression of genes participating in Wnt/ß-catenin pathway such as ß-catenin and CyclinD1. ZIC5 also promoted ß-catenin to enter the nucleus of HCC cells. Furthermore, silencing ß-catenin abated the promoting role of ZIC5 in HCC. Overall, this study reveals a novel mechanism of ZIC5/ß-catenin that mediates the invasion and metastasis of HCC and ZIC5 serves as a novel indicator for prognosis of HCC patients.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws. METHODS AND RESULTS: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through in vivo and in vitro experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of ß-catenin and its downstream products. CONCLUSIONS: These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.
RESUMO
Objective:To investigate the clinical effect of lateral cervical approach in the treatment of cervical lymphatic tuberculosis complicated with parapharyngeal space abscess. Methods:A total of 10 patients with cervical lymph node tuberculosis complicated with tuberculous abscess in parapharyngeal space were treated. Surgery was performed using a transcervical approach. The operation time and blood loss were recorded. The level of ESR, C-reactive proteinï¼CRPï¼, VAS score and the rating of Kubota drinking test before and 2 weeks after operation were compared. The incision healing, symptoms of tuberculosis poisoning, and the CT findings of the cervical lesions were compared before operation, 2 weeks after operation and at the last follow-up. Results:The operation time ranged from 65 to 130 min with an average of ï¼99.00±21.45ï¼ min. The intraoperative blood loss ranged from 100 to 250 mL with an average of ï¼155.00±43.78ï¼ mL. The average pre-and post-operative level of ESR was ï¼67.60±21.94ï¼ mm/1h and ï¼30.30±13.76ï¼ mm/1h, respectivelyï¼U=5.500, P<0.01ï¼; The average pre-and post-operative level of CRP was ï¼69.70±31.13ï¼ mg/L and ï¼42.40±19.70ï¼ mg/L, respectivelyï¼U=22.500, P<0.05ï¼; The average pre-and post-operative VAS score was ï¼5.60±1.26ï¼ points and ï¼2.50±1.27ï¼ points, respectivelyï¼U=4.500, P<0.01ï¼. As for Kubota drinking test, the rating was between 1-2 two weeks postoperatively. After relieving the compression, there was no obvious choking and coughing in drinking water. During the follow-up period ï¼range: 6-24 monthsï¼, the surgical wound healed completely, and the symptoms of systemic tuberculosis poisoning disappeared. No obvious residual cavity or effusion was found in the parapharyngeal space by CT examination, nor was any protruding tissue in oropharynx. The edema of soft tissue surrounding the operational area disappeared, and the enlarged lymph nodes were significantly reduced. No sign of liquefaction, necrosis, suppuration or recurrence was observed. Conclusion:Surgery using transcervical approach effective in treating cervical lymph node tuberculosis with parapharyngeal space abscess.
Assuntos
Doenças Faríngeas , Tuberculose dos Linfonodos , Abscesso , Humanos , Pescoço , Espaço Parafaríngeo , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose dos Linfonodos/complicaçõesRESUMO
miR-34, whose mimic was used on phase I clinical trial, has been extensively reported since its dysfunction in various cancers including non-small-cell lung cancer (NSCLC). However, the roles of miR-34 family members in the progression of lung squamous carcinoma (SCC) in patients who have occupational-exposure experience are unclear yet. Here, we comprehensively investigated the expression levels of miR-34 family members in SCC patients and compared the roles of them in SCC in vitro and vivo. The results showed that the average levels of miR-34a and miR-34b/c were decreased in patients. The analysis of miR-34a to miR-34b/c levels in patients graded different stages or metastases or recurrence showed that miR-34b/c was reduced earlier and more significantly than miR-34a. In vitro assays demonstrated that both miR-34a and miR-34b/c inhibits SCC cells proliferation, migration and invasion via Notch1 pathway, while miR-34b/c effects more than miR-34a does. As miR-34a was significantly decreased in cancer recurrence, the further analysis of relationship between miR-34a and stem cell adhesion molecular CD44 showed that miR-34a was significantly correlated with CD44 levels in patients. Knockdown of CD44 significantly blocked miR-34a mediated inhibition of cell migration and invasion. Treating the purified CD44hi cells with miR-34 overexpression lentivirus inhibited the tumor outgrowth. By contrast, anti-miR-34 facilitated tumor development of CD44low cells. Our study showed that miR-34 family members are negative regulator for SCC development, even though the inhibition is mediated by multiple and complicated signal pathways, which provides theoretical basis for SCC treatment and a biomarker candidate for SCC prognosis.