MicroRNA-543 (miR-543) has been suggested as an important regulator of the development and progression of various cancer types. However, the role and biological function of miR-543 in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we found that miR-543 expression was significantly increased in tumor tissues from ccRCC patients and ccRCC cell lines. We found that overexpression of miR-543 markedly promoted the proliferation and invasion of ccRCC cells, whereas suppression of miR-543 had the opposite effects. Krüppel-like factor 6 (KLF6) was identified as a target gene of miR-543. Furthermore, we found that miR-543 negatively regulates the expression of KLF6 and p21 in ccRCC cells. Overexpression of KLF6 markedly attenuated the oncogenic effect of miR-543 overexpression. Moreover, knockdown of KLF6 significantly reversed the antitumor effect of miR-543 inhibition. Overall, our results demonstrate that miR-543 promotes the proliferation and invasion of ccRCC cells by targeting KLF6 and suggest that miR-543 may serve as a potential therapeutic target for treatment of ccRCC.
Radiosensitivity of prostate cancer (PCa) cells promotes the curative treatment for PCa. The present study was designed to investigate the synergistic effect of genistein and AG1024 on the radiosensitivity of PCa cells. The optimal X‑irradiation dose (4 Gy) and genistein concentration (30 µM) were selected by using the CCK‑8 assay. Before X‑irradiation (4 Gy), PC3 and DU145 cells were treated with genistein (30 µM), AG1024 (10 µM) and their combination. All treatments significantly reduced cell proliferation and enhanced cell apoptosis. Using flow cytometric analysis, we found that genistein arrested the cell cycle at S phase and AG1024 arrested the cell cycle at G2/M phase. Genistein treatment suppressed the homologous recombination (HRR) and the non‑homologous end joining (NHEJ) pathways by inhibiting the expression of Rad51 and Ku70, and AG1024 treatment only inhibited the NHEJ pathway via the inactivation of Ku70 as detected by western blot analysis. Moreover, the combination treatment with genistein and AG1024 more effectively radiosensitized PCa cells than single treatments by suppressing cell proliferation, enhancing cell apoptosis and inactivating the HRR and NHEJ pathways. In vivo experiments demonstrated that animals receiving the combination treatment with genistein and AG1024 displayed obviously decreased tumor volume compared with animals treated with single treatment with either genistein or AG1024. We conclude that the combination of genistein (30 µM) and AG1024 (10 µM) exhibited a synergistic effect on the radiosensitivity of PCa cells by suppressing the HRR and NHEJ pathways.
Rapid urbanization presents significant challenges to biodiversity through habitat degradation, fragmentation, and loss. This study focuses on Shenzhen, China, a highly urbanized region experiencing substantial land use changes and facing a considerable risk of biodiversity decline, to investigate the dynamics of habitat quality over two critical periods: 2010–2015 and 2015–2020. Using the InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) model for habitat quality assessment and Bayesian networks to analyze causal relationships, this research offers an innovative comparison between habitat recovery and degradation across these two phases. Results indicate that from 2010 to 2015, localized habitat recovery was achieved on 0.53% of the land area due to restoration policies, yet the overall trend remained negative. During the 2015–2020 period, habitat degradation intensified (7.19%) compared to recovery (5.7%); notably, 70.6% of areas that had been previously restored are now experiencing degradation once again. This re-degradation highlights the instability of earlier restoration efforts under ongoing urban pressure. By integrating spatial analysis with Bayesian network modeling, this study provides offers a nuanced understanding of where and why initial recovery efforts were unsuccessful, identifying areas susceptible to persistent degradation. The research emphasizes that urban expansion—particularly the development of construction land, was the primary driver of habitat degradation, while ecological sensitivity played a crucial role in determining the long-term success of recovery efforts. This approach provides valuable insights for designing more effective, sustainable conservation strategies in rapidly urbanizing regions.
Abstract Background Recently, the anti-tumor activity of N-myc downstream-regulated gene 2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma (CCRCC), but the role of the down-expression of NDRG2 has not been described. Methods The NDRG2 recombinant adenovirus plasmid was constructed. The proliferation rate and NDRG2 expression of cell infected with recombinant plasmid were mesured by MTT, Flow cytometry analysis and western blot. Results The CCRCC cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and significantly decreased the proliferation rate. Fluorescence activated cell sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were in G1-phase compared to 54.39% of control cells ( P < 0.05). In addition, there were much more apoptotic cells in NDRG2-expressing cells than in the controls ( P < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected examined by western blot. Furthermore, we found that p53 could upregulate NDRG2 expression in A-498 cell. Conclusions We found that NDRG2 can inhibit the proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can up-regulate the expression of NDRG2. Our results showed that NDRG2 may function as a tumor suppressor in CCRCC.
Abstract Background NDRG 2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG 2 expressed differentially in normal and cancer tissues. Specifically, NDRG 2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG 2 inhibited the proliferation of cancer cells. NDRG 2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG 2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG 2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG 2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG 2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG 2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG 2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.
Histone deacetylases (HDACs) are overexpressed in various cancers. In vivo imaging to measure the expression and functions of HDACs in tumor plays an important role for tumor diagnosis and HDAC-targeted therapy evaluation. The development of stable and highly sensitive HDAC targeting probe is highly desirable. Near-infrared (NIR) fluorescence optical imaging is a powerful technology for visualizing disease at the molecular level in vivo with high sensitivity and no ionizing radiation. We report here the design, synthesis, and bioactivity evaluation of LBH589–Cy5.5 for in vivo NIR fluorescence imaging of HDACs. The IC50 value of the resulting NIR probe to HDACs was determined to be 9.6 nM. In vitro fluorescence microscopic studies using a triple-negative breast cancer cell line, MDA-MB-231, established the binding specificity of LBH589–Cy5.5 to HDACs. An in vivo imaging study performed in MDA-MB-231 tumor xenografts demonstrated accumulation of the probe in tumor with good contrast from 2 h to 48 h postinjection. Furthermore, the fluorescent signal of LBH589–Cy5.5 in tumor was successfully blocked by coinjection of nonfluorescent LBH589 with the probe. In a following therapy evaluation study, the administration of SAHA, a clinically used HDAC inhibitor, decreased LBH589–Cy5.5 accumulation in tumor, demonstrating the potential application of LBH589–Cy5.5 for evaluating therapeutic response of HDAC inhibitors in cancer treatment.
morbidity, mortality and cost (1, 3,21), posing a major threat to the well-being of post-surgical patients.Although complete eradication of SSIs seems impossible to achieve, most of them are potentially preventable though effective prevention strategies (7).Scrupulous surveillance, as growing studies indicated (5), can lead to a substantial reduction in the incidence of SSIs.Haley et al. ( 9) reported that hospitals with a robust surveillance and control program were able to lower their SSI rates by 19-41% over the course of 6 years.Based on data from Dutch surveillance system, █ INTRODUCTION Surgical site infections (SSIs) are the most commonly encountered healthcare-associated infections among surgically treated patients (18).The reported incidence of SSIs varies widely, ranging from 1% to 17%, depending on the definitions used for infection, length of postoperative follow-up, reporting institution, and the type of surgical procedure (13,15,29,30).Despite the marked improvement in surgical practice and infection control techniques, SSIs remain a worrisome burden of hazard for both patients and healthcare services in terms of AIM: To estimate the effect of a multimodal prevention program on controlling surgical site infection (SSI) risk among neurosurgical patients. MATERIAl and METhODS:This prospective study was conducted among adult patients who have undergone neurosurgical procedures in a tertiary-care university-affiliated hospital during January 2008 to December 2013 since the implementation of an infection control program.SSI cases among inpatients were identified by daily active searches, whereas post-discharge surveillance was performed for outpatients through telephone contact 30-35 days after surgery, according to the definition proposed by the Center for Disease Control.The variation of SSI rate during the study period was analyzed by Cochran-Armitage trend test.RESUlTS: Overall, a total of 3042 patients were enrolled and 112 SSI cases were identified during the studied period.SSI more likely occurred in patients with older age (t=5.16,p<0.01), undergoing emergency operations (x 2 =50.5, p<0.01), having higher American Society of Anesthesiologists (ASA) scores (x 2 =7.2, p=0.01) and clean contaminated wound or above (x 2 =53.8, p<0.01).The annual incidence rate of SSI was 6.21%, 5.01%, 3.89%, 3.06%, 2.38% and 2.28%, respectively, showing a significant decreasing trend (z=3.96,p<0.01). CONClUSION:The results provide evidence of a significant decreasing trend in the SSI rate following the infection prevention program, demonstrating the role of multimodal approach in controlling SSI.
Abstract The tumor suppressive role of MIR22HG has been studied in several types of cancer. We analyzed the TCGA dataset and found the down-regulation of MIR22HG in bladder cancer (BC). Bioinformatics analysis predicted the interaction between MIR22HG and miR-486. The direct interaction between MIR22HG and miR-486 was also confirmed by dual luciferase assay. However, overexpression of these two factors did not significantly affect the expression of each other. Interestingly, overexpression of MIR22HG led to up-regulated phosphatase and tensin homolog (PTEN), which is a target of miR-486. In cell proliferation assay, overexpression of MIR22HG and PTEN led to decreased rates of BC cell proliferation. Moreover, overexpression of miR-486 played an opposite role and attenuated the effects of overexpression of MIR22HG and PTEN. Therefore, MIR22HG regulates miR-486/PTEN axis to promote cell proliferation in BC.
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