Integrated bioinformatics analysis of microarray data from non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), with its high mortality rate, lack of early diagnostic markers and prevention of distant metastases are the main challenges in treatment. To identify potential miRNAs and key genes in NSCLC to find new biomarkers and target gene therapies. The GSE102286, GSE56036, GSE25508, GSE53882, GSE29248 and GSE101929 datasets were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially co-expressed miRNAs (DE-miRNAs) and lncRNAs (DElncRs) by GEO2R and R software package. Pathway enrichment analysis of DE-miRNAs-target genes was performed by String and Funrich database to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) network and visualized with Cytoscape software. Nineteen co-expressed DE-miRNAs were screened from five datasets. The 7683 predicted up- and down-regulated DE-miRNAs-target genes were significantly concentrated in cancer-related pathways. The top 10 hub nodes in the PPI were identified as hub genes, such as MYC, EGFR, HSP90AA1 and TP53, MYC, and ACTB. By constructing miRNA-hub gene networks, hsa-miR-21, hsa-miR-141, hsa-miR-200b and hsa-miR-30a, hsa-miR-30d, hsa-miR-145 may regulate most hub genes and hsa-miR-141, hsa-miR-200, hsa-miR-145 had higher levels in the miRNA and ceRNA regulatory networks, respectively. In conclusion, the identification of hsa-miR-21, hsa-miR-141, hsa-miR-200b hsa-miR-30a, hsa-miR-30d and hsa-miR-145 provides a new theoretical basis for understanding the development of NSCLC.

Integrated Network Analysis to Determine CNN1, MYL9, TAGLN, and SORBS1 as Potential Key Genes Associated with Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is challenging to treat. It is necessary to screen for related biological markers to accurately predict the prognosis and recurrence of prostate cancer. METHODS: Three data sets, GSE28204, GSE30521, and GSE69223, from the Gene Expression Omnibus (GEO) database were integrated into this study. After the identification of differentially expressed genes (DEGs) between PCa and normal prostate tissues, network analyses including protein-protein interaction (PPI) network, and weighted gene co-expression network analysis (WGCNA) were used to select hub genes. Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to annotate the functions of DEGs and hub modules of the networks. Survival analysis was performed to validate the correlation between the key genes and PCa relapse. RESULTS: In total, 867 DEGs were identified, including 201 upregulated and 666 downregulated genes. Three hub modules of the PPI network and one hub module of the weighted gene co-expression network were determined. Moreover, four key genes (CNN1, MYL9, TAGLN, and SORBS1) were significantly associated with PCa relapse (p < 0.05). CONCLUSIONS: CNN1, MYL9, TAGLN, and SORBS1 may be potential biomarkers for PCa development.

Risk Correlation Analysis between Polycystic Ovary Syndrome (PCOS) and Serum Visfatin Levels in Middle-Aged Women: Systematic Review and Meta-Analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder that occurs frequently in women of childbearing age and is associated with insulin resistance. Serum visfatin can affect insulin resistance by binding to insulin receptors and further affect the occurrence and development of PCOS. In this study, we investigated the current status of serum visfatin levels in patients with PCOS through a literature search and meta-analysis. METHODS: We searched online Pubmed, Embase, Web of Science, the Cochrane Library, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc) databases and registered websites such as the ICTRP (International Clinical Trial Registration Platform) and clinicaltrials.gov (https://clinicaltrials.gov/) for case-control studies on PCOS and visfatin levels, assessed the quality of the included articles with the Newcastle-Ottawa Scale (NOS scale), and combined the comparison of serum visfatin levels between patients with PCOS and healthy individuals from high-quality studies. RESULTS: 20 research papers were included in the quantitative analysis of this study. The combined analysis showed that obese patients with PCOS had statistically significantly higher visfatin levels than healthy people [MD (mean difference) = 12.94, 95% CI (confidence interval) (6.52-19.37), Z = 3.95, p < 0.0001]. Visfatin levels were higher in non-obese patients with PCOS than in healthy people and are statistically significant [MD = 14.98, 95% CI (5.80-24.16), Z = 3.20, p = 0.001]. Heterogeneity in the combined analysis was not related to study location, the publication year of the literature, source of serum samples, but was influenced by the quality of the literature. After excluding the most influential papers, the combined analysis was conducted again, and the conclusion was consistent with that before the exclusion. The results of Egger's test showed no significant publication bias. CONCLUSIONS: High serum visfatin levels are a natural feature of PCOS and are not associated with obesity; Serum visfatin levels may be a potential marker for the diagnosis of PCOS, but their relationship with PCOS and insulin resistance remains worthy of in-depth investigation.

HSPB8 facilitates prostate cancer progression via activating the JAK/STAT3 signaling pathway.

Prostate cancer (PC) is a clinically and biologically heterogeneous disease that lacks effective treatment. Heat shock protein B8 (HSPB8) is an important factor in the progression of various types of cancer. However, the clinical significance and biological role of HSPB8 in PC are still unclear. In this study, we determined HSPB8 expression in PC tissues by immunohistochemical staining and explored the in vitro functions of HSPB8 using HSPB8 knockdown DU145 and LNcap PC cell lines. The in vivo effect of HSPB8 was explored by a subcutaneous xenograft mice model. The human phospho-kinase array and signal transducer and activator of transcription (STAT) 3 activator were utilized to explore the potential mechanism of HSPB8-induced PC progression. As a result, we found that HSPB8 was abundantly expressed in PC tissues and cell lines. HSPB8 knockdown inhibited cell proliferation and migration, promoted apoptosis and cycle repression, as well as weakened tumorigenesis ability. Mechanistically, we demonstrated that HSPB8 facilitates the malignant phenotypes of PC by activating the Janus kinase/STAT3 signaling pathway. These results proposed that HSPB8 seems to be an attractive therapeutic target for PC patients.

CACYBP knockdown inhibits progression of prostate cancer via p53.

PURPOSE: Prostate cancer (PC) is one of the most common malignant tumors of genitourinary system in men. CACYCLIN binding protein (CACYBP) is involved in the progression of a variety of cancers. The aim of this study was to explore the expression and functional role of CACYBP in PC. METHODS: The expression of CACYBP in PC was evaluated by immunohistochemical (IHC) staining and qRT-PCR. Subsequently, we established lentivirus-mediated CACYBP knockdown in PC cell lines. The biological roles of CACYBP on proliferation, apoptosis, cycle distribution, migration and tumor formation of PC were investigated by Celigo cell counting assay, flow cytometry, transwell assay, wound-healing assay and mice xenograft models, respectively. RESULTS: CACYBP was highly expressed in PC and was positively correlated with the pathological grade of PC patients. Knockdown of CACYBP inhibited proliferation, enhanced apoptosis, arrested cell cycle in G2 and suppressed migration of PC cell lines in vitro. In addition, CACYBP knockdown weakened the tumor growth of PC in vivo. Moreover, addition of p53 inhibitor could effectively alleviate the inhibitory effect of CACYBP knockdown on cell activity. CONCLUSION: This study revealed that knockdown of CACYBP inhibited the proliferation, migration and tumorigenicity of PC, which may serve as a potential therapeutic target for the treatment of PC.

Rationally Designed Oral DOX Gels for Colon-Specific Administration.

Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women. Traditional CRC dosage forms deliver the drug to both desired and unwanted sites of drug action, resulting in a number of negative side effects. Chemotherapeutic and chemopreventive agents are being targeted and delivered directly to the colon and rectum using targeted oral drug delivery systems. The main challenge in successfully targeting drugs to the colon via the oral route is avoiding drug absorption/degradation in the stomach and small intestine before the dosage form reaches the colon. In this study, we employed biocompatible chalk to adsorb DOX, then mixed pectin and cross-linked with calcium ions to form PC-DOX gels. The presence of cross-linked pectin and chalk can provide dual protection for the drug, significantly reducing drug leakage in gastric acid. In vitro release results showed that the designed PC-DOX could achieve 68% colon delivery efficiency. In the simulated colon environment, the released semi-degradable chalk did not affect the uptake of doxorubicin by colon cancer cells. Finally, in vivo simulation experiments in mice showed that rationally designed PC-DOX could achieve the highest colonic delivery efficiency. Our strategy has great potential for application in the treatment of colon cancer.

Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis.

Galectin-3 has an important function in the development of tumors. The purpose of this meta-analysis was to explore the relationships between the expression of galectin-3 on clinicopathological features and prognosis of colorectal cancer (CRC). A comprehensive literature search was used to identify eligible studies, and Stata software was conducted using in this meta-analysis. A total of 15 studies, including 1661 cases, were matched in the inclusion criteria. The pooled analysis indicated that galectin-3 expression was related to the poor overall survival (OS) in CRC patients (HR: 1.77, 95% CI: 1.36-2.31, P < 0.0001). Our meta-analysis also showed that cancerous tissues have higher levels of galectin-3 expression than normal tissues. Besides, positive galectin-3 expression was also related to advanced TNM stages(III/IV vs. I/II: OR 5.30, 95% CI: 2.42-11.61, P < 0.0001), higher Duke's stages (C/D vs. A/B: OR 4.00, 95% CI: 2.22-7.22, P < 0.0001), venous invasion (venous invasion vs. not: OR 3.02, 95%CI: 1.75-5.22, P < 0.0001) and higher CEA level (CEA≥5 ng/ml vs. ≤ 5 ng/ml: OR 2.09, 95% CI: 1.09-4.03, P = 0.03). In summary, our results indicated that overexpression of galectin-3 is significantly related to the tumor progression and could be a efficient in predicting the prognosis of patients with CRC.

Resolving quantum dots and peptide assembly and disassembly using bending capillary electrophoresis.

Despite the numerous techniques developed for the studying nanoparticle and peptide interaction nowadays, sensitive and convenient assay in the process of flow, especially to simulate the self-assembly of quantum dots (QDs) and peptide inflow in blood vessels, still remains big challenges. Here, we report a novel assay for studying the self-assembly of QDs and peptide, based on CE using a bending capillary. We demonstrate that the semicircles numbers of the bending capillary affect the self-assembly kinetics of CdSe/ZnS QDs and ATTO-D3 LVPRGSGP9 G2 H6 peptide. Moreover, benefitting from this novel assay, the effect of the position on the self-assembly has also been realized. More importantly, we also demonstrate that this novel assay can be used for studying the stability of the QDs-peptide complex inflow. We believe that our novel assay proposed in this work could be further used as a general strategy for the studying nanoparticle-biomolecule interaction or biomolecule-biomolecule interaction.

A novel in-capillary assay for dynamically monitoring fast binding between antibody and peptides using CE.

Nowadays, despite numerous techniques available for the detection of antibody-peptide binding, sensitivity and detection limit inflow still remains a major challenge. Herein, we report a strategy for the detection of binding inflow of monoclonal anti-FLAG M2 antibody and 5,6-carboxyfluorescein-labeled FLAG tag in capillary. Antibody and peptides were sequentially injected into the capillary where they mixed and bound together. Capillary electrophoresis with fluorescence detection was employed to monitor the binding process, and the results showed that the efficacy of the antibody-peptide binding in capillary (in-capillary assay) is affected by the stoichiometry. Compared to the out-capillary assay, this novel assay showed different KD values and required a very short detection time, thus showing great potential for rapid detection as well as other applications. Additionally, our novel assay can be used to investigate the stability of the antibody-peptide complex. The addition of excess DYKDDDDK or TAMRA-DYKDDDDK, with similar binding priorities with M2, can leads to dissociation of the complex with a two-step mechanism including dissociation and association. We believed that our developed method can be extended to monitor wide range of other biomolecule interactions.