ABSTRACT
Pillararenes have gained great interest among researchers in many fields due to their symmetric structure and facile functionalization. In this review, we summarize recent progress for pillararenes as antimicrobial agents, ranging from cationic pillararenes and peptide-modified pillararenes to sugar-functionalized pillararenes. Moreover, their structure-activity relationships are presented, and their mechanisms of action are discussed. As a state-of-the-art technology, their opportunities and outlook are also outlined in this emerging field. Overall, their potent inhibitory activity and high biocompatibility give them potential for the development of novel antimicrobial agents.
Subject(s)
Anti-Infective Agents , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Humans , Structure-Activity Relationship , Microbial Sensitivity Tests , Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Molecular StructureABSTRACT
OBJECTIVE: To compare natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic (LAP) surgery in treating colorectal cancer. METHODS: The present authors conducted a systematic search in the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), prospective nonrandomized studies, and retrospective studies up to May 2019. We used postoperative complications as the main endpoints, and used hospital stay, time to first flatus, operative time, postoperative pain, cosmetic result, wound infections, and oncological outcomes as the secondary endpoints. Subgroup analyses were conducted according to the different specimen extraction sites (transanal and transvaginal). A sensitivity analysis was carried out to evaluate the reliability of the outcomes. RevMan5.3 software was used for statistical analysis. RESULT: Twelve studies (one RCT, ten retrospective studies, and one prospective nonrandomized study) involving a total of 1437 patients (NOSES group 665 patients and LAP surgery group 772 patients) were included. Meta-analysis showed that compared with LAP surgery, NOSES resulted in a shorter hospital stay (WMD = -0.79 days; 95% CI -1.17 to -0.42; P < 0.001; P = 0.02), a shorter time to first flatus (WMD = -0.58 days; 95% CI -0.75 to -0.40; P < 0.001), less postoperative pain (WMD = -1.51; 95% CI -1.99 to -1.04; P < 0.001), a better cosmetic result (WMD = 1.37; 95% CI 0.59 to 2.14; P < 0.001), and fewer wound infections (OR = 0.13; 95% CI 0.05 to 0.35; P < 0.001) and postoperative complications (OR = 0.48; 95% CI 0.36 to 0.65; P < 0.001). Oncological outcomes did not differ between the two groups, while the operative time (WMD = 13.95 min; 95% CI 4.55 to 23.35; P = 0.004) was longer in the NOSES group. CONCLUSION: The present systematic meta-analysis is an attempt to assess the impact of NOSES, namely, its oncological outcomes and surgical safety in colorectal cancer patients. Pooled comparisons revealed that NOSES was superior to LAP surgery in terms of postoperative morbidity, postoperative pain, hospital stay, the time to first flatus, cosmetic results, and wound infections; however, NOSES was associated with a longer operative time. Considering the abovementioned limitations and the very low level of evidence of the comparisons, further RCTs are required to verify the results of our study.
Subject(s)
Colorectal Neoplasms , Laparoscopy , Colorectal Neoplasms/surgery , Humans , Length of Stay , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment OutcomeABSTRACT
The purpose of this study was to investigate the expression of microRNA-202 (miR-202) and its role in colorectal cancer (CRC) in vivo and in vitro. We examined the expression of miR-202 in CRC tissues by quantitative real-time PCR (qRT-PCR) assay. Lentiviral vectors were constructed to overexpress or inhibit the expression of miR-202 in the CRC cell lines HCT116 and SW480 to determine its effects on cell invasion and proliferation. We found that overexpression of miR-202 significantly inhibited the proliferation and invasion of HCT116 cells. MiRNA target gene prediction, dual luciferase assay, and western blot analysis demonstrated that miR-202 regulated ubiquitin-like with PHD and RING finger domain 1 (UHRF1) expression in both cell lines. The effect of miR-202 on cell proliferation and invasion was partially reversed by activating the expression of UHRF1. Furthermore, miR-202 induced tumor formation in HCT116 xenograft BALB/c nude mice. Mice vaccinated with miR-202-overexpressing cells had smaller tumors and lower UHRF1 expression than the control group. These results indicate the possibility that miR-202 is under-expressed in CRC tissues, and that miR-202 inhibits the proliferation and invasion of CRC via targeting UHRF1. MiR-202 is a potential therapeutic target for CRC.
Subject(s)
CCAAT-Enhancer-Binding Proteins/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Animals , Cell Line, Tumor , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , HCT116 Cells , HEK293 Cells , HT29 Cells , Humans , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Transplantation, Heterologous , Tumor Burden/genetics , Ubiquitin-Protein LigasesABSTRACT
The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes.
Subject(s)
Antiviral Agents/pharmacology , Cyclopentanes/pharmacology , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Influenza A Virus, H7N9 Subtype/drug effects , Orthomyxoviridae Infections/drug therapy , Acids, Carbocyclic , Animals , Dogs , Drug Administration Schedule , Female , Humans , Influenza A Virus, H7N9 Subtype/enzymology , Influenza A Virus, H7N9 Subtype/growth & development , Injections, Intramuscular , Lung/drug effects , Lung/pathology , Lung/virology , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred C57BL , Neuraminidase/antagonists & inhibitors , Neuraminidase/metabolism , Orthomyxoviridae Infections/mortality , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Oseltamivir/pharmacology , Survival Analysis , Treatment Outcome , Viral Load/drug effects , Viral Proteins/antagonists & inhibitors , Viral Proteins/metabolism , Virus Replication/drug effectsABSTRACT
BACKGROUND: Influenza H7N9 has become an endemic pathogen in China where circulating virus is found extensively in wild birds and domestic poultry. Two epidemic waves of Human H7N9 infections have taken place in Eastern and South Central China during the years of 2013 and 2014. In this study, we report on the first four human cases of influenza H7N9 in Shantou, Guangdong province, which occurred during the second H7N9 wave, and the subsequent analysis of the viral isolates. METHODS: Viral genomes were subjected to multisegment amplification and sequenced in an Illumina MiSeq. Later, phylogenetic analyses of influenza H7N9 viruses were performed to establish the evolutionary context of the disease in humans. RESULTS: The sequences of the isolates from Shantou have closer evolutionary proximity to the predominant Eastern H7N9 cluster (similar to A/Shanghai/1/2013 (H7N9)) than to the Southern H7N9 cluster (similar to A/Guangdong/1/2013 (H7N9)). CONCLUSIONS: Two distinct phylogenetic groups of influenza H7N9 circulate currently in China and cause infections in humans as a consequence of cross-species spillover from the avian disease. The Eastern cluster, which includes the four isolates from Shantou, presents a wide geographic distribution and overlaps with the more restricted area of circulation of the Southern cluster. Continued monitoring of the avian disease is of critical importance to better understand and predict the epidemiological behaviour of the human cases.
Subject(s)
Genome, Viral/genetics , Influenza A Virus, H7N9 Subtype/genetics , Influenza, Human/epidemiology , RNA, Viral/analysis , China/epidemiology , Genetic Variation , Humans , Influenza A Virus, H7N9 Subtype/isolation & purification , Influenza, Human/virology , PhylogenySubject(s)
Infectious Disease Transmission, Patient-to-Professional , Influenza A Virus, H7N9 Subtype/genetics , Influenza, Human/transmission , Adult , China , Cross Infection , Hospitals, University , Humans , Influenza A Virus, H7N9 Subtype/isolation & purification , Influenza, Human/virology , Male , Phylogeny , Real-Time Polymerase Chain ReactionABSTRACT
Deciphering cellular interactions is essential to both understand the mechanisms underlying a broad range of human diseases, but also to manipulate therapies targeting these diseases. Here, the formation of cell doublets resulting from specific membrane ligand-receptor interactions is discovered. Based on this phenomenon, the study developed DoubletSeeker, a novel high-throughput method for the reliable identification of ligand-receptor interactions. The study shows that DoubletSeeker can accurately identify T cell receptor (TCR)-antigen interactions with high sensitivity and specificity. Notably, DoubletSeeker effectively captured paired TCR-peptide major histocompatibility complex (pMHC) information during a highly complex library-on-library screening and successfully identified three mutant TCRs that specifically recognize the MART-1 epitope. In turn, DoubletSeeker can act as an antigen discovery platform that allows for the development of novel immunotherapy targets, making it valuable for investigating fundamental tumor immunology.
Subject(s)
Antigens , Receptors, Antigen, T-Cell , Humans , Ligands , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Peptides , Major Histocompatibility ComplexABSTRACT
BACKGROUND: The KiSS1 gene is considered a tumor suppressor in various cancers. MicroRNAs are involved in many important life processes, and their regulation of gene expression may be as important as that of transcription factors. Here, we explore the roles of miR-124-3p and miR-378-3p in colorectal cancer and their relationships with the KiSS1 gene. METHODS: The effects of miR-124-3p and miR-378-3p on KiSS1 protein expression were observed by transfecting colorectal cancer cells (SW-480) with miR-124-3p and miR-378-3p mimics and inhibitors. Moreover, cell proliferation, migration and invasion were evaluated by ethynyl-20-deoxyuridine and Transwell experiments. RESULTS: The KiSS1 mRNA and protein expression levels were significantly increased in mimic-transfected cells compared with those in untransfected cells, and the proliferation, migration and invasion abilities of the former were decreased; in addition, opposing results were obtained in the inhibitor and mimic groups. CONCLUSIONS: In conclusion, our studies indicate that miR-124-3p and miR-378-3p upregulate the expression of KiSS1 and are associated with colorectal cancer metastasis and progression. miR-124-3p, miR-378-3p and KiSS1 may play important roles in colorectal cancer.
ABSTRACT
BACKGROUND: The UHRF1 gene is an epigenetic modification factor that mediates tumor suppressor gene silencing in a variety of cancers. Related studies have reported that UHRF1 can inhibit the expression of the KISS1 gene. However, the regulatory mechanism underlying UHRF1 expression in colorectal cancer (CRC) is still unclear. The aim of this study was to gain a better understanding of the regulation of UHRF1 expression in CRC and to determine whether it regulates the mechanism by which KISS1 promotes CRC metastasis. METHODS: In the present study, the levels of miR-506, UHRF1 and KISS1 expression in CRC tissues and in human CRC cell lines were studied using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation, migration, and invasion assays are used to detect cell proliferation, migration, and invasion. A dual-luciferase reporter system was used to confirm the target gene of miR-506. RESULTS: This study found that UHRF1 protein is highly expressed in CRC tissues and negatively correlated with KISS1 protein expression. UHRF1 overexpression activates the PI3K/NF-κB signaling pathway by inhibiting the mRNA expression levels of pathway mediators. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-506 targets UHRF1. CONCLUSION: This study identified the regulation of UHRF1 expression in CRC and the mechanism of CRC metastasis. UHRF1 may be a new potential target molecule for future CRC metastasis treatment.
ABSTRACT
Colorectal cancer (CRC) is one of the most common cancers of the digestive tract. Although numerous studies have been conducted to elucidate the cause of CRC, the exact mechanism of CRC development remains to be determined. To identify candidate genes that may be involved in CRC development and progression, the microarray datasets GSE41657, GSE77953 and GSE113513 were downloaded from the Gene Expression Omnibus database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional enrichment analysis of differentially expressed genes (DEGs). A protein-protein interaction network was constructed, and the hub genes were subjected to module analysis and identification using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 142 DEGs were identified, with enriched functions and pathways in the 'cell cycle', 'cell proliferation', 'the mitotic cell cycle' and 'one-carbon metabolic process'. In addition, 10 hub genes were identified, and functional analysis indicated that these genes are mainly enriched in 'cell division', 'cell cycle' and functions associated with nucleotide binding processes. Survival analysis demonstrated that DNA topoisomerase II α, cyclin-dependent kinase 1 and CDC28 protein kinase regulatory subunit 2 may be involved in cancer invasion or recurrence. The DEGs identified in the present study may help explain the molecular mechanisms of CRC development and progression.
ABSTRACT
Analysis of gene expression data by clustering and visualizing played a central role in obtaining biological knowledge. Here, we used Pearson's correlation coefficient of multiple-cumulative probabilities (PCC-MCP) of genes to define the similarity of gene expression behaviors. To answer the challenge of the high-dimensional MCPs, we used icc-cluster, a clustering algorithm that obtained solutions by iterating clustering centers, with PCC-MCP to group genes. We then used t-statistic stochastic neighbor embedding (t-SNE) of KC-data to generate optimal maps for clusters of MCP (t-SNE-MCP-O maps). From the analysis of several transcriptome data sets, we demonstrated clear advantages for using icc-cluster with PCC-MCP over commonly used clustering methods. t-SNE-MCP-O was also shown to give clearly projecting boundaries for clusters of PCC-MCP, which made the relationships between clusters easy to visualize and understand.
ABSTRACT
Southern China experienced few cases of H7N9 during the first wave of human infections in the spring of 2013. The second and now the third waves of H7N9 infections have been localized mostly in Southern China with the Guangdong province an epicenter for the generation of novel H7N9 reassortants. Clusters of human infections show human-to-human transmission to be a rare but well-documented event. A recent cluster of infections involving hospital health care workers stresses the importance of care givers utilizing personal protective equipment in treating H7N9 infected or suspected patients.