RESUMEN

Background: Our study analyzed the immune infiltration of esophageal adenocarcinoma (EAC) tumor cells and identified long non-coding ribonucleic acid (lncRNA) genes to construct a prognostic model of EAC to evaluate the survival prognosis of patients and explore potential therapeutic targets. Methods: The data of 89 patients with EAC, including 11 normal tissue samples and 78 EAC of tumor tissue samples, were downloaded from The Cancer Genome Atlas public database. Perl script and R software were used to run the code, conduct the statistical analysis, calculate the risk coefficients of the patients, and conduct the Cox regression analysis, immune-related lncRNA survival analysis, risk analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) curve analysis. Results: We screened and identified 19 prognostic biomarkers, including LINC01612, AC008443.2, and LINC02582, allocated the patients into high- and low-risk groups, and found significant differences in the prognosis between the high- and low-risk groups using the Kaplan-Meier survival analysis (P<0.001). A ROC curve was used to evaluate the feasibility of the prognostic model for EAC, and we found that the model had high predictability (area under the curve =0.964). A PCA analysis was performed of the complex transcriptome sequencing data and other cubes to transform the data into a 3-dimensional space constructed by feature vectors. Conclusions: Our study effectively screened and identified the lncRNA genes related to the immune infiltration of EAC and successfully constructed a prognostic model. In total, 19 potential diagnostic and therapeutic target genes, including LINC01612, AC008443.2, and LINC02582, were identified that have certain significance in guiding the clinical treatment of EAC patients.

RESUMEN

A viable therapy is needed to overcome the deadlock of the incurable chronic hepatitis B (CHB). The prolonged existence of covalently closed circular DNA (cccDNA) and integrated HBV DNA in the nucleus of hepatocytes is the root cause of CHB. As a result, it is critical to successfully suppress HBV DNA replication and eliminate cccDNA. RNA interference has been proven in recent research to silence the expression of target genes and thereby decrease HBV replication. However, siRNA is susceptible to be degraded by RNA enzymes in vivo, making it difficult to deliver successfully and lacking of tissue targeting. To exploit the advantages of siRNA technology while also overcoming its limitations, we designed a new strategy and prepared biomimetic nanoparticles that were directed by PreS/2-21 peptides and precisely loaded HBV siRNA. Experiments on these nanoparticles in vitro and in vivo revealed that they are tiny, stable, safe and highly targetable, with high inhibitory effects on HBV DNA, pgRNA, cccDNA, HBeAg and HBsAg. PreS/2-21-directed nanoparticles loaded with HBV gene therapy drugs are expected to be promising for the treatment of CHB.

Asunto(s)

RESUMEN

This study aims to identify differentially expressed microRNAs (miRNAs) in gastric cancer by comparing gastric cancerous tissues with normal tissues, explore the potential roles.The miRNA expression microarray was employed on gastric cancer tissues, and apparently normal para-cancerous tissues from 3 patients undergoing radical surgery were matched. Quantitative RT-PCR was performed on the other 7 patients to validate the findings of the microarray. Furthermore, Gene Ontology (GO) analysis and enrichment analysis of KEGG Pathway were performed for 5 dysregulated candidate miRNAs, including 3 upregulated (miR-31-3p, miR-6736-3p, and miR-147b) and 2 downregulated (miR-3065-5p and miR-3921) miRNAs, in order to determine the role of miRNAs in tumorigenesis and development.Among these miRNAs, 17 miRNAs were found to be upregulated, and 19 miRNAs were found to be downregulated. The dysregulated expression of 5 candidate miRNAs, including miR-31-3p, miR-147b, miR-6736-3p, miR-3065-5p, and miR-3921, were verified by quantitative RT-PCR in the validation set. Among these miRNAs, miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 had 551 target gene intersections. The GO and KEGG Pathway analyses Revealed that miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 may participate in multiple pathophysiological processes, such as foreign substance metabolism and chemical carcinogenesis.The profile of differentially expressed miRNAs was successfully screened, and 4 miRNAs (i.e., miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921) appeared to be involved in gastric carcinogenesis. These might serve as promising biomarkers for gastric cancer.

Asunto(s)

RESUMEN

A new type of coronavirus-induced pneumonia eventually termed "coronavirus disease 2019" (COVID-19) was diagnosed in patients in Wuhan (Hubei Province, China) in December 2019, and soon spread worldwide. To improve the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we analyzed the results of viral nucleic acid and serum-specific antibody tests on clinical samples from 20 patients with SARS-CoV-2 infection diagnosed at the First Affiliated Hospital of Guangzhou Medical University in China. By comparing various sample types collected from COVID-19 patients, we revealed multiple pathways for SARS-CoV-2 shedding, and a prolonged detectable period for viral nucleic acid test in sputum specimens, demonstrating that the timeline of the viral shedding is of great value in determining the time of release from quarantine or discharge from hospital. We also recommend for the application of serological test to assist in confirming SARS-CoV-2 infection judged by viral nucleic acid test, especially when COVID-19-related symptoms have appeared and the viral nucleic acid test was negative. Our findings are critical for the diagnosis of SARS-CoV-2 infection and for determining deadline of restriction measures to prevent transmission caused by convalescent patients with COVID-19.

Asunto(s)

RESUMEN

CXC chemokine receptor 4 (CXCR4) is a co-receptor for HIV-1 entry into target cells. Its natural ligand, the chemokine SDF-1, inhibits viral entry mediated by this receptor. However, the broad expression pattern of CXCR4 and its critical roles in various physiological and pathological processes indicate that the direct application of SDF-1 as an entry inhibitor might have severe consequences. Previously, we constructed an effective SDF-1 mutant, SDF-1/54, by deleting the α-helix of the C-terminal functional region of SDF-1. Of note, SDF-1/54 shows remarkable decreased chemotoxic ability, but maintains a similar binding affinity to CXCR4, suggesting SDF-1/54 might better serve as a CXCR4 inhibitor. Here, we found that SDF-1/54 exhibited potent antiviral activity against various X4 HIV-1 strains, including the infectious clone HIV-1 NL4-3, laboratory-adapted strain HIV-1 IIIB, clinical isolates and even drug-resistant strains. By using time-of-addition assay, non-infectious and infectious cell-cell fusion assay and CXCR4 internalization assay, we demonstrated SDF-1/54 is an HIV-1 entry inhibitor. A combination of SDF-1/54 with several antiretroviral drugs exhibited potent synergistic anti-HIV-1 activity. Moreover, SDF-1/54 was stable and its anti-HIV-1 activity was not significantly affected by the presence of seminal fluid, vaginal fluid simulant and human serum albumin. SDF-1/54 showed limited in vitro cytotoxicity to lymphocytes and vaginal epithelial cells. Based on these findings, SDF-1/54 could have a therapeutic potential as an HIV-1 entry inhibitor.

Asunto(s)

RESUMEN

The purpose of this study was to investigate the expression profile of circular RNA (circRNA) in gastric cancer cells MGC-803, SGC-7901 and NCI-N87 with different degrees of differentiation and normal gastric epithelial cells GES-1. High throughput circRNA microarray technique was used to detect the differential expression of circRNA between three kinds of differentiated gastric cancer cells and normal gastric epithelial cells. The interaction of microRNAs (miRNAs) with circRNAs was predicted by bioinformatics software, and circRNA, which might have great significance in gastric cancer, was identified by literature search. The results showed that there were 79 up-regulated circRNAs and 229 down-regulated circRNAs in gastric cancer cells with different degrees of differentiation compared with those in normal gastric epithelial cells. Through bioinformatics software analysis and literature retrieval, it was found that hsa_circ_0001897 was related to the staging and metastasis of gastric cancer, while the miR-150-5p, which combined with it, was closely related to many kinds of digestive tract tumors, such as colon cancer, liver cancer, and cholangiocarcinoma. The miR-16-5p, which has binding sites with hsa_circ_0008106 and hsa_circ_0060456, has been confirmed to be involved in the development of gastric cancer. The above results suggest that hsa_circ_0001897, hsa_circ_0008106 and hsa_circ_0060456 may be closely related to the occurrence and development of gastric cancer by interacting with miRNA.

Asunto(s)