RESUMEN

Background: Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. Methods: The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Results: Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Conclusion: Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.

Asunto(s)

RESUMEN

BACKGROUND: The pathogenesis of human immunodeficiency virus 1 (HIV-1) infection is so complex that have not been clearly defined, despite intensive efforts have been made by many researchers. MicroRNA (miRNA) as regulation factor in various human diseases may influence the course of HIV-1 infection by targeting mRNAs. Thus, studies combining transcription of posttranscriptional miRNA regulation are required. METHODS: With the purpose of identifying cascaded miRNA-mRNA regulatory relationships related to HIV infection in gene level, the parallel miRNA, and mRNA expression profiles were analyzed to select differential expressed miRNAs and mRNAs. Then, miRNA-mRNA interactions were predicted using 3 data sources and Pearson correlation coefficient was calculated based on the gene expression level for accuracy improvement. Furthermore, the calculation of the regulatory impact factors was conducted to reveal crucial regulators in HIV-1 infection. To give further insight into these transcription factor (TF) regulators, the differentially co-expression analysis was conducted to identify differentially co-expressed links and differential co-expressed genes and the co-expression gene modules were identified using a threshold-based hierarchical clustering method, then modules were combined into a miRNA-TF-mRNA network. RESULTS: A total of 69,126 differentially co-expressed links and 626 differential co-expressed genes were identified. Functional enrichment analysis indicated that these co-expressed genes were significantly involved in immune response and apoptosis. Moreover, according to regulatory impact factors, 5 most influential TFs and miRNA in HIV-1 infection were identified and miRNA-TF-mRNA regulatory networks were built during the computing process. CONCLUSIONS: In our study, a set of integrated methods was generated to identify important regulators and miRNA-TF-mRNA interactions. Parallel profiling analysis of the miRNAs and mRNAs expression of HIV/acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy indicated that some regulators have wide impact on gene regulation and that these regulatory elements may bear significant implications on the underlying molecular mechanism and pathogenesis of AIDS occurrence.

Asunto(s)

RESUMEN

Eucommia ulmoides Oliver is a woody plant with great economic and medicinal value. Its dried bark has a long history of use as a traditional medicinal material in East Asia, which led to many glycosides, such as aucubin, geniposide, hyperoside, astragalin, and pinoresinol diglucoside, being recognized as pharmacologically active ingredients. Uridine diphosphate glycosyltransferases (UGTs) catalyze a glycosyl-transferring reaction from the donor molecule uridine-5'-diphosphate-glucose (UDPG) to the substrate, which plays an important role in many biological processes, such as plant growth and development, secondary metabolism, and environmental adaptation. In order to explore the biosynthetic pathways of glycosides in E. ulmoides, 91 putative EuUGT genes were identified throughout the complete genome of E. ulmoides through function annotation and an UDPGT domain search. Phylogenetic analysis categorized them into 14 groups. We also performed GO annotations on all the EuUGTs to gain insights into their functions in E. ulmoides. In addition, transcriptomic analysis indicated that most EuUGTs showed different expression patterns across diverse organs and various growing seasons. By protein-protein interaction predication, a biosynthetic routine of flavonoids and their glycosides was also proposed. Undoubtedly, these results will help in future research into the biosynthetic pathways of glycoside compounds in E. ulmoides.