Identification of Immune-Related Genes in Sepsis due to Community-Acquired Pneumonia.

BACKGROUND: Immunosuppression has a key function in sepsis pathogenesis, so it is of great significance to find immune-related markers for the treatment of sepsis. METHODS: Datasets of community-acquired pneumonia (CAP) with sepsis from the ArrayExpress database were extracted. Differentially expressed genes (DEGs) between the CAP group and normal group by Limma package were performed. After calculation of immune score through the ESTIMATE algorithm, the DEGs were selected between the high immune score group and the low immune score group. Enrichment analysis of the intersected DEGs was conducted. Further, the protein-protein interaction (PPI) of the intersected DEGs was drawn by Metascape tools. Related publications of the key DEGs were searched in NCBI PubMed through Biopython models, and RT-qPCR was used to verify the expression of key genes. RESULTS: 360 intersected DEGs (157 upregulated and 203 downregulated) were obtained between the two groups. Meanwhile, the intersected DEGs were enriched in 157 immune-related terms. The PPI of the DEGs was performed, and 8 models were obtained. In sepsis-related research, eight genes were obtained with degree ≥ 10, included in the models. CONCLUSION: CXCR3, CCR7, HLA-DMA, and GPR18 might participate in the mechanism of CAP with sepsis.

Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown. METHODS: Quantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay. RESULTS: Here, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217. DISCUSSION: Our results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.

Disulfide-based PEGylated prodrugs: Reconversion kinetics, self-assembly and antitumor efficacy.

The prodrug strategy serves well in drug formulation and delivery. Two disulfide-based PEGylated prodrugs were developed and the drug reconversion upon different conditions were studied in detail. The reconversion-induced oversaturation phenomenon was firstly reported here. We found the prodrug can co-assemble with parent drug via π-π stacking into well-defined nanoparticles. The PEG layer of the self-assembled nanoparticles improved the stability of the PEGylated prodrug by reducing the contact with biological enzymes. The nanoparticles also show favorable antitumor efficacy, both in vitro and in vivo.