CtIP interacts with a group of tumor suppressor proteins including RB (retinoblastoma protein), BRCA1, Ikaros, and CtBP, which regulate cell cycle progression through transcriptional repression as well as chromatin remodeling. However, how CtIP exerts its biological function in cell cycle progression remains elusive. To address this issue, we generated an inactivated Ctip allele in mice by inserting a neo gene into exon 5. The corresponding Ctip ؊/؊ embryos died at embryonic day 4.0 (E4.0), and the blastocysts failed to enter S phase but accumulated in G 1 , leading to a slightly elevated cell death. Mouse NIH 3T3 cells depleted of Ctip were arrested at G 1 with the concomitant increase in hypophosphorylated Rb and Cdk inhibitors, p21. However, depletion of Ctip failed to arrest Rb ؊/؊ mouse embryonic fibroblasts (MEF) or human osteosarcoma Saos-2 cells at G 1 , suggesting that this arrest is RB dependent. Importantly, the life span of Ctip ؉/؊ heterozygotes was shortened by the development of multiple types of tumors, predominantly, large lymphomas. The wild-type Ctip allele and protein remained detectable in these tumors, suggesting that haploid insufficiency of Ctip leads to tumorigenesis. Taken together, this finding uncovers a novel G 1 /S regulation in that CtIP counteracts Rbmediated G 1 restraint. Deregulation of this function leads to a defect in early embryogenesis and contributes, in part, to tumor formation.

miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules Cyclin D1 and c‐Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR‐375‐3p also showed a significant inhibitory effect in vivo in bladder tumor‐bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR‐375‐3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.

Natural killer cells, one of the important types of innate immune cells, play a pivotal role in the antiviral process in vivo. It has been shown that increasing NK cell activity may promote the alleviation of viral infections, even severe infection-induced sepsis. Given the current state of the novel coronavirus (SARS-CoV-2) global pandemic, clarifying the anti-viral function of NK cells would be helpful for revealing the mechanism of host immune responses and decipher the progression of COVID-19 and providing important clues for combating this pandemic. In this review, we summarize the roles of NK cells in viral infection and sepsis as well as the potential possibilities of NK cell-based immunotherapy for treating COVID-19.

Nowadays, tumor has been the serious threat to human health and life. To further explore the mechanism of tumor genesis and development is necessarily for developing the effective treatment strategy. Extracellular vesicles are the vesicles secreted by almost all types of cells, and they play an important part in intercellular communication by transporting their cargoes. Immune cells are the vital components of the human defense system, which defense against infection and tumor through cytotoxicity, immune surveillance, and clearance. However, via release tumor-derived extracellular vesicles, tumor could induce immune cells dysfunction to facilitate its proliferation and metastasis. Studies have shown that tumor-derived extracellular vesicles play dual role on immune cells by their specific cargoes. Here, we reviewed the effects of tumor-derived extracellular vesicles on immune cells in recent years and also summarized their research progress in the tumor immunotherapy and diagnosis.

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The magnetic field is the most common element in the universe, and high static magnetic field (HiSMF) has been reported to act as an inhibited factor for osteoclasts differentiation. Although many studies have indicated the negative role of HiSMF on osteoclastogenesis of RANKL-induced RAW264.7 cells, the molecular mechanism is still elusive. In this study, the HiSMF-retarded cycle and weakened differentiation of RAW264.7 cells was identified. Through RNA-seq analysis, RANKL-induced RAW264.7 cells under HiSMF were analysed, and a total number of 197 differentially expressed genes (DEGs) were discovered. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that regulators of cell cycle and cell division such as Bub1b, Rbl1, Ube2c, Kif11, and Nusap1 were highly expressed, and CtsK, the marker gene of osteoclastogenesis was downregulated in HiSMF group. In addition, pathways related to DNA replication, cell cycle, and metabolic pathways were significantly inhibited in the HiSMF group compared to the Control group. Collectively, this study describes the negative changes occurring throughout osteoclastogenesis under 16 T HiSMF treatment from the morphological and molecular perspectives. Our study provides information that may be utilized in improving magnetotherapy on bone disease.

Background Propofol and sevoflurane are two commonly used perioperative anesthetics. Some studies have found that these anesthetic drugs affect tumorigenesis. Previous studies have mostly focused on in vitro experiments, and the specimens collected were mainly peripheral body fluids, lacking direct evidence of the impact of anesthetic drugs on human tissues. This study aimed to elucidate the effects of propofol and sevoflurane on lung cancer using next-generation sequencing through an in vivo experiment. Methods Patients were randomly assigned to a group receiving either propofol or sevoflurane during surgery. Then, the patients’ tumor and paired normal samples were collected and sequenced by next-generation sequencing. Differentially expressed genes (DEG) were analyzed by two statistical models, followed by cluster analysis, PCA, Gene Ontology, and KEGG pathway analysis. Candidate genes were confirmed by qRT–PCR. Results The demographic data of the two study groups were not statistically significant. Through single-factor model analysis, 810 DEG in the propofol group and 508 DEG in the sevoflurane group were obtained. To better reflect the differential effects between propofol and sevoflurane while reducing the false-positive DEG, we used multifactor model analysis, which resulted in 124 DEG. In PCA and cluster analysis, four groups (propofol cancer group, propofol normal group, sevoflurane cancer group, sevoflurane normal group) were separated adequately, indicating the accuracy of the analysis. We chose seven significant pathways (cellular response to interleukin-1, chemokine-mediated signaling pathway, chemokine signaling pathway, cytokine–cytokine receptor interaction, inflammatory response, immune response, and TNF signaling pathway) for downstream analysis. Based on the pathway analysis, three candidate genes (CXCR1, CXCL8, and TNFAIP3) were chosen, and their qRT–PCR results were consistent with the sequencing results. Conclusions Through RNA-seq analysis, the effects of propofol and sevoflurane during lung cancer resection were different, mainly in inflammatory-related pathways, which might be possibly by targeting CXCL8. Trial registration Trial registry number was ChiCTR1900026213.

Background: Propofol and sevoflurane are two commonly used anesthetics perioperatively. It showed that anesthetic drugs may have an effect on tumorigenesis. Previous researches mostly focused on in vitro experiments, the specimens collected were mostly peripheral body fluid, lacking direct evidence of the impact of anesthetic drugs on human tissues. This study aims at elucidating the effects of propofol and sevoflurane on lung cancer using next-generation sequencing through an in vivo experiment. Methods: Patients were randomly assigned to a group either receiving propofol or sevoflurane during surgery. Then patients’ tumor and paired normal samples were collected and sequenced by next-generation sequencing. Differentially expressed genes (DEG) were analyzed by two statistical models, then cluster analysis, PCA, GO ontology and KEGG pathways analysis were done. Candidate genes were confirmed by qRT-PCR. Results: Two study groups demographic data were not statistically significant. Through single factor model analysis, 810 DEG in propofol group and 508 DEG in sevoflurane group were obtained. In order to better reflect the differential effects of propofol and sevoflurane, in the meanwhile reduce false positives of DEG, we used multi-factor model analysis, which resulted in 124 DEG. In PCA and cluster analysis, four groups (propofol cancer group, propofol normal group, sevoflurane cancer group, sevoflurane normal group) were separated adequately, indicating the accuracy of DEG. We chose seven significant pathways (Cellular response to interleukin-1, Chemokine-mediated signaling pathway, Chemokine signaling pathway, Cytokine-cytokine receptor interaction, Inflammatory response, Immune response, TNF signaling pathway) for downstream analysis. From qRT-PCR results, three genes (CXCR1, CXCL8 and TNFAIP3) were confirmed. Conclusions: Through RNA-seq analysis, the effects of propofol and sevoflurane during lung cancer resection were different, and mainly differ in inflammatory related pathways which might be possibly by targeting CXCL8.Trial registration: Trial registry number was ChiCTR1900026213 (http://www.chictr.org.cn/showproj.aspx?proj=43733).