The role of exosomal miR-375-3p: A potential suppressor in bladder cancer via the Wnt/ß-catenin pathway.

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/ß-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.

The role of NK cells in fighting the virus infection and sepsis.

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.

Perioperative Dexmedetomidine Reduces Delirium in Elderly Patients after Lung Cancer Surgery.

BACKGROUND: Delirium, which is one of the most disturbing postoperative complications in elderly patients, shows high morbidity in patients undergoing lung cancer surgery. Dexmedetomidine (DEX) is considered a potential prophylactic agent for preventing patients' delirium after lung cancer surgery. SUBJECTS AND METHODS: Medical records of lung cancer patients over 65 years old with radical pulmonary resection at Henan Provincial People's Hospital from January 2015 to December 2017, China, were evaluated. Patients, care-providers, and investigators were all blinded to group assignment. DEX was administered in the preoperative and intraoperative periods. The incidence of delirium was calculated based on the Intensive Care Delirium Screening Checklist (ICDSC). Scores of ≥4 and 1-3 points represent the diagnoses of delirium and a pre-delirious state, respectively. RESULTS: During postoperative day 1 (POD 1) to POD 7, delirium occurs in both groups. During postoperative POD 1 to POD 7, the incidence of delirium is lower in the DEX group than that in the control group. Furthermore, there are more mild delirium patients but fewer moderate and severe delirium patients in the DEX group compared with the control group. Finally, patients in the DEX group have a shorter duration of delirium, lower numeric pain rating scale during movement and better sleep quality. CONCLUSION: Preoperative and intraoperative application of DEX can reduce the incidence and intensity of delirium after pulmonary resection in elderly patients with lung cancer.

Extracellular Vesicles - Advanced Nanocarriers in Cancer Therapy: Progress and Achievements.

Extracellular vesicles (EVs) are a class of cell-derived, lipid bilayer membrane composed vesicles, and some of them such as exosomes and ectosomes have been proven, playing remarkable roles in transmitting intercellular information, and being involved in each property of cell physiological activities. Nowadays, EVs are considered as potential nanocarriers which could partially resolve the problems of current chemotherapy because of their distinctive advantages. As endogenous membrane encompassed vesicles with nanosize, EVs are able to pass through the natural barriers with prolonged circulation time in vivo and have intrinsic cell targeting properties, they are less toxic, and less immunogenic. Recently, studies focusing on EV-based drug delivery system for cancer therapy have exploded dramatically. This review aims to outline the current applications of EVs as potential nanosized drug carriers in cancer therapy. Firstly, the characteristics and biofunctions of each EV subtype are described. Then the variety of therapeutic cargoes, the loading methods, and the targeting strategy of engineered EVs are emphatically introduced. Thereafter the pros and cons of EVs applied as therapeutic carriers, as well as the future prospects in this field, are discussed.

Transcriptome Analysis Reveals the Negative Effect of 16 T High Static Magnetic Field on Osteoclastogenesis of RAW264.7 Cells.

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.

Exosomes: Versatile Nano Mediators of Immune Regulation.

One of many types of extracellular vesicles (EVs), exosomes are nanovesicle structures that are released by almost all living cells that can perform a wide range of critical biological functions. Exosomes play important roles in both normal and pathological conditions by regulating cell-cell communication in cancer, angiogenesis, cellular differentiation, osteogenesis, and inflammation. Exosomes are stable in vivo and they can regulate biological processes by transferring lipids, proteins, nucleic acids, and even entire signaling pathways through the circulation to cells at distal sites. Recent advances in the identification, production, and purification of exosomes have created opportunities to exploit these structures as novel drug delivery systems, modulators of cell signaling, mediators of antigen presentation, as well as biological targeting agents and diagnostic tools in cancer therapy. This review will examine the functions of immunocyte-derived exosomes and their roles in the immune response under physiological and pathological conditions. The use of immunocyte exosomes in immunotherapy and vaccine development is discussed.

MicroRNAs: Key Players in Bladder Cancer.

Bladder cancer (BC) is the second highest morbid malignancy of the urinary tract and the fifth most common cancer worldwide. BC is highly malignant with significant morbidity and mortality, especially muscle-invasive BC (MIBC), which has a poor prognosis and frequently recurs after the first resection. Therefore, more sensitive diagnostic tools and effective therapeutic methods are urgently needed. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of protein-coding genes by repressing their translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs play very important roles in regulating genes related to tumorigenesis, tumor development, progression, metastasis and angiogenesis. With the rapid development of high-throughput sequencing technology, an increasing number of miRNAs with aberrant expression between either BC patients and healthy volunteers or between BC tumor tissues and matched peripheral control tissues have been recently examined. The tumor etiopathogenesis must be determined to promote the development of new markers as diagnostic and prognostic tools and targets for bladder tumor therapy, it is therefore vital to elucidate the function of miRNAs with aberrant expression in BC. In the present study, we examined the published data of BC-related miRNAs by reviewing their expression levels, possible functions, potential target genes, related molecular regulatory networks, candidate markers for prognosis and diagnosis, and prospective therapeutic cases, and we summarized the status of research on BC-related miRNAs in recent years.