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  • Baker posted an update 7 months, 1 week ago

    Metastasis is the main cause of cancer-related death and the major challenge in cancer treatment. Cancer cells in circulation are termed circulating tumor cells (CTCs). Primary tumor metastasis is likely due to CTCs released into the bloodstream. These CTCs extravasate and form fatal metastases in different organs. Analyses of CTCs are clarifying the biological understanding of metastatic cancers. These data are also helpful to monitor disease progression and to inform the development of personalized cancer treatment-based liquid biopsy. However, CTCs are a rare cell population with 1-10 CTCs per ml and are difficult to isolate from blood. Numerous approaches to detect CTCs have been developed based on the physical and biological properties of the cells. The present review summarizes the progress made in detecting CTCs.Ubiquitin-specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin-like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. Bemnifosbuvir in vivo However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non-cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, in vitro analysis revealed that USP18-knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18-knockdown increased the levels of Bcl-2, STAT3 and phosphorylated-ERK in HeLa cells. Notably, USP18 silencing-induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor-associated biological behaviors, which are associated with the ERK signaling pathway.Vascular calcification (VC) accompanies the trans-differentiation of vascular smooth muscle cells (VSMCs) into osteo/chondrocyte-like cells and resembles physiological bone mineralization. However, the molecular mechanisms underlying VC initiation and progression have remained largely elusive. The aim of the present study was to identify the genes and pathways common to VSMC and osteoblast calcification and construct a regulatory network of non-coding RNAs and transcription factors (TFs). To this end, the Gene Expression Omnibus dataset GSE37558 including mRNA microarray data of calcifying VSMCs (CVSMCs) and calcifying osteoblasts (COs) was analyzed. The differentially expressed genes (DEGs) were screened and functionally annotated and the microRNA (miRNA/mRNA)-mRNA, TF-miRNA and long non-coding RNA (lncRNA)-TF regulatory networks were constructed. A total of 318 DEGs were identified in the CVSMCs relative to the non-calcified VSMCs, of which 43 were shared with the COs. The CVSMC-related DEGs were mainly enrther, the CVSMCs and COs exhibited similar molecular changes in the ECM. In addition, the MELK-FOXM1, H19/DANCR-FOXO1 and SNAI2 regulatory pathways likely mediate VSMC calcification.Xiaochaihu decoction is one of the most important traditional Chinese medicines that is widely used with other drugs in clinical practice, and may cause drug-drug interactions. However, there is not sufficient experimental evidence for the effects of Xiaochaihu decoction on cytochrome P450s (CYPs). The aim of the present study was to investigate the effects of Xiaochaihu decoction on the mRNA and protein levels of hepatic CYPs. Eighty normal male Sprague-Dawley (SD) rats were randomly divided into two groups based on body weight and duration of drug administration (3 and 6 days). Each group was further divided into subgroups Control group (2 ml 5‰ CMC-Na); hepatic enzyme inducer group (50 mg/kg/day rifampicin); and experimental groups (Xiaochaihu decoction Low dose, 1.7 g/kg/day; medium dose, 3.4 g/kg/day; high dose, 6.8 g/kg/day). The effects of Xiaochaihu decoction on Cyp1a2, Cyp3a1, Cyp2d6, and Cyp1b1 mRNA and protein expression in rats were evaluated using reverse transcription quantitative reverse transcription polymerase chain reaction and western blot analysis. After 3 days, medium dose of Xiaochaihu decoction inhibited the mRNA and protein expression of Cyp1a2, Cyp3a1 and Cyp1b1. In addition, after 6 days, Xiaochaihu decoction induced Cyp3a1 mRNA expression at low and medium doses; Cyp2d6 mRNA expression at low and high doses; and Cyp2d6 protein expression at high doses. Nonetheless, the gene and protein expression of Cyp1b1 was not affected at any dose. The findings of the present study may provide insights into potential drug-drug interactions associated with Xiaochaihu decoction.Resveratrol is a natural polyphenol with multiple positive biofunctions and was found to have potential as a radiosensitizer with an intricate molecular mechanism. Store-operated calcium entry (SOCE) is a novel intracellular calcium regulatory pattern that is mainly mediated by iron channels, such as by the stromal interaction molecule (STIM) and calcium release-activated calcium channel protein (Orai) families. SOCE was recently reported to be suppressed via the downregulation of STIM or Orai families for the promotion of tumor cell death induced by resveratrol. In the present study, resveratrol combined with irradiation treatment were found to induce more evident cell damage compared with irradiation treatment alone, as shown with Cell Counting Kit-8 assay and mitochondrial membrane potential detection with rhodamine 123. Additionally, resveratrol combined with irradiation treatment decreased the expression of STIM1 and Orai1, while it had no effects on STIM2, Orai2 and Orai3. Moreover, resveratrol combined with irradiation treatment lead to alleviated thapsigargin-induced SOCE.

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