发布日期:2020-12-31 15:32:03浏览次数:3436
本周Countstar在应用发表的文献中选取了6篇分享给大家。第1篇是关于中草药药理方面,阐述了补骨脂素对于肝毒性的影响。第2篇文章介绍了多发性骨髓瘤的发病机理,骨髓瘤中非编码RNA DARS-AS1被缺氧诱导因子(HIF)-1直接调节,为我们理解多发性骨髓瘤提供了更多的机制基础。第3、4篇文章分别介绍了肺癌、结直肠癌各自癌细胞的调控机理。第5、6两篇文章是在新型的化学材料上进行了研究,为解决疾病提供新的辅助工具。感兴趣的文章可以去寻找一下原文。
1.The Accumulation of Psoralen Contributes to ItsHepatotoxicity Revealed by Pharmacokinetic and Toxicokinetic Study afterRepeated Administration
通过药代动力学和毒代动力学研究表明补骨脂素的积累是引起肝毒性的原因。
ABSTRACT: Psoralen is afuranocoumarin compound found in many herb medicines and is claimed tocontribute to the hepatotoxicity caused by lots of traditional Chinesemedicine. So far, there has been no research on the difffferences inpharmacokinetics of single and repeated dosing of psoralen. Moreover, theresearch on the cumulative toxicity of low concentration and long-termadministration on cells has not been reported. Therefore, this studyinvestigated the pharmacokinetic difffferences and the accumulated cytotoxicityof psoralen from repeated administration. The study found that after single orrepeated administration of psoralen for 3 months at various dosages (14, 28, and56 mg/kg), the pharmacokinetic parameters of female rats between single doseand repeated dose administration are totally difffferent. Compared with asingle administration, multiple administrations increased psoralen’s in vivoexposure, prolonged the peak time, prolonged the half-life of the drug, reducedthe drug clearance rate, and prolonged the drug’s stay in the body. HepG2 cellswere exposed to low doses (5, 10, 20, or 40 μM) of psoralen for 1, 2, 3, or 4days. A 20 and 40 μM dose of psoralen did not induced cell death in the 1st daybut signifificantly decreased the cell viability at the 3rd and 4th day ofrepeated administration, respectively. In addition, multiple administrations ofpsoralen decreased cell viability due to G2 arrest.
缺氧诱导RNA DARS-AS1调节RBM39稳定性促进骨髓瘤
ABSTRACT: Multiple myeloma is amalignant plasma-cell disease, which is highly dependent on the hypoxic bonemarrow microenvironment.However, the underlying mechanisms of hypoxiacontributing to myeloma genesis are not fully understood. Here, we show that longnoncoding RNA DARS-AS1 in myeloma is directly upregulated by hypoxia induciblefactor (HIF)-1. Importantly, DARS-AS1 is required for the survival andtumorigenesis of myeloma cells both in vitro and in vivo. DARS-AS1 exerts itsfunction by binding RNA-binding motif protein 39 (RBM39),which impedes theinteraction between RBM39 and its E3 ubiquitin ligase RNF147, and preventsRBM39 from degradation. The overexpression of RBM39 observed in myeloma cellsis associated with poor prognosis.Furthermore, knockdown of DARS-AS1 inhibitsthe mammalian target of rapamycin signaling pathway, an effect that is reversedby RBM39 overexpression. We reveal that a novel HIF-1/DARS-AS1/RBM39 pathway isimplicated in the pathogenesis of myeloma. Targeting DARS-AS1/RBM39 may,therefore,represent a novel strategy to combat myeloma.
非编码RNA HOTAIR作为miR-149-5p的竞争性内源RNA,促进非小细胞肺癌细胞的生长、迁移和侵袭
ABSTRACT: Lung cancer is a leadingcause of cancer death all around the world. Long non-coding RNAs (lncRNAs) havebeen confirmed to be involved in carcinogenesis of malignancies.However, themolecular mechanism of most lncRNAs in various kinds of cancers remainsunclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role innon-small cell lung cancer, and the overexpression of HNRNPA1 is shown topromote the proliferation of lung adenocarcinoma cells. In our study, we findthat the overexpression of HOTAIR could promote the proliferation and overexpressionof miR-149-5p could inhibit the proliferation of lung cancer cells. Flowcytometric analysis determines that overexpression of miR-149-5p induces cellcycle arrest in the G0/G1
phases, whereas overexpression ofHOTAIR decreases the proportion of G0/G1phase cells. Also, overexpression ofHOTAIR promotes the migration and invasion ability of lung cancer cells,confirmed by the wound-healing and transwell assays, which are suppressed byoverexpression of miR-149-5p. Furthermore, the dual-luciferase reporter assayindicates that miR-149-5p could bind both HOTAIR and the 3′UTR of HNRNPA1.Insummary, we find that HOTAIR can regulate HNRNPA1 expression through a ceRNAmechanism by sequester miR-149-5p, which post-transcriptionally targetsHNRNPA1,thus promoting lung cancer progression.
通过转录因子EBF1过度表达调控PNO1/p53通路抑制结直肠癌的体内外肿瘤生长
ABSTRACT: Early B cell factor 1(EBF1) has been identified as an upstream transcription factor of the potentialoncogene PNO1 and is involved in the growth of colorectal cancer (CRC) cells.However, its expression, biological function, and underlying mechanism ofaction in most solid tumors remain largely unknown. We postulated that EBF1 hasa role in the pathophysiology of CRC. Analysis of EBF1 mRNA expression in CRCtumor samples from several public databases and directly from banked tissuesrevealed that EBF1 mRNA expression is lower in CRC tissue compared tonon-cancerous colorectal tissue. Survival analysis of multiple datasetsrevealed that low EBF1 expression was correlated with shorter overall survival,relapse-free survival, and event-free survival in CRC patients. Transduction oflentivirus encoding full length EBF1 followed by in vitro and in vivo assaysdemonstrated that EBF1 over-expression in CRC cell lines suppresses cell growthby inhibiting cell viability, cell survival, and induces cell cycle arrest andapoptosis. Mechanistic investigation indicated that EBF1 over-expressiondown-regulates PNO1 mRNA and protein expression, as well as transcriptionalactivity while up-regulating the expression of p53 and p21 proteins. Thesefindings suggest that EBF1 is a novel potential tumor suppressor in CRC withprognostic value for the identification of patients at high-risk of relapse.
ABSTRACT: Due to their extraordinaryphysical and chemical properties, MoS2 nanosheets (MSNs) are becoming morewidely used in nanomedicine. However, their influence on immune systems remainsunclear.Two few-layered MSNs at sizes of 100–250 nm (S-MSNs) and 400–500 nm(L-MSNs) were used in this study. Bone marrow-derived dendritic cells (DCs)were exposed to both MSNs at different doses (0, 8, 16, 32, 64, 128 µg/mL) for48 h and subjected to analyses of surface marker expression, cytokinesecretion, lymphoid homing and in vivo T cell priming.Few-layered MSNs rangingfrom 100 to 500 nm in size could play an immunostimulatory role in enhancing DCmaturation, migration and T cell elicitation,making them a good candidate forvaccine adjuvants. Investigation of this study will not only expand theapplications of MSNs and other new transition metal dichalcogenides (TMDCs) butalso shed light on the in vivo immune-risk evaluation of MSN-basednanomaterials.
6.Encapsulation and release of living tumor cellsusing hydrogels with the hybridization chain reaction
Countstar Fluorescence Cell Analyzer