HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms.Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo.Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo.Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.     

Plant litter quality regulates soil eco-enzymatic stoichiometry and microbial nutrient limitation in a citrus orchard

Plant and Soil - The impacts associated with litter decomposition in intensive cropping on eco-enzymatic stoichiometry and microbial nutrient limitation are still under debate. To evaluate the...     

Genetic diversity of mitochondrial D-LOOP sequences in the spotted scat (Scatophagus argus) from different geographical populations along the northern coast of the South China Sea

The genetic diversity of 289 spotted scat (Scatophagus argus) from seven populations along the northern coast of the South China Sea was studied by analyzing the full-length sequences of the mitochondrial control region (D-LOOP). The S. argus D-LOOP sequence was 1,004–1,010 bp long and contained 156 variant sites. The seven studied S. argus populations had a high degree of genetic diversity (haplotype diversity [Hd] = 0.99135; nucleotide diversity (π) = 0.01313). There was no obvious genetic differentiation among the seven geographical populations and gene exchange was frequent (Fst = −0.01867–0.01117, p > .05). Four distinct mitochondrial lineages were identified in the phylogenetic tree and the haplotype network. The between-lineage Fst was 0.71690–0.84940 (p < .001), but these lineages showed no obvious phylogeographic pattern. Based on D-LOOP mutation rates, we estimated that the four lineages diverged approximately 513,800–93,600 years ago, during the Eocene ice age, at which time falling sea levels may have led to population segregation. We estimated that S. argus population expansion occurred approximately 2.29–0.68 million years ago, during the late Pleistocene. During this period, sea levels rose again, allowing previously separated lineages to come into sympatry, which eventually gave rise to a highly genetically diverse population without pyhlogeographic structure. Here, we characterized the genetic structure and differentiation of seven S. argus populations from the northern coast of the South China Sea. Our results suggested that the seven S. argus populations from the northern coast of the South China Sea have a relatively low level of genetic variation and can be considered a single unit for the purposes of fishery development, utilization, and management.     

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain

Cellular and Molecular Neurobiology - Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation....     

编辑MSTN半胱氨酸节基元促进两广小花猪肌肉生长

肌生长抑制素(myostatin,MSTN)是转化生长因子β(transforming growth factor-β,TGF-β)家族成员之一,是一种肌肉生长抑制因子。解除MSTN的生长抑制功能是提高畜禽肌肉产量的一种有效途径。TGF-β的半胱氨酸节结构基元(cystine knot motif)能够稳定MSTN蛋白结构,对MSTN生物学功能的发挥具有重要调控作用。本研究应用CRISRP/Cas9基因编辑技术在两广小花猪肾细胞(Liang Guang small spotted pig kidney cells,LPKCs)中对MSTN基因外显子3进行编辑,破坏了其半胱氨酸节基元,以解除MSTN对靶基因的抑制功能。将流式分选获得的混合阳性MSTN编辑LPKCs作为供体细胞进行核移植和胚胎移植,获得8头MSTN基因编辑两广小花猪仔猪,其中2头存活至10日龄,经鉴定这2头均为基因编辑杂合子,它们在构成MSNT蛋白半胱氨酸节基元的两个半胱氨残基C106和C108编码序列附近分别发生碱基的缺失与替换,导致移码突变,使C106和C108突变为其他氨基酸。MSTN基因编辑两广小花猪杂合子肩部和臀部肌肉较为发达。H&E切片分析显示,MSTN基因编辑猪肌纤维横截面积显著减少,肌纤维数量显著增多。Western Blot分析结果显示,C106和C108缺失对MSTN蛋白表达无显著性影响,但显著促进其靶基因Myf5、MyoD和Myogenin等成肌相关因子的表达。本研究获得的基因编辑猪模型没有造成MSTN表达完全缺失,可保留MSTN其他生物学功能,在促进两广小花猪肌肉生长的同时还消除了MSTN完全缺失可能对小花猪造成的潜在影响。     

Autophagy in Xp11 translocation renal cell carcinoma: from bench to bedside

Molecular and Cellular Biochemistry - Xp11 translocation renal cell carcinoma (tRCC) characterized by the rearrangement of the TFE3 is recently identified as a unique subtype of RCC that urgently...     

Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model

Mycopathologia - Vulvovaginal candidiasis (VVC) caused by Candida spp. affects 70–75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and...