The phosphatase of regenerating liver-3 protein (PRL-3) promotes glioma cell invasiveness by interacting with ß3 -tubulin.

PRL-3 is a tyrosine phosphatase linked with tumor metastasis. It is detected high expression in different kinds of cancers, including colorectal, gastric, ovarian, and liver cancer. Its high expression is positively correlated with the progression of tumors and negatively with survivals of patients. However, the detailed mechanism underlying PRL-3 in tumor metastasis still remains unclear. In the present study, we found that PRL-3 is able to bind to ß3-tubulin in pull-down and co-immunoprecipitation assays. Furthermore, overexpression of PRL-3 dephosphorylated ß3-tubulin, a component of cytoskeleton, which plays critical role in cell shape formation and migration. Using cell wound healing and matrigel invasion assays, we found that PRL-3 could promote the migration and invasion of glioma cells. Taken together, our study revealed that PRL-3 may be involved in migration and invasion of glioma by dephosphorylating ß3-tubulin. It is tempting to speculate that dephosphorylation of ß3-tubulin by PRL-3 results in assembly of the cytoskeleton and facilitates cell migration and/or tumor metastasis.

lncRNA MALAT1 Promotes Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-2355-3p/IL6ST Axis.

Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Size-dependent dynamic stability analysis of the cantilevered curved microtubule-associated proteins (MAPs).

A pathway to the design of even more effective versions of the powerful anti-cancer drug Taxol is opened with the most detailed look ever at the dynamic and static behaviors of MAPs. Regarding this issue, the dynamic stability analysis of cantilevered microtubules in axons with attention to different size effect parameters based on the generalized differential quadrature method is presented. Supporting the effects of MAP Tau proteins and surrounding cytoplasm are considered as an elastic foundation. The better understanding modeled as a moderately thick curved cylindrical nanoshell. The real property of the living biological cells is presented as the Kelvin-Voight viscoelastic properties. Hamilton's principle is employed to establish the Clamped-Free boundary conditions and governing equations, which is finally solved by the Fourier-expansion based generalized differential quadrature method (FGDQM). Considering length scale and nonlocal parameters (l = 3h, µ=h/2) in nonlocal strain gradient theory (NSGT) leads to a better agreement with experimental results in comparison by other theories that in the results section is presented, in details. Based on presented semi-numerical results, for a specific value of the cantilevered microtubule length, the influence of the Kw parameter on the amplitude of MAPs is much more considerable, that should be attention to this value. Another important consequence is that when the property of the MAPs is not considered viscoelastic, the relation between axial load and frequency of the living structure is nonlinear but by considering the time-dependent viscoelastic property the relation could be linear.Communicated by Ramaswamy H. Sarma.

LncRNA HCG11 Inhibits Adipocyte Differentiation in Human Adipose-Derived Mesenchymal Stem Cells by Sponging miR-204-5p to Upregulate SIRT1.

Long noncoding RNAs (lncRNAs) have been discovered to play a key role in adipogenesis, while the role of lncRNA human leukocyte antigen complex group 11 (HCG11) in adipocyte differentiation has not been studied clearly. We used human adipose-derived mesenchymal stem cells (hAdMSCs) to establish a model of cell differentiation in vitro and found that expression of lncRNA HCG11 was decreased during adipogenesis through real-time quantitative polymerase chain reaction analysis. Then, hAdMSCs were transfected with pcDNA-HCG11 or HCG11-shRNA (sh-HCG11); the adipogenic marker proteins were detected by Western blot, and the activity of lipogenesis enzymes was detected by spectrophotometry. The expression of CCAAT-enhancer-binding protein α, fatty acid-binding protein, peroxisome proliferator-activated receptor gamma 2 and the levels of acetyl coenzyme A carboxylase and fatty acid synthase FAS were significantly downregulated in hAdMSCs at different stages transfected with pcDNA-HCG11, while knockdown of lncRNA HCG11 promoted adipocyte differentiation. Bioinformatic analysis indicated that miR-204-5p was a potential target gene of HCG11, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. In addition, miR-204-5p directly targeting the 3'-untranslated region of SIRT1 was also predicted by StarBase and verified by luciferase reporter gene analysis. Enforced expression of miR-204-5p negatively regulated the SIRT1 protein level. Furthermore, SIRT1 overexpression significantly inhibited adipogenic marker protein, levels of lipogenesis enzymes, and the proliferation of hAdMSCs. When pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that the miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Taken together, we found that HCG11 negatively regulated cell proliferation and adipogenesis by the miR-204-5p/SIRT1 axis. Our findings might provide a new target for the study of adipogenesis in hAdMSCs and obesity.

Bilobalide protects mitochondrial function in ovariectomized rats by up-regulation of mRNA and protein expression of cytochrome c oxidase subunit I.

Bilobalide (BB), a sesquiterpene trilactone from Ginkgo biloba has been proposed to have protective effects on mitochondrial function. Using ovariectomized rats to mimic the post-menopausal pathophysiological changes in women, this study demonstrated that BB treatment could prevent estrogen withdrawal-induced decrease in mitochondrial adenosine triphosphate content, cytochrome c oxidase subunit I (COXI) mRNA and protein levels and COX activity in hippocampal tissues as effectively as estradiol benzoate. But neither ovariectomy nor BB treatment affected citrate synthase activity. These results suggested that BB was able to regulate COX activity via up-regulation of the gene and protein expression of its mitochondrial DNA-coded subunits, and modulation of COX activity by BB might contribute to its protective effects on mitochondrial function. Given that ovariectomy induces decrease in estrogen levels similar to that of menopause, BB may be useful in developing therapy for neurodegenerative diseases such as Alzheimer's disease in post-menopausal females.

Postmortem MRI changes of the brains of the rats of different ages.

Brain degenerative changes were studied in the rats of different ages after cervical dislocation by T(2) MRI and histology. Appearance of dark spots in the T(2) images increased with increased duration after death. Quantitative analysis of the density of these spots revealed that the neonatal (1 week) and the old (9 months) animals had accelerated degenerative changes when compared with the young adult (1 month). The degenerative changes correlated with the accumulation of vacuoles or spaces in the brain tissue histologically. This study pointed out not only brain degenerative changes after death were associated with age, it also revealed that the MRI T(2) evaluations could be used as a way in postmortem investigation.

Possible role of mitochondrial dysfunction in central neurodegeneration of ovariectomized rats.

In the present study, ovariectomized Sprague-Dawley rats were used to mimic the pathological changes of post-menopausal females with genistein and estradiol benzoate (EB) as substitutes for endogenous estradiol. Measurements of hippocampal ATP content, mitochondrial ATP content and the rate of mitochondrial ATP synthesis in the hippocampus indicated that after ovariectomy, brain energy metabolism of the rats presented a transient change in hippocampal ATP content which was significant from the 6th to the 8th day after ovariectomy. The change on the 6th day was the most noteworthy. Mitochondrial ATP content and the rate of mitochondrial ATP synthesis of the hippocampus were also lowered. However, after using EB or genistein, the three indicators returned to normal. It is suggested that mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) of the post-menopausal female, and may serve as the target for endogenous estrogen and exogenous phytoestrogen. In addition, genistein, which possesses the properties of estrogen but not its side effects such as carcinogenicity, could reverse the bioenergetic defects of ovariectomized rats and perhaps be used as a substitute for estradiol to prevent or treat central neurodegeneration in post-menopausal women.