Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)-induced hepatorenal damages still remain unknown. In the present study, the data ...manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145–5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145–5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145–5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future.
Proposed signaling mechanism of dioscin on restoring MTX-induced liver and kidney damages via regulating miR-145-5p-mediated oxidative stress. Dioscin up-regulated Sirt5 level by down-regulating miR-145–5p level to adjust the expression levels of Nrf2, HO-1, GCLC, NQO1, Gst, SOD1 and Keap1. Dioscin protected hepatorenal damages caused by MTX via regulating miR-145-5p-mediated oxidative stress. Display omitted
•Dioscin significantly relieved MTX-induced hepatorenal damages in vitro and in vivo.•MTX caused oxidative damages to the liver and kidney in vitro and in vivo.•miR-145–5p directly targeted Sirt5 to adjust oxidative stress.•Dioscin reduced the expression levels of miR-145–5p and suppressed w miR-145-5p-medicated oxidative stress.
Recent genetic and morphologic studies have challenged the traditional view on the pathogenesis of ovarian cancer; suggesting that ovarian cancer predominantly arises within the fallopian tubes or ...the uterus. We hypothesize that surgical removal of the fallopian tubes is associated with a reduced risk for ovarian cancer.
In this population-based cohort study, we used data on women with previous surgery on benign indication (sterilization, salpingectomy, hysterectomy, and bilateral salpingo-oophorectomy BSO, hysterectomy; n = 251465) compared with the unexposed population (n = 5449119) between 1973 and 2009 and analyzed with Cox regression models. The effects of one- and two-sided salpingectomy were considered in a subanalysis. All statistical tests were two-sided.
There was a statistically significantly lower risk for ovarian cancer among women with previous salpingectomy (HR = 0.65, 95% CI = 0.52 to 0.81) when compared with the unexposed population. In addition, statistically significant risk reductions were observed among women with previous hysterectomy (HR = 0.79, 95% CI = 0.70 to 0.88), sterilization (HR = 0.72, 95% CI = 0.64 to 0.81), and hysterectomy with BSO (HR = 0.06, 95% CI = 0.03 to 0.12). Bilateral salpingectomy was associated with a 50% decrease in risk of ovarian cancer compared with the unilateral procedure (HR = 0.35, 95% CI = 0.17 to 0.73, and 0.71, 95% CI = 0.56 to 0.91, respectively).
Salpingectomy on benign indication is associated with reduced risk of ovarian cancer. These data support the hypothesis that a substantial fraction of ovarian cancer arises in the fallopian tube. Our results suggest that removal of the fallopian tubes by itself, or concomitantly with other benign surgery, is an effective measure to reduce ovarian cancer risk in the general population.
MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
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•HI/R injury significantly decreased the expression level of miR-142-3p.•miR-142-3p alleviated apoptosis and inflammation to relieve HI/R injury.•miR-142-3p directly targeted ...MARCKS.•MARCKS siRNA markedly inhibited HI/R injury.
MiR-142-3p as one key molecule in oncogenesis and inflammation plays crucial roles in hepatic fibrosis, hepatocellular carcinoma and other liver disease. However, there have no literatures to report its effects on hepatic ischemia-reperfusion (HI/R) injury. In the present work, hypoxia reoxygenation (H/R) models on AML12 and HepG2 cells, and ischemia/reperfusion model in mice were established. The methods of real-time PCR, dual luciferase reporter, mimic, inhibitor, agomir, antagomir and siRNA transfection assays were used. The expression levels of miR-142-3p were decreased in model groups in vitro and in vivo compared with control group or Sham group, which directly targeted MARCKS to regulate its expression. Then, MARCKS activated p38/JNK signal, up-regulated NF-κB expression to accelerate inflammation, and inhibited PI3K/AKT signal to promote apoptosis. Moreover, miR-142-3p mimic in vitro and agomir in vivo lowered the expression levels of MARCKS, thereby alleviating apoptosis and inflammation to relieve HI/R injury. Furthermore, miR-142- 3p inhibitor in vitro and antagomir in vivo up-regulated the expression levels of MARCKS to aggravate HI/R damage via promoting inflammation and apoptosis. Consistently, MARCKS siRNA markedly inhibited HI/R injury by restraining apoptosis and inflamm- ation in mice. MiR-142-3p played a considerable part in adjusting HI/R injury by targeting MARCKS, and miR-142-3p/MARCKS should be a new therapeutic target for HI/R injury.
Magnetic reconnection is important to the dynamics of many astrophysical and fusion plasmas but our understanding of it is incomplete. Petaflop-scale simulations of the evolution of turbulent ...magnetic reconnection in a three-dimensional plasma indicate that it proceeds in a way that is dramatically different from classical theory. PUBLICATION ABSTRACT
The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly ...upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.
To maintain the pressure of cargo tank and to minimize natural gas loss, two nitrogen expansion cycles for boil-off gas (BOG) re-liquefaction systems, specifically designed for small LNG ships are ...proposed and optimized: 1) Case 1, re-liquefaction process with the parallel nitrogen expansion, 2) Case 2, re-liquefaction process with the serial nitrogen expansion. The simulation and analysis of the two processes are carried out by using Aspen HYSYS and the genetic algorithms are selected as the optimization method. It can be found that the specific energy consumption (SEC) of 0.7333 kWh/kgLNG, the coefficient of performance (COP) of 0.2538 and the figure of merit (FOM) of 0.2827 are achieved in Case 1 and the SEC of 0.7539 kWh/kgLNG, the COP of 0.2464 and the FOM of 0.2757 are achieved in Case 2 by comparing the two optimized cases. Moreover, the total exergy losses for Case 1 and Case 2 are 153.34 kW and 160.69 kW, respectively.
•Two BOG re-liquefaction systems designed for small LNG ships are proposed.•Genetic algorithm is selected as the optimization method for the two processes.•The SEC, COP and FOM of the two proposed systems are compared and analyzed.•The proposed systems and other systems are compared and analyzed.
The heterogeneity of glioblastoma contributes to the poor and variant prognosis. The aim of this retrospective study was to assess the glioblastoma heterogeneity with MR imaging textures and to ...evaluate its impact on survival time.
A total of 133 patients with primary glioblastoma who underwent postcontrast T1-weighted imaging (acquired before treatment) and whose data were filed with the survival times were selected from the Cancer Genome Atlas. On the basis of overall survival, the patients were divided into 2 groups: long-term (≥12 months,
= 67) and short-term (<12 months,
= 66) survival. To measure heterogeneity, we extracted 3 types of textures, co-occurrence matrix, run-length matrix, and histogram, reflecting local, regional, and global spatial variations, respectively. Then the support vector machine classification was used to determine how different texture types perform in differentiating the 2 groups, both alone and in combination. Finally, a recursive feature-elimination method was used to find an optimal feature subset with the best differentiation performance.
When used alone, the co-occurrence matrix performed best, while all the features combined obtained the best survival stratification. According to feature selection and ranking, 43 top-ranked features were selected as the optimal subset. Among them, the top 10 features included 7 run-length matrix and 3 co-occurrence matrix features, in which all 6 regional run-length matrix features emphasizing high gray-levels ranked in the top 7.
The results suggest that local and regional heterogeneity may play an important role in the survival stratification of patients with glioblastoma.
This paper initiates the theoretical analysis of nonlinear microbeams and investigates the static bending, postbuckling and free vibration. The nonlinear model is conducted within the context of ...non-classical continuum mechanics, by introducing a material length scale parameter. The nonlinear equation of motion, in which the nonlinear term is associated with the mean axial extension of the beam, is derived by using a combination of the modified couple stress theory and Hamilton’s principle. Based on this newly developed model, calculations have been performed for microbeams simply supported between two immobile supports. The static deflections of a bending beam subjected to transverse force, the critical buckling loads and buckled configurations of an axially loaded beam, and the nonlinear frequencies of a beam with initial lateral displacement are discussed. It is shown that the size effect is significant when the ratio of characteristic thickness to internal material length scale parameter is approximately equal to one, but is diminishing with the increase of the ratio. Our results also indicate that the nonlinearity has a great effect on the static and dynamic behaviors of microscale beams. To attain accurate and reliable characterization of the static and dynamic properties of microscale beams, therefore, both the microstructure-dependent parameters and the nonlinearities have to be incorporated in the design of microscale beam devices and systems.
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