Search

Idarubicin (IDA), an anthracycline antineoplastic drug, is commonly used in the treatment of acute myeloid leukemia (AML) with reasonable response rates and clinical benefits. However, some patients still relapse, or do not respond, and suffer high fatality rates. Recent studies have shown that overexpression of PARP-1 may represent an important risk factor in AML patients. The aim of the present study was to determine the underlying molecular mechanisms by which the PARP-1 inhibitor Olaparib enhances the chemosensitivity of the leukemia cell line K562 and THP1 to IDA. Our data demonstrated that PARP-1 is upregulated in AML patients as well as in K562 and THP1 cells, and that the suppression of PARP-1 activity by Olaparib enhances the inhibitory effect of IDA. A mechanistic study revealed that Olaparib decreases the expressions of p-ATM, p-IκBα, XIAP and p65, and upregulates Bax, cleaved-Caspase-3 and γ-H2AX. Olaparib can enhance the induction of DNA damage by IDA, probably mediated by the inhibition of the ATM-related DNA damage response. Moreover, we also found that the nuclear translocation of p65 and the nuclear export of NEMO are inhibited when IDA and Olaparib are combined. Our results suggest that Olaparib attenuates the activity of the NF-κB pathway and decreases the DNA damage response induced by IDA. Therefore, we conclude that Olaparib is a potentially valuable chemosensitizer for leukemia patients.

Background: Numerous studies have manifested long noncoding RNAs (lncRNAs) as biomarkers to determine the prognosis of multiple myeloma (MM) patients. Nevertheless, the prognostic role of lncRNAs in MM is still ambiguous. Herein, we performed a meta‐analysis to evaluate the predictive value of aberrantly expressed lncRNAs in MM. Methods: A systemic literature search was performed in PubMed, EMBASE, Cochrane, and Web of Science databases until October 9, 2021, and the protocol was registered in the PROSPERO database (CRD42021284364). Our study extracted the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression‐free survival (PFS), or event‐free survival (EFS). Begg's and Egger's tests were employed to correct publication bias. Result: Twenty‐six individual studies containing 3501 MM patients were enrolled in this study. The results showed that aberrant expression of lncRNAs was associated with poor OS and PFS of MM patients. The pooled HRs for univariate OS and PFS were 1.48 (95% CI = 1.17–1.88, p < 0.001) and 1.30 (95% CI = 1.18‐1.43, p < 0.001), respectively, whereas the pooled HRs for multivariate OS and PFS were 1.50 (95% CI = 1.16‐1.95, p < 0.001) and 1.59 (95% CI = 1.22‐2.07, p < 0.001), respectively. Subgroup analysis suggested that MALAT1, TCF7, NEAT1, and PVT1 upregulation were associated with poor OS (p < 0.05), PVT1, and TCF7 upregulation were implicated with worse PFS (p < 0.05), while only TCF7 overexpression was correlated with reduced EFS (p < 0.05). Moreover, the contour‐enhanced funnel plot demonstrated the reliability of our current conclusion, which was not affected by publication bias. Conclusion: Aberrantly expressed particular lncRNAs are critical prognostic indicators in long‐term survival as well as promising biomarkers in progression‐free status. However, different cutoff values and dissimilar methods to assess lncRNA expression among studies may lead to heterogeneity. [ABSTRACT FROM AUTHOR]

The goal of this study is to investigate the spatiotemporal variation characteristics of LULC and to explore the impact of climate variability and LULC change on regional NPP in Jianghan Plain from 2000 to 2010 based on the CASA model, remote sensing data sets, meteorological data and LULC data. The results are summarized as follows: (1) the significant geographical variations are characterized mainly by the transformation from farmland to wetlands and constructive land. (2) The highest yield of NPP was 557.37 gC/m2 in 2007, and the lowest yield was 483.45 gC/m2 in 2009. (3) NPP spatial distribution has obvious uneven characteristics on the regional scale. (4) The correlation analysis shows that the correlation coefficient between annual total NPP and the annual precipitation and annual temperature was –0.4471 and 0.6296, respectively. Finally, the results may provide scientific information for investigating the influence of climate variability and LULC change on regional NPP in China. [ABSTRACT FROM AUTHOR]

Regarding the ever increasing and frequent occurrence of serious landslide disaster in eastern Guangxi, the current study were implemented to adopt support vector machines (SVM), particle swarm optimization support vector machines (PSO-SVM), random forest (RF), and particle swarm optimization random forest (PSO-RF) methods to assess landslide susceptibility by Zhaoping County. To this end, 10 landslide disaster-related causal variables including digital elevation model (DEM)-derived, meteorology-derived, Landsat8-derived, geology-derived, and human activities factors were selected for running four machine-learning (ML) methods, and landslide susceptibility evaluation maps were produced. Then, receiver operating characteristics (ROC) curves, and field investigation were performed to verify the efficiency of these models. Analysis and comparison of the results denoted that all four ML models performed well for the landslide susceptibility evaluation as indicated by the values of ROC curves – from 0.863 to 0.934. Moreover, the results also indicated that the PSO algorithm has a good effect on SVM and FR models. In addition, such a result also revealed that the PSO-RF and PSO-SVM models have the strong robustness and stable performance, and those two models are promising methods that could be transferred to other regions for landslide susceptibility evaluation. [ABSTRACT FROM AUTHOR]

Idarubicin (IDA), an anthracycline antineoplastic drug, is commonly used in the treatment of acute myeloid leukemia (AML) with reasonable response rates and clinical benefits. However, some patients still relapse, or do not respond, and suffer high fatality rates. Recent studies have shown that overexpression of PARP-1 may represent an important risk factor in AML patients. The aim of the present study was to determine the underlying molecular mechanisms by which the PARP-1 inhibitor Olaparib enhances the chemosensitivity of the leukemia cell line K562 and THP1 to IDA. Our data demonstrated that PARP-1 is upregulated in AML patients as well as in K562 and THP1 cells, and that the suppression of PARP-1 activity by Olaparib enhances the inhibitory effect of IDA. A mechanistic study revealed that Olaparib decreases the expressions of p-ATM, p-IκBα, XIAP and p65, and upregulates Bax, cleaved-Caspase-3 and γ-H2AX. Olaparib can enhance the induction of DNA damage by IDA, probably mediated by the inhibition of the ATM-related DNA damage response. Moreover, we also found that the nuclear translocation of p65 and the nuclear export of NEMO are inhibited when IDA and Olaparib are combined. Our results suggest that Olaparib attenuates the activity of the NF-κB pathway and decreases the DNA damage response induced by IDA. Therefore, we conclude that Olaparib is a potentially valuable chemosensitizer for leukemia patients.