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Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods: First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results: AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion: Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a common cerebrovascular disease with high morbidity, disability, and mortality worldwide. Currently, recombinant tissue plasminogen activator is the main intravenous thrombolysis agent for the treatment of acute ischemic stroke within 4.5 h after onset. Hemorrhagic transformation (HT) is the most serious complication of intravenous thrombolysis, which can significantly aggravate clinical poor prognosis. Therefore, it is important to early predict the risk of post-thrombolysis HT in patients with acute ischemic stroke. Summary: Recently, several studies have reported that neuroimaging techniques have potential value in predicting HT after intravenous thrombolysis in patients with acute ischemic stroke. The corresponding neuroimaging parameters may be effective predictors of HT after intravenous thrombolysis. In this review, we summarized and discussed the application of neuroimaging techniques and related parameters in predicting HT after intravenous thrombolysis. Key Messages: Recognizing and understanding the predictive performance of neuroimaging parameters for HT may help assess the risk of HT after intravenous thrombolysis in patients with acute ischemic stroke and make an appropriate treatment decision. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations exhibits distinct biological and clinical features, accounting for approximately one-third of AML. Recently, the N 6-methyladenosine (m6A) RNA modification has emerged as a new epigenetic modification to contribute to tumorigenesis and development. However, there is limited knowledge on the role of m6A modifications in NPM1-mutated AML. In this study, the decreased m6A level was first detected and high expression of fat mass and obesity-associated protein (FTO) was responsible for the m6A suppression in NPM1-mutated AML. FTO upregulation was partially induced by NPM1 mutation type A (NPM1-mA) through impeding the proteasome pathway. Importantly, FTO promoted leukemic cell survival by facilitating cell cycle and inhibiting cell apoptosis. Mechanistic investigations demonstrated that FTO depended on its m6A RNA demethylase activity to activate PDGFRB/ERK signaling axis. Our findings indicate that FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated AML and provide a new layer of epigenetic insight for future treatments of this distinctly leukemic entity. [ABSTRACT FROM AUTHOR]

As a new mechanism of enhancing oil recovery by low-salinity water-flooding, osmotic pressure has been widely studied in recent years. The injected water molecules enter the original formation water-drops wrapped by oil droplets under osmotic pressure, resulting in apparent expansion of crude oil. However, at present, the effect of osmotic pressure alone on crude oil droplets expansion is not obvious, and the research is only limited to qualitative research, lacking quantitative analysis. In this study, three kinds of nano silica are used as an oil droplet expansion displacement agents, and the water in oil ( W/0) emulsion is used to simulate the original oil-water distribution in the reservoir to observe the expansion effect of W/O emulsion droplets and quantitatively calculate droplets' expansion ratio. The experimental results show that both hydrophilic and hydrophobic nano silica can enhance the expansion ratio of oil droplets, and the expansion ratio by hydrophilic HS-40 nano silica is higher than that by other two kinds of nano silica because of its smaller particle size and higher absolute zeta potential. With the increase of HS-40 concentration, the surfactant molecules at the oil-water interface enter the oil droplets and accelerate the expansion of the droplets. The maximum expansion ratio reaches 3. 29 when the concentration of HS-40 is 0. 20%. With the continual increase of HS-40 concentration, nano silica particles will hinder the transfer of water molecules at the oil-water interface into the droplets. On the condition that there are large salinity differences between formation water and injection water, the existence of nano silica can accelerate the expansion of oil droplets, which provides a new way for low-salinity waterflooding. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and the risk of ischaemic stroke and carotid atherosclerosis in adults. Methods: We systematically searched PubMed, EMBASE, Web of Science and other databases for relevant studies on serum ADMA and ischaemic stroke or carotid atherosclerosis, which were published from December 1980 to December 2019. The quality of the included studies was evaluated according to the Cochrane system evaluation standard. The difference in serum ADMA level between ischaemic stroke and control group was selected as the effect size (standardized mean difference, SMD). The pooled analysis was performed using Review Manager (V.5.3). Results: According to the selection criteria, thirteen studies were included in the meta‐analysis after screening. Nine studies compared ADMA levels between the ischaemic stroke group and healthy control group, involving a total of 1315 and 880 subjects in the two groups, respectively. Pooled effect sizes were calculated using the random‐effects model due to the high heterogeneity (I2 = 93%, P <.00001). The level of serum ADMA in patients with ischaemic stroke was significantly higher than that in healthy people (SDM = 0.69, 95% CI [0.32, 1.06], P =.0002). Seven of the thirteen articles compared ADMA levels between the carotid arteriosclerosis group and the healthy control group, with 559 and 330 subjects in the two groups, respectively. The random‐effects model was applied due to the high heterogeneity (I2 = 91%, P <.00001). The level of serum ADMA in patients with carotid arteriosclerosis was significantly higher than that in healthy people (SDM = 1.03, 95% CI [0.49, 1.57], P =.0002). Conclusion: The serum ADMA may be related to ischaemic stroke, and it is a risk factor for carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Granulosa cells are somatic cells located inside follicles that play a crucial role in the growth and development of follicles. Quercetin and tanshinone are two key monomers in traditional Chinese medicine that have antioxidant and anti-aging properties. The KGN cell apoptosis model caused by triptolide (TP) was employed in this work to investigate granulosa cell death and medication rescue. Quercetin and tanshinone therapy suppressed KGN cell death and oxidation while also regulating the expression of critical apoptosis and oxidation-related markers such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Further research revealed that the effects of Quercetin and Tanshinone were accomplished via deacetylation of FOXO3A in the cytoplasm and mitochondria via the SIRT1/SIRT3-FOXO3a axis. In summary, Quercetin and tanshinone protect KGN cells from apoptosis by reducing mitochondrial apoptosis and oxidation via the SIRT1/SIRT3-FOXO3a axis.

The placenta plays a pivotal role in the maintenance of normal pregnancy, but how it forms, matures, and performs its function remains poorly understood. Here, we describe a novel mouse line (Prl3d1-iCre) that expresses iCre recombinase under the control of the endogenous prl3d1 promoter. Prl3d1 has been proposed as a marker for distinguishing trophoblast giant cells (TGCs) from other trophoblast cells in the placenta. The in vivo efficiency and specificity of the Cre line were analyzed by interbreeding Prl3d1-iCre mice with B6-G/R reporter mice. Through anatomical studies of the placenta and other tissues of Prl3d1-iCre/+; B6-G/R mouse mice, we found that the tdTomato signal was expressed in parietal trophoblast giant cells (P-TGCs). Thus, we report a mouse line with ectopic Cre expression in P-TGCs, which provides a valuable tool for studying human pathological pregnancies caused by implantation failure or abnormal trophoblast secretion due to aberrant gene regulation., (© 2023 Wiley Periodicals LLC.)

Acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations exhibits distinct biological and clinical features, accounting for approximately one-third of AML. Recently, the N 6 -methyladenosine (m 6 A) RNA modification has emerged as a new epigenetic modification to contribute to tumorigenesis and development. However, there is limited knowledge on the role of m 6 A modifications in NPM1-mutated AML. In this study, the decreased m 6 A level was first detected and high expression of fat mass and obesity-associated protein (FTO) was responsible for the m 6 A suppression in NPM1-mutated AML. FTO upregulation was partially induced by NPM1 mutation type A (NPM1-mA) through impeding the proteasome pathway. Importantly, FTO promoted leukemic cell survival by facilitating cell cycle and inhibiting cell apoptosis. Mechanistic investigations demonstrated that FTO depended on its m 6 A RNA demethylase activity to activate PDGFRB/ERK signaling axis. Our findings indicate that FTO-mediated m 6 A demethylation plays an oncogenic role in NPM1-mutated AML and provide a new layer of epigenetic insight for future treatments of this distinctly leukemic entity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Lei, Ren, Peng, Jing, Jiang, Huang, Tao, Lin, Yang, Sun, Tang, Wei, Yang and Zhang.)