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Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is the most abundant and expressed widely member of the hnRNP family. It has been extensively studied in developmental biology, oncology, and neurodegenerative diseases, which has not been reported on in intracerebral hemorrhage (ICH) induced-secondary brain injury (SBI). The purpose of this study was to explore the role of hnRNPA1 exerts and its underlying mechanism in ICH-induced SBI. Experimental ICH models were established by injecting autologous heart blood into the basal ganglia region of rats and increased or inhibited hnRNPA1 expression through the hnRNPA1 plasmid and small interfering RNA. The results illustrated that the protein levels of hnRNPA1 are significantly elevated after ICH, and hnRNPA1 is transported from the nucleus to the cytoplasm. Upregulated hnRNPA1 could improve neurological function and the learning and memory ability decline after ICH-induced injury. Furthermore, TUNEL and FJB staining indicated that hnRNPA1 overexpression could reduce neuronal cell death and injury induced by ICH. However, downregulated hnRNPA1 damages neurological function and learning and memory abilities and aggravates neuronal cell degeneration and apoptosis. Consistently, the levels of Bcl-xl mRNA and Bcl-xl are elevated or decreased depending on the levels of hnRNPA1, which could be one of the mechanisms through which hnRNPA1 participates in ICH-induced neuronal cell death. In summary, hnRNPA1 plays a protective role in ICH-induced SBI via upregulating Bcl-xl expression, indicating that hnRNPA1 could be a potential target for ICH therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

BACKGROUND Ubiquilin-4 (UBQLN4) is a component of the ubiquitin-proteasome system and regulates the degradation of many proteins implicated in pathological conditions. The aim of this study was to determine the role of UBQLN4 in regulating the proliferation and survival of the normal gastric epithelial cell line GES-1. MATERIAL AND METHODS We constructed GES-1 lines stably overexpressing UBQLN4 by lentiviral infection. Cell proliferation, apoptosis, and the cell cycle were analyzed using the MTT assay and flow cytometric assays. Phosphorylation of ERK, JNK, p38, and expression of cyclin D1 were detected by western blot analysis. RESULTS Overexpression of UBQLN4 significantly reduced proliferation and induced G2/M phase arrest and apoptosis in GES-1 cells. Moreover, upregulation of UBQLN4 increased the expression of cyclin D1 and phosphorylated ERK, but not JNK or p38. CONCLUSIONS These data suggest that UBQLN4 may induce cell cycle arrest and apoptosis via activation of the ERK pathway and upregulation of cyclin D1 in GES-1 cells.

Taspine is an active compound in anticancer agent development. 12k was synthesized with taspine as lead compound bearing biphenyl scaffold and showed potent anticancer activity. Here, we investigated the effect of taspine derivative 12k on A549 lung cells. We showed that 12k not only decreased significantly A549 cell viability, A549 cell colony formation but also impaired A549 cell migration. Moreover, 12k treatment blocked cell cycle progression by increasing cell number in S phase to 42.80% for 6 μmol/L vs. 28.86% for control while decreasing cell number in G1 phase. Accordingly, this was associated with an increase protein expression of cyclin E and a decrease protein expression of cyclin D1, cyclin B1 and its associated CDK1 (cdc2). Meanwhile, we found that 12k induced A549 cell apoptosis, which was closely associated with the effect of the Bcl-2 family. Increase of Bad, Bak and Bax expression levels, decrease of Bcl-2 and Mcl-1 expression levels were observed. SiRNA knockdown of c-myc in A549 cells significantly attenuated tumor inhibition effects of 12k. In conclusion, our results demonstrate that 12k has an inhibitory effect on growth of A549 cell by inducing cell cycle arrest and apoptosis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Liver dysfunction has been known to occur frequently in cases of sepsis. Baicalein, the main active ingredient of the Scutellaria root, exerts anti-inflammatory and anti-apoptotic properties in endotoxic shock. However, the role of baicalein in polymicrobial sepsis-induced liver injury and its regulatory mechanisms remain unclear. In this study, we aimed to investigate the protective effects of baicalein on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were treated with baicalein (100mg/kg, i.p) at 1h, 6h and 12h following CLP. Baicalein significantly improved the survival of septic mice. Treatment with baicalein ameliorated the CLP-induced liver injury, as indicated by the lower serum aminotransferase levels and the fewer histopathologic abnormalities. Baicalein reduced the neutrophil infiltration and the hepatic inflammatory cytokine expression and release. It also decreased the hepatic and the serum high-mobility group box 1 and macrophage migration inhibitory factor levels in septic mice. Moreover, baicalein significantly inhibited the mitogen-activated protein kinases (MAPKs) activation and suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB). In conclusion, these results suggest that baicalein treatment could protect against the sepsis-induced liver injury, and improve the survival of mice with polymicrobial sepsis. The mechanism of the protective action of baicalein seems to involve its ability to reduce inflammatory response, to inhibit hepatic apoptosis, and to suppress MAPKs and NF-κB activation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK-) 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP), and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB) but enhanced the transcriptional activity of cAMP response element binding protein (CREB) in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyeloma activity by inhibiting histone deacetylases (HDACs). Amitriptyline markedly decreased cyclin D2 promoter-driven luciferase activity, reduced cyclin D2 expression, and arrested cells at the G(0)/G(1) phase of the cell cycle. Amitriptyline-induced apoptosis was confirmed by Annexin V staining, and cleavage of caspase-3 and poly(ADP-ribose) polymerase-1. D-Cyclin expression is reported to be epigenetically regulated by histone acetylation. Thus, we examined the effects of amitriptyline on histone 3 (H3) acetylation and demonstrated that amitriptyline increased acetylation of H3 and expression of p27 and p21. Further studies indicated that amitriptyline interfered with HDAC function by down-regulation of HDAC3, -6, -7, and -8, but not HDAC2, and by interacting with HDAC7. Molecular docking analysis and molecular dynamics simulations revealed that amitriptyline bound to HDAC7 and formed strong van der Waals interactions with five residues of HDAC7, including Phe162, His192, Phe221, Leu293, and His326, thus inhibiting HDAC activity. Therefore, we found that amitriptyline inhibited cyclin D2 transactivation and HDAC activity and could be a promising treatment for multiple myeloma.

The article titled "Two Mixed-Ligand Co(II)-Based Coordination Polymers: Treatment Activity on Pediatric Asthma Via Inducing Eosinophil Apoptosis through Down-Regulating Bcl-2 Expression" has been retracted by the Editor-in-Chief and the Publisher of the Journal of Cluster Science. The retraction was prompted by evidence of systematic manipulation of the publication process, including citations that do not support claims made in the text, non-standard phrasing, anomalies in the figures, and discrepancies in ethics approval statements. The authors have not responded to correspondence regarding the retraction. Springer Nature, the publisher, remains neutral in regards to jurisdictional claims and institutional affiliations. [Extracted from the article]

In this work, two coordination polymers containing Co(II) ions as nodes, namely, [Co(NDC)(L)(H2O)]n (1, H2NDC = 1,4-naphthalene dicarboxylic acid) and [Co(DCTP)(L)·(H2O)2]n (2, H2DCTP = 2,5-dichloroterephthalic acid) were prepared based on 1,4-bis(5,6-dimethylbenzimidazole)butane (L), the flexible N-donor ligand and different dicarboxylate ligand. Their treatment activity on the pediatric asthma was evaluated in the biological research. Firstly, the enzyme linked immunosorbent assay (ELISA) detection was carried out to determine the IL-1β and TNF-α content in the bronchus. The inflammatory response in the bronchial epithelial cells was determined by the real time reverse transcription-polymerase chain reaction (RT-PCR). After that, the eosinophil apoptosis in the airway was measured. Finally, the western was performed for the confirmation of eosinophil apoptosis by detecting Bcl-2 and caspase-3. [ABSTRACT FROM AUTHOR]

Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPARγ expression and its activity. Moreover, inactivation of PPARγ by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation and apoptosis. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPARγ leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell. [ABSTRACT FROM AUTHOR]

Background and objective: Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. Study design and methods: A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1β, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins. Results: A549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1β, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC. Conclusion: Our research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways: 1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) patients have an estimated survival of ~15 months with treatment, and the standard of care only modestly enhances patient survival. Identifying biomarkers representing vulnerabilities may allow for the selection of efficacious chemotherapy options to address personalized variations in GBM tumors. Irinotecan targets topoisomerase I (TOP1) by forming a ternary DNA–TOP1 cleavage complex (TOP1cc), inducing apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that may reduce the effectiveness of irinotecan. We treated GBM cell lines with increasing concentrations of irinotecan and compared the IC50 values. We found that the TDP1/TOP1 activity ratio had the strongest correlation (Pearson correlation coefficient R = 0.972, based on the average from three sets of experiments) with IC50 values following irinotecan treatment. Increasing the TDP1/TOP1 activity ratio by the ectopic expression of wild-type TDP1 increased in irinotecan IC50, while the expression of the TDP1 catalytic-null mutant did not alter the susceptibility to irinotecan. The TDP1/TOP1 activity ratio may be a new predictive indicator for GBM vulnerability to irinotecan, allowing for the selection of individual patients for irinotecan treatment based on risk–benefit. Moreover, TDP1 inhibitors may be a novel combination treatment with irinotecan to improve GBM patient responsiveness to genotoxic chemotherapies. [ABSTRACT FROM AUTHOR]

Background: The JAK2-STAT signaling pathway plays a critical role in myeloproliferative neoplasms (MPN). An activating mutation in JAK2 (V617F) is present in ~ 95% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis cases. This study aims to explore the selective JAK2V617F inhibitor, evaluate the efficacy and possible mechanism of ZT55 on MPN. Methods: HTRF assays were conducted to evaluate the selective inhibition of ZT55 for JAKs. Cell apoptosis, proliferation, and cycle arrest assays were performed to examine the effect of ZT55 on HEL cell line with JAK2V617F mutation in vitro. Western analysis was used to monitor the expression and activity of proteins on JAK2/STAT pathway. A mice xenograft model was established to evaluate the antitumor efficacy of ZT55 in vivo. Peripheral blood samples from patients with the JAK2V617F mutation were collected to estimate the effect of ZT55 on erythroid colony formation by colony-forming assay. Results: We found that ZT55 showed a selective inhibition of a 0.031 μM IC50 value against JAK2. It exhibited potent effects on the cellular JAK-STAT pathway, inhibiting tyrosine phosphorylation in JAK2V617F and downstream STAT3/5 transcription factors. ZT55 inhibited the proliferation of the JAK2V617F-expressing HEL cell line, leading to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis. Notably, ZT55 also significantly suppressed the growth of HEL xenograft tumors in vivo. Further evaluation indicated that ZT55 blocked erythroid colony formation of peripheral blood hematopoietic progenitors from patients carrying the JAK2V617F mutation. Conclusion: These results suggest that ZT55 is a highly-selective JAK2 inhibitor that can induce apoptosis of human erythroleukemia cells by inhibiting the JAK2-STAT signaling. [ABSTRACT FROM AUTHOR]