Thermochromic Vanadium Dioxide Nanostructures for Smart Windows and Radiative Cooling.

The pursuit of energy-saving materials and technologies has garnered significant attention for their pivotal role in mitigating both energy consumption and carbon emissions. In particular, thermochromic windows in buildings offer energy-saving potential by adjusting the transmittance of solar irradiation in response to temperature changes. Radiative cooling (RC), radiating thermal heat from an object surface to the cold outer space, also offers a potential way for cooling without energy consumption. Accordingly, smart window and RC technologies based on thermochromic materials can play a crucial role in improving energy efficiency and reducing energy consumption in buildings in response to the surrounding temperature. Vanadium dioxide (VO2) is a promising thermochromic material for energy-saving smart windows and RC due to its reversible metal-to-insulator transition, accompanying large changes in its optical properties. This review provides a brief summary of synthesis methods of VO2 nanostructures based on nanoparticles and thin films. Moreover, this review emphasizes and summarizes modulation strategies focusing on doping, thermal processing, and structure manipulation to improve and regulate the thermochromic and emissivity performance of VO2 for smart window and RC applications. In last, the challenges and recent advances of VO2-based smart window and RC applications are briefly presented.

Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.

Checkpoint kinase 1 (Chk1) is a key mediator of the DNA damage response that regulates cell cycle progression, DNA damage repair, and DNA replication. Small-molecule Chk1 inhibitors sensitize cancer cells to genotoxic agents and have shown preclinical activity as single agents in cancers characterized by high levels of replication stress. However, the underlying genetic determinants of Chk1-inhibitor sensitivity remain unclear. Although treatment options for advanced colorectal cancer are limited, radiotherapy is effective. Here, we report that exposure to a novel amidine derivative, K1586, leads to an initial reduction in the proliferative potential of colorectal cancer cells. Cell cycle analysis revealed that the length of the G2/M phase increased with K1586 exposure as a result of Chk1 instability. Exposure to K1586 enhanced the degradation of Chk1 in a time- and dose-dependent manner, increasing replication stress and sensitizing colorectal cancer cells to radiation. Taken together, the results suggest that a novel amidine derivative may have potential as a radiotherapy-sensitization agent that targets Chk1.

IGFL2-AS1, a Long Non-Coding RNA, Is Associated with Radioresistance in Colorectal Cancer.

Precise prediction of radioresistance is an important factor in the treatment of colorectal cancer (CRC). To discover genes that regulate the radioresistance of CRCs, we analyzed an RNA sequencing dataset of patient-originated samples. Among various candidates, IGFL2-AS1, a long non-coding RNA (lncRNA), exhibited an expression pattern that was well correlated with radioresistance. IGFL2-AS1 is known to be highly expressed in various cancers and functions as a competing endogenous RNA. To further investigate the role of IGFL2-AS1 in radioresistance, which has not yet been studied, we assessed the amount of IGFL2-AS1 transcripts in CRC cell lines with varying degrees of radioresistance. This analysis showed that the more radioresistant the cell line, the higher the level of IGFL2-AS1 transcripts-a similar trend was observed in CRC samples. To directly assess the relationship between IGFL2-AS1 and radioresistance, we generated a CRC cell line stably expressing a small hairpin RNA (shRNA) targeting IGFL2-AS1. shRNA-mediated knockdown of IGFL2-AS1 decreased radioresistance and cell migration in vitro, establishing a functional role for IGFL2-AS1 in radioresistance. We also showed that downstream effectors of the AKT pathway played crucial roles. These data suggest that IGFL2-AS1 contributes to the acquisition of radioresistance by regulating the AKT pathway.

Hyperacetylation of the C-terminal domain of p53 inhibits the formation of the p53/p21 complex.

Given our previous finding that certain tumor-suppressing functions of p53 are exerted by the p53/p21 complex, rather than p53 alone, cells may have a system to regulate the p53/p21 interaction. As p53 binds to p21 via its C-terminal domain, which contains acetylable lysine residues, we investigated whether the C-terminal acetylation of p53 influences the p53/p21 interaction. Indeed, the p53/p21 interaction was reduced when various types of cells (HCT116 colon cancer, A549 lung cancer, and MCF7 breast cancer cells) were treated with MS-275, an inhibitor of SIRT1 (a p53 deacetylase), or with SIRT1-targeting small interfering RNAs. These treatments also increased the acetylation levels of the five lysine residues (K370, K372, K373, K381, K382) in the C-terminal domain of p53. The p53/p21 interaction was also reduced when these lysine residues were substituted with glutamine (an acetylation memetic), but not arginine (an unacetylable lysine analog). While the inhibitory effect of the lysine-to-glutamine substitution was evident upon the substitution of all the five lysine residues, the substitution of only two (K381, K382) or three residues (K370, K372, K373) was less effective. Consistently, the five substitutions reduced the ability of p53 to regulate cell invasion and death by liberating Bax from Bcl-w. Overall, our data suggest that the acetylation, especially the hyperacetylation, of the p53 C-terminal domain suppresses the p53/p21-complex-dependent functions of p53 by inhibiting the p53/p21 interaction. We propose that cellular components involved in the acetylation or deacetylation of the p53 C-terminus are critical regulators of the formation of p53/p21 complex.

Involvement of the p53/p21 complex in p53-dependent gene expression.

The p53 tumor suppressor regulates cell functions either by acting as a transcription factor or by interacting with other proteins. Previously, we reported that the non-transcriptional actions of p53 can be facilitated by the binding of p53 to p21. Herein, we investigated whether p53/p21 interaction influences the transcriptional activity of p53. We observed that the expression of the p53 promoter-based reporter gene is dependent on p21 levels. Moreover, using a p21 variant that is unable to bind p53, we showed that p53 promoter activity requires p53/p21 interaction. To investigate the possible role of p21 in regulating the expression of endogenous p53 targets, we analyzed mRNA levels of Puma, Mdm2, and Gadd45a in untreated control and γ-ray-irradiated cells. We observed that while Puma expression is dependent on p53 regardless of γ-irradiation, p53 mediates the expression of Mdm2 and Gadd45a only in irradiated cells. Notably, p53/p21 interaction is required only for the p53-dependent expression of the tested genes and not Mdm2 and Gadd45a in non-irradiated cells. Moreover, chromatin immunoprecipitation assay revealed that p21 is required for the binding of p53 to the promoters of Puma, Mdm2, and Gadd45a. Collectively, our data support the view that the p53/p21 complex is involved in regulating p53-dependent gene expression. These findings provide a new foundation for understanding the transcriptional action of p53.

Low-Dose Radiation Affects Cardiovascular Disease Risk in Human Aortic Endothelial Cells by Altering Gene Expression under Normal and Diabetic Conditions.

High doses of ionizing radiation can cause cardiovascular diseases (CVDs); however, the effects of <100 mGy radiation on CVD remain underreported. Endothelial cells (ECs) play major roles in cardiovascular health and disease, and their function is reduced by stimuli such as chronic disease, metabolic disorders, and smoking. However, whether exposure to low-dose radiation results in the disruption of similar molecular mechanisms in ECs under diabetic and non-diabetic states remains largely unknown; we aimed to address this gap in knowledge through the molecular and functional characterization of primary human aortic endothelial cells (HAECs) derived from patients with type 2 diabetes (T2D-HAECs) and normal HAECs in response to low-dose radiation. To address these limitations, we performed RNA sequencing on HAECs and T2D-HAECs following exposure to 100 mGy of ionizing radiation and examined the transcriptome changes associated with the low-dose radiation. Compared with that in the non-irradiation group, low-dose irradiation induced 243 differentially expressed genes (DEGs) (133 down-regulated and 110 up-regulated) in HAECs and 378 DEGs (195 down-regulated and 183 up-regulated) in T2D-HAECs. We also discovered a significant association between the DEGs and the interferon (IFN)-I signaling pathway, which is associated with CVD by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein−protein network analysis, and module analysis. Our findings demonstrate the potential impact of low-dose radiation on EC functions that are related to the risk of CVD.

Induction of interleukin-1 beta (IL-1ß) is a critical component of lung inflammation during influenza A (H1N1) virus infection.

Cytokine storm during influenza virus infection is recognized as a predictor of morbidity and mortality. To verify the cellular effects of influenza-induced cytokines in primary normal lung cells, human pulmonary microvascular endothelial cells (HMVECs) and lung fibroblast cells (MRC-5 cells) were infected with influenza virus H1N1. H1N1 infection induced the transcription of various genes encoding cytokines and chemokines such as interleukin-1 beta (IL-1ß), IL-6, IL-8, IL-12A, tumor necrosis factor alpha (TNF-α), and chemokine (C-C motif) ligand 5 (CCL5) in both endothelial cells and lung fibroblasts. Among them, IL-1ß induction by influenza infection increased the inflammation of lung cells; conversely, blockade of IL-1ß signals with an IL-1ß receptor antagonist or a neutralizing antibody alleviated influenza-driven inflammation. In conclusion, these data suggest that secreted IL-1ß by the endothelial cells contributes to influenza-induced inflammation, and blockade of IL-1ß signals is a potential treatment or therapeutic target for influenza-induced inflammation.

Microwave Sintering of Silver Nanoink for Radio Frequency Applications.

Microwave sintering is a promising method for low-temperature processes, as it provides advantages such as uniform, fast, and volumetric heating. In this study, we investigated the electrical characteristics of inkjet-printed silver (Ag) circuits sintered by microwaves. The microstructural evolutions of inkjet-printed Ag circuits sintered at various temperatures for different durations were observed with a field emission scanning electron microscope. The electrical properties of the inkjet-printed Ag circuits were analysed by electrical resistivity measurements and radio frequency properties including scattering-parameters in the frequency range of 20 MHz to 20 GHz. The experimental results show that the signal losses of the Ag circuits sintered by microwave heating were lower than those sintered by conventional heating as microwave heating led to granular films which were nearly fully sintered without pores on the surfaces. When the inkjet-printed Ag circuits were sintered by microwaves at 300 °C for 4 min, their electrical resistivity was 5.1 µΩ cm, which is 3.2 times larger than that of bulk Ag. Furthermore, microwave sintering at 150 °C for 4 min achieved much lower signal losses (1.1 dB at 20 GHz) than conventional sintering under the same conditions.

Inhibition of DAPK3 Suppresses Radiation-Induced Cellular Senescence by Activation of a PGC1α-Dependent Metabolism Pathway in Brain Endothelial Cells.

In the brain, environmental changes, such as neuroinflammation, can induce senescence, characterized by the decreased proliferation of neurons and dendrites and synaptic and vascular damage, resulting in cognitive decline. Senescence promotes neuroinflammatory disorders by senescence-associated secretory phenotypes and reactive oxygen species. In human brain microvascular endothelial cells (HBMVECs), we demonstrate that chronological aging and irradiation increase death-associated protein kinase 3 (DAPK3) expression. To confirm the role of DAPK3 in HBMVEC senescence, we disrupted DAPK3 activity using small interfering RNA (siRNA) or a dominant-negative mutant (DAPK3-P216S), which reduced cellular senescence phenotypes, as assessed by changes in tube formation, senescence-associated beta-galactosidase activity, and cell proliferation. In endothelial cells, DAPK3 promotes cellular senescence by regulating the phosphorylation and inactivation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) via the protein kinase B pathway, resulting in the decreased expression of mitochondrial metabolism-associated genes, such as ATP5G1, BDNF, and COX5A. Our studies show that DAPK3 is involved in cellular senescence and PGC1α regulation, suggesting that DAPK3 regulation may be important for treating aging-related brain diseases or the response to radiation therapy.

Characterization of Ag-Pd nanocomposite paste for electrochemical migration resistance.

Direct printing such as inkjet, gravure, and screen printing is an attractive approach for achieving low-cost circuitry in the printed circuit board industry. One of the challenges for direct printing technology, however, is the poor resistance to electrochemical migration (ECM), especially for silver (Ag) which has been widely used in printed electronics. We demonstrate improved resistance to Ag electrochemical migration by adding palladium (Pd) nanoparticles to the Ag nanopaste. Conductive comb-type patterns were fabricated on a bismaleimide-triazine substrate via screen printing. Their ECM characteristics were assessed by water drop test with deionized water. These results showed that the ECM time required for dendritic growth from cathode to anode to cause short-circuit failure was affected by the Pd content and applied voltages: the ECM time of Ag-15wt.% Pd nanopaste was nearly threefold that of Ag nanopaste, and the ECM time decreased by 94.22%, on average, while the applied voltage increased from 3 V to 9 V.

Deep Neural Network-Based Automatic Dicentric Chromosome Detection Using a Model Pretrained on Common Objects.

Dicentric chromosome assay (DCA) is one of the cytogenetic dosimetry methods where the absorbed dose is estimated by counting the number of dicentric chromosomes, which is a major radiation-induced change in DNA. However, DCA is a time-consuming task and requires technical expertise. In this study, a neural network was applied for automating the DCA. We used YOLOv5, a one-stage detection algorithm, to mitigate these limitations by automating the estimation of the number of dicentric chromosomes in chromosome metaphase images. YOLOv5 was pretrained on common object datasets. For training, 887 augmented chromosome images were used. We evaluated the model using validation and test datasets with 380 and 300 images, respectively. With pretrained parameters, the trained model detected chromosomes in the images with a maximum F1 score of 0.94 and a mean average precision (mAP) of 0.961. Conversely, when the model was randomly initialized, the training performance decreased, with a maximum F1 score and mAP of 0.82 and 0.873%, respectively. These results confirm that the model could effectively detect dicentric chromosomes in an image. Consequently, automatic DCA is expected to be conducted based on deep learning for object detection, requiring a relatively small amount of chromosome data for training using the pretrained network.

Neuromedin U contributes to radiation resistance in colorectal cancer via YAP/TAZ signaling activation.

Resistance to radiation therapy remains a treatment obstacle for patients with high­risk colorectal cancer. Neuromedin U (NMU) has been identified as a potential predictor of the response to radiation therapy by RNA sequencing analysis of colorectal cancer tissues obtained from patients. However, the role of NMU in colorectal cancer remains unknown. In order to investigate role of NMU in colorectal cancer, NMU expression was regulated using small interfering RNA or an NMU­expression pCMV3 vector, and cell counting, wound­healing and clonogenic assays were subsequently performed. NMU knockdown decreased colorectal cancer cell proliferation and migration, and sensitized the cells to radiation. Conversely, NMU overexpression increased radiation resistance, proliferation and migration of colorectal cancer cells. Furthermore, by western blotting and nuclear fractionation experiments, NMU knockdown inhibited the nuclear translocation of yes­associated protein (YAP) and transcriptional co­activator with PDZ­binding motif (TAZ), resulting from the phosphorylation of these proteins. By contrast, the nuclear translocation of YAP and TAZ was increased following NMU overexpression in colorectal cancer cells. Recombinant NMU regulated YAP and TAZ activity, and the expression of the YAP and TAZ transcriptional target genes AXL, connective tissue growth factor and cysteine­rich angiogenic inducer 61 in an NMU receptor 1 activity­dependent manner. These results suggested that NMU may contribute to the acquisition of radioresistance in colorectal cancer by enhancing the Hippo signaling pathway via YAP and TAZ activation.

Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors.

BACKGROUND/AIM: The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. MATERIALS AND METHODS: Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. RESULTS: Nebivolol, a third generation ß1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. CONCLUSION: Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

Adhesion characteristics of silver tracks screen-printed on polyimide with an environmental reliability test.

Printable and flexible electronics are increasingly being used in numerous applications that are miniaturized, multi-functional and lightweight. Simultaneously, reliability issues of the printed and flexible electronic devices are getting more attention. The adhesion of screen-printed silver (Ag) tracks on a polyimide (PI) film was investigated after two kinds of the environmental reliability test: a constant-temperature storage test, and a steady-state temperature and humidity storage test. Atmospheric-pressure plasma (APP) was adopted on the PI film surface to improve the poor adhesion derived from the inherent hydrophobicity. The Ag tracks constructed via screen printing were sintered at 250 degrees C for 30 min in air using a box-type muffle furnace. Some samples were exposed under 85 degrees C and 85% relative humidity (RH) for various durations (24, 72, 168 and 500 h), and others were aged at 85 degrees C with same durations to compare the influence of moisture on the adhesion. The adhesion of the screen-printed Ag tracks was evaluated by a roll-type 90 degrees peel test. The peel strength of the screen-printed Ag tracks decreased by 76.74% and 69.88% after 500 h run of the 85 degrees C/85% RH test, and the aging test, respectively. The weakest adhesion was 4.98 gf/mm after the 500 h run of the 85 degrees C/85% RH test. To demonstrate these experimental results, the microstructural evolution and chemical bonding states of the interfacial surfaces were characterized using a field emission scanning electron microscope (FE-SEM), and X-ray photoelectron spectroscope (XPS), respectively.

Electrochemical migration characteristics of screen-printed silver patterns on FR-4 substrate.

We evaluated the electrical reliability of screen-printed silver (Ag) patterns sintered at various temperatures under variable bias voltages. Comb-type patterns were screen-printed onto a flame resistance-4 substrate using a commercial Ag nanopaste (24 nm in diameter, 73 wt% of Ag nanoparticles). The printed patterns were then sintered for 30 min in air at various temperatures ranging from 100 degrees C to 200 degrees C. The microstructures and thickness profiles of the sintered conductive patterns were identified with a field emission scanning electron microscope and a 3-D surface profiler, respectively. In this study, the phenomenon of electrochemical migration was investigated with a water drop test with deionized water. These results showed that the time required by dendrites to bridge from a cathode to an anode was affected by the sintering temperature and applied voltage; when the sintering temperature was 200 degrees C, the time to achieve a short circuit was nearly four times that of the sample sintered at 100 degrees C, and while the applied voltage increased from 3 V to 9 V, the time to reach a short circuit decreased, on average, by 11%.

Ionizing Radiation-Induced GDF15 Promotes Angiogenesis in Human Glioblastoma Models by Promoting VEGFA Expression Through p-MAPK1/SP1 Signaling.

Glioblastoma multiforme (GBM), the most aggressive cancer type that has a poor prognosis, is characterized by enhanced and aberrant angiogenesis. In addition to surgical resection and chemotherapy, radiotherapy is commonly used to treat GBM. However, radiation-induced angiogenesis in GBM remains unexplored. This study examined the role of radiation-induced growth/differentiation factor-15 (GDF15) in regulating tumor angiogenesis by promoting intercellular cross-talk between brain endothelial cells (ECs) and glioblastoma cells. Radiation promoted GDF15 secretion from human brain microvascular endothelial cells (HBMVECs). Subsequently, GDF15 activated the transcriptional promoter VEGFA in the human glioblastoma cell line U373 through p-MAPK1/SP1 signaling. Upregulation of vascular endothelial growth factor (VEGF) expression in U373 cells resulted in the activation of angiogenic activity in HBMVECs via KDR phosphorylation. Wound healing, tube formation, and invasion assay results revealed that the conditioned medium of recombinant human GDF15 (rhGDF15)-stimulated U373 cell cultures promoted the angiogenic activity of HBMVECs. In the HBMVEC-U373 cell co-culture, GDF15 knockdown mitigated radiation-induced VEGFA upregulation in U373 cells and enhanced angiogenic activity of HBMVECs. Moreover, injecting rhGDF15-stimulated U373 cells into orthotopic brain tumors in mice promoted angiogenesis in the tumors. Thus, radiation-induced GDF15 is essential for the cross-talk between ECs and GBM cells and promotes angiogenesis. These findings indicate that GDF15 is a putative therapeutic target for patients with GBM undergoing radio-chemotherapy.

Regeneration of interfacial bonding force of waste carbon fibers by light: Process demonstration and atomic level analysis.

Although interest in recycling carbon fibers is rapidly growing, practical applications of recycled carbon fibers (rCFs) are limited owing to their poor wettability and adhesion. Surface modification of CFs was achieved through intense pulsed light (IPL) irradiation, which functionalizes surface of rCFs. Surface energy, chemical composition, morphology, and interfacial shear strength (IFSS) of rCFs before and after IPL irradiation were investigated. The rCF IPL-irradiated at 1,200 V improved both polar and dispersive components of surface energy, and the IFSS significantly increased by 2.93 times in relation to that of the pristine rCF and reached 95% of that of high-grade commercial CFs. We proposed a mechanism by which oxygen functional groups on the rCF surface enhance the molecular bonding force with HDPE, and the model was validated from molecular dynamics simulations. IPL irradiation is a rapid and effective surface treatment method that can be employed for the manufacture of rCF-reinforced composites.

Metformin alleviates ionizing radiation-induced senescence by restoring BARD1-mediated DNA repair in human aortic endothelial cells.

Metformin is one of the most effective therapies for treating type 2 diabetes and has been shown to also attenuate aging and age-related disorders. In this study, we explored the relationship between metformin and DNA damage repair in ionizing radiation (IR)-induced damage of human aortic endothelial cells (HAECs). Metformin treatment suppressed IR-induced senescence phenotypes, such as increased senescent-associated ß-galactosidase (SA ß-gal) activity and decreased tube formation and proliferation. Moreover, metformin increased BRCA1-associated RING domain protein 1 (BARD1) and RAD51 expression in both aging and IR-exposed cells. Metformin-treated cells exhibited higher levels of the BRCA1-BARD1-RAD51 complex during irradiation, even in the presence of compound C, an AMP-activated protein kinase inhibitor. BARD1 knockdown confirmed its critical role in metformin-mediated inhibition of endothelial senescence. Metformin increased blood vessel sprouting and decreased SA ß-gal activity in mouse aortas. Collectively, our findings provide new insights into how metformin can prevent endothelial cell senescence by promoting BARD1-related DNA damage repair, suggesting that metformin may be an effective anti-aging agent and a promising therapeutic for protecting against radiation-induced cardiotoxicity.

RPL17 Promotes Colorectal Cancer Proliferation and Stemness through ERK and NEK2/ß-catenin Signaling Pathways.

Aims: Ribosomal protein L17 (RPL17), a 60S subunit component, is up-regulated in colorectal cancer (CRC). However, its oncogenic role in CRC progression remains unexplored. Thus, we aimed to investigate the effect of RPL17 targeting on CRC in vitro and in vivo and whether RPL17 gained an extra-ribosomal function during CRC development. Methods: RPL17-specific siRNAs complexed with cationic lipids were transfected to CRC cells to silence target gene expression and then real-time RT-PCR and western blotting were applied to observe the change of expression or activity of genes or proteins of interest. Cell proliferation assay, clonogenic assay and cell cycle analysis were used to determine the in vitro effects of RPL17siRNAs on CRC cell growth, and a subcutaneous xenograft assay was applied to test the effect of RPL17siRNAs on in vivo tumor growth. RNA sequencing and western blotting were used to investigate the underlying mechanisms. Sphere-forming assay, invasion assay and migration assay were used to evaluate the effects of RPL17siRNAs on CRC stemness. Results: siRNA-mediated inhibition of RPL17 expression suppressed CRC cell growth and long-term colony formation by inducing apoptotic cell death. Similarly, targeting RPL17 effectively suppressed tumor formation in a mouse xenograft model. RNA sequencing of RPL17-silenced CRC cells revealed the same directional regulation of 159 (93 down- and 66 up-regulated) genes. Notably, NIMA-related kinase 2 (NEK2), which functionally cooperates with extracellular-regulated protein kinase (ERK) and plays a pivotal role in mitotic progression and stemness maintenance, was down-regulated. RPL17 silencing reduced NEK2, ß-catenin, and p-ERK protein levels. These molecular alterations reflected the reduction in sphere-forming capacity, expression of stem cell marker genes, migration, and invasion. Reversely, RPL17 overexpression increased the ability of long-term colony formation, migration, and invasion. Conclusion: Our findings indicate that RPL17 promotes CRC proliferation and stemness via the ERK and NEK2/ß-catenin signaling axis, and targeting RPL17 could be the next molecular strategy for both primary CRC treatment and prevention of secondary tumor formation.

Synergism of a novel MCL­1 downregulator, acriflavine, with navitoclax (ABT­263) in triple­negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.

Myeloid cell leukemia sequence 1 (MCL­1), an anti­apoptotic B­cell lymphoma 2 (BCL­2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL­1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL­1 blockers, the present study presented acriflavine (ACF) as a novel MCL­1 inhibitor in triple­negative breast cancer (TNBC). Further evaluation of its treatment potential on lung adenocarcinoma and glioblastoma multiforme (GBM) was also investigated. The anticancer effect of ACF on TNBC cells was demonstrated when MDA­MB­231 and HS578T cells were treated with ACF. ACF significantly induced typical intrinsic apoptosis in TNBCs in a dose­ and time­dependent manner via MCL­1 downregulation. MCL­1 downregulation by ACF treatment was revealed at each phase of protein expression. Initially, transcriptional regulation via reverse transcription­quantitative PCR was validated. Then, post­translational regulation was explained by utilizing an inhibitor against protein biosynthesis and proteasome. Lastly, immunoprecipitation of ubiquitinated MCL­1 confirmed the post­translational downregulation of MCL­1. In addition, the synergistic treatment efficacy of ACF with the well­known MCL­1 inhibitor ABT­263 against the TNBC cells was explored [combination index (CI)<1]. Conjointly, the anticancer effect of ACF was assessed in GBM (U87, U251 and U343), and lung cancer (A549 and NCI­H69) cell lines as well, using immunoblotting, cytotoxicity assay and FACS. The effect of the combination treatment using ACF and ABT­263 was estimated in GBM (U87, U343 and U251), and non­small cell lung cancer (A549) cells likewise. The present study suggested a novel MCL­1 inhibitory function of ACF and the synergistic antitumor effect with ABT­263.