Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

LIGHT (TNFSF14) promotes the differentiation of human bone marrow-derived mesenchymal stem cells into functional hepatocyte-like cells.

Liver transplantation is the most effective treatment option for patients with acute or chronic liver failure. However, the applicability and effectiveness of this modality are often limited by a shortage of donors, surgical complications, high medical costs, and the need for continuing immunosuppressive therapy. An alternative approach is liver cell transplantation. LIGHT (a member of the tumor necrosis factor superfamily) could be a promising candidate for promoting the differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) into hepatocyte-like cells. In this study, we investigated the effect of LIGHT on hBM-MSC differentiation into hepatocyte-like cells. Our previous results showed that LIGHT receptor lymphotoxin-ß receptor (LTßR) is constitutively expressed on the surface of hBM-MSCs. Upon treatment with recombinant human LIGHT (rhLIGHT), the phenotype of hBM-MSCs changed to round or polygonal cells. In addition, the cells exhibited high levels of hepatocyte-specific markers, including albumin, cytokeratin-18 (CK-18), CK-19, cytochrome P450 family 1 subfamily A member 1 (CYP1A1), CYP1A2, CYP3A4, SRY-box transcription factor 17 (SOX17), and forkhead box A2 (FOXA2). These results indicate that rhLIGHT enhances the differentiation of hBM-MSCs into functional hepatocyte-like cells. Furthermore, rhLIGHT-induced hepatocyte-like cells showed a higher ability to store glycogen and uptake indocyanine green compared with control cells, indicating functional progression. Additionally, treatment with rhLIGHT increased the number, viability, and proliferation of cells by inducing the S/G2/M phase and upregulating the expression of various cyclin and cyclin dependent kinase (CDK) proteins. We also found that the hepatogenic differentiation of hBM-MSCs induced by rhLIGHT was mediated by the activation of signal transducer and activator of transcription 3 (STAT3) and STAT5 pathways. Overall, our findings suggest that LIGHT plays an essential role in promoting the hepatogenic differentiation of hBM-MSCs. Hence, LIGHT may be a valuable factor for stem cell therapy.

New glucogenesis inhibition model based on complete α-glucosidases from rat intestinal tissues validated with various types of natural and pharmaceutical inhibitors.

BACKGROUND: Inhibition of intestinal α-glucosidases from rat intestinal acetone powder (RIAP) has been widely used in research focused on regulating glucogenesis to be applied as a strategy to control obesity and type II diabetes. However, the crude extract has different compositions of α-glucosidases than a complete RIAP suspension due to enzymes anchored on the intestinal tissues after the extraction. Here, the inhibitory effects of different pharmaceutical and food-grade inhibitors on the enzymes in the RIAP suspension were investigated. RESULTS: Instead of crude extracts from RIAP, the RIAP suspension without the extraction process was applied to optimize the α-glucosidase inhibitory model by pharmaceutical/natural inhibitors. The results clearly showed that the half-maximal inhibitory concentration ratios of four individual α-glucosidases by various inhibitors were different between the RIAP suspension and the crude extract. In particular, isomaltase from the RIAP suspension required more inhibitors than the crude extraction did, as this enzyme is still anchored to the remaining intestinal tissue from the extraction process. CONCLUSION: The crude extract from RIAP contains only a portion of the enzymes, which poses limitations for determining the precise inhibitory properties by various types of enzyme inhibitors. On the contrary, an in vitro assay with RIAP suspension that has all the α-glucosidases is a more suitable method for determining digestibility of glycemic carbohydrates. This new approach can be applied to the development of natural/synthetic α-glucosidase inhibitors to attenuate the postprandial glycemic response more accurately. © 2022 Society of Chemical Industry.

The c-Abl inhibitor, radotinib induces apoptosis in multiple myeloma cells via mitochondrial-dependent pathway.

Multiple myeloma (MM) is a hematological cancer resulting from accumulated abnormal plasma cells. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. Its mechanism of action involves inhibition of the tyrosine kinase Bcr-Abl and the platelet-derived growth factor receptor. Generally, the mechanism of inhibition of non-receptor tyrosine kinase c-Abl has played an essential role in the inhibition of cancer progression. However, little is known regarding the effects of the c-Abl inhibitor, radotinib on MM cells. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Interestingly, radotinib caused apoptosis in MM cells including RPMI-8226, MM.1S, and IM-9 cells, even in the absence of c-kit expression in 2 of these lines. Radotinib treatment significantly increased the number Annexin V-positive cells and decreased the mitochondrial membrane potential in MM cells. Additionally, we observed that cytochrome C was localized in the cytosol of radotinib-treated MM cells. Moreover, radotinib decreased the expression of Bcl-2 and Bcl-xL, and increased the expression of Bax and Bak in MM cells. Furthermore, radotinib promoted caspase pathway activation by inducing the expression and activity of caspase-3, -7, and -9. Expression of cleaved PARP-1 was also increased by radotinib treatment in various MM cells. In addition, radotinib significantly suppressed MM cell growth in a xenograft animal model using RPMI-8226 cells, and killed ex vivo myeloma cells from patients. In conclusion, radotinib may play an important role as a candidate agent or chemosensitizer for the treatment of MM.

LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells.

Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-ß receptor (LTßR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/ß-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTßR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.

Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death in AML cells. Therefore, we investigated combination effects of radotinib and Ara-C on AML in this study. METHODS: Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed. RESULTS: The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI-CDK-cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo. Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells. CONCLUSIONS: Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.

Time Trends for Prostate Cancer Incidence from 2003 to 2013 in South Korea: An Age-Period-Cohort Analysis.

PURPOSE: Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis. MATERIALS AND METHODS: Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence. RESULTS: Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort. CONCLUSION: PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

Different inhibition properties of catechins on the individual subunits of mucosal α-glucosidases as measured by partially-purified rat intestinal extract.

Mucosal α-glucosidases from rat intestinal powder were employed, with a step to remove α-amylase, to measure the possibility of different inhibition of catechins, particularly those found in tea, on the four α-glucosidase enzymes. Inhibition of catechins was investigated for the slowing of digestion of glycemic carbohydrates, thus regulating glucose release and absorption. The α-glucosidases were fractionated using size-exclusion chromatography. The partially purified fractions showed higher α-glucosidase activity without any α-amylase activity. Catechins had selective inhibition properties on the α-glucosidases. In particular, (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) showed comparably high inhibitory effect on all four individual α-glucosidases, while (-)-epicatechin (EC), and (+)-catechin (C) indicated a more discriminating effect with relatively higher inhibitory effects on sucrase-isomaltase. The findings suggest that catechins differently inhibit the individual subunits of the α-glucosidases, and that they could modulate postprandial blood glucose levels through slowing digestion rate of starch and other glycemic carbohydrates, including sucrose.

Photoelectrochemical Activity of Sodium Titanate Nanobelts for Photoanode.

We report photoelectrochemical characteristics of sodium titanate nanobelts as a photoanode. Sodium titanate nanobelts were synthesized by hydrothermal process using titanium(IV) tetrabutoxide in a concentrated aqueous NaOH solution. The formation mechanism of sodium titanate nanobelts in the synthetic process has been comparatively studied on the control of reaction time, pH and concentration of precursors, etc. The morphology and optical property have been investigated with X-ray diffraction, scanning electron microscope, transmission electron microscope, and ultraviolet-visible spectroscopy. On the basis of their morphological and optical characteristics, sodium titanate nanobelts were applied for photoelectrochemical cell as working electrode. After transparent film of sodium titanate nanobelts is formed on the fluorine-doped tin oxide (FTO) glass by doctor blade technique, the photoelectrochemical results were discussed on the structure of photoanode of dye sensitized solar cells.

Licochalcone A induces apoptosis in KB human oral cancer cells via a caspase-dependent FasL signaling pathway.

Licochalcone A (Lico-A) is a natural phenol licorice compound with multiple bioactivities, including anti-inflammatory, anti-microbial, anti-fungal and osteogenesis-inducing properties. In the present study, we investigated the Lico-A-induced apoptotic effects and examined the associated apoptosis pathway in KB human oral cancer cells. Lico-A decreased the number of viable KB oral cancer cells. However, Lico-A did not have an effect on primary normal human oral keratinocytes. In addition, the IC50 value of Lico-A was determined to be ~50 µM following dose-dependent stimulation. KB oral cancer cells stimulated with Lico-A for 24 h showed chromatin condensation by DAPI staining, genomic DNA fragmentation by agarose gel electrophoresis and a gradually increased apoptotic cell population by FACS analysis. These data suggest that Lico-A induces apoptosis in KB oral cancer cells. Additionally, Lico­A­induced apoptosis in KB oral cancer cells was mediated by the expression of factor associated suicide ligand (FasL) and activated caspase-8 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, in the KB oral cancer cells co-stimulation with a caspase inhibitor (Z-VAD-fmk) and Lico-A significantly abolished the apoptotic phenomena. Our findings demonstrated that Lico­A-induced apoptosis in KB oral cancer cells involves the extrinsic apoptotic signaling pathway, which involves a caspase-dependent FasL-mediated death receptor pathway. Our data suggest that Lico-A be developed as a chemotherapeutic agent for the management of oral cancer.

Fabrication of hollow metal oxide nanocrystals by etching cuprous oxide with metal(II) ions: approach to the essential driving force.

Hollow metal oxide nanocrystals were prepared by etching cuprous oxide with metal ions and were applied as photoelectrodes. As a hard template, polyvinylpyrrolidone stabilized cuprous oxide (PVP-Cu2O) and non-stabilized cuprous oxide (nPVP-Cu2O) were synthesized by a precipitation method. Hollow iron oxide and cobalt oxide nanocrystals with a truncated octahedral morphology were fabricated by an etching reaction with transition metal(II) ions (Fe(2+) or Co(2+)). In the etching reaction process, a cationic exchange reaction occurs between the divalent metal ion and Cu(+) due to the higher Lewis acidity. Facet selective etching of cuprous oxide has been observed during the ionic exchange reaction of Cu(+) and O(2-) ions in PVP-Cu2O complexes with transition metal(II) ions (Fe(2+) or Co(2+)) at the surface of a (110) facet. Amorphous states of hollow metal oxide products were annealed to form α-Fe2O3 (hematite) and Co3O4 and their crystal structure was examined with X-ray diffraction and HR-TEM. The optical absorption behavior of semiconductor nanocrystals was measured with UV-vis spectroscopy to define band gap energy. The hollow hematite structure has a 2.08 eV band gap and Co3O4 (Co(II,III) oxide) has a 1.80 eV indirect band gap. Using these hollow nanocrystals, a metal oxide monolayer film was fabricated with a secondary growth approach and was studied for its photocatalytic properties.

Discovery of new heterogeneous catalysts for the selective oxidation of propane to acrolein.

Combinatorial synthesis and screening technique have been applied to investigate the catalytic activity and selectivity of ternary and quaternary mixed-metal oxide catalysts for the selective oxidation of propane. The catalyst libraries were prepared via a modified sol-gel method using a synthesis robot and library design software, and examined for the catalytic activities in a simple high-throughput reactor system connected to a mass spectrometer for product analysis. Ternary Mo-Cr-Te, V-Cr-Sb, and Mo-V-Cr catalysts have been selected for potential candidate by composition spread approach. In a next generation composition spread library, the composition space of these three ternary compositions was sampled. Screening of this 198-member library provided substantial evidence that each ternary system has its own optimum composition where acrolein formation is highest. In addition, the composition space of the quaternary reference system Mo-V-Te-Nb mixed-oxides has also been prepared and sampled.