Search

Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ-33 is a quinazolinone derivative with proposed anticancer activities that was synthesized in our laboratory. The present study aimed to evaluate the anticancer activity of MJ-33 in fluorouracil (5FU)-resistant colorectal cancer cells (HT-29/5FUR) and to investigate the underlying molecular mechanisms. The cell viability assay results indicated that HT-29/5FUR cell viability was inhibited by MJ-33 treatment in a concentration-dependent manner compared with the control group. The cellular morphological alterations observed following MJ-33 treatment indicated the occurrence of apoptosis and autophagy, as well as inhibition of cell proliferation in a time-dependent manner compared with the control group. The acridine orange, LysoTracker Red and LC3-green fluorescent protein staining results indicated that MJ-33 treatment significantly induced autophagy compared with the control group. The DAPI/TUNEL dual staining results demonstrated increased nuclear fragmentation and condensation following MJ-33 treatment compared with the control group. The Annexin V apoptosis assay and image cytometry analysis results demonstrated a significant increase in apoptotic cells following MJ-33 treatment compared with the control group. The western blotting results demonstrated markedly decreased Bcl-2, phosphorylated (p)-BAD, pro-caspase-9 and pro-caspase-3 expression levels, and notably increased cytochrome c and apoptotic peptidase activating factor 1 expression levels following MJ-33 treatment compared with the control group. Moreover, the expression levels of autophagy-related proteins, including autophagy related (ATG)-5, ATG-7, ATG-12, ATG-16, p62 and LC3-II, were increased following MJ-33 treatment compared with the control group. Furthermore, MJ-33-treated HT-29/5FUR cells displayed decreased expression levels of p-AKT and p-mTOR compared with control cells. The results suggested that MJ-33-induced apoptosis was mediated by AKT signaling, and subsequently modulated via the mitochondria-dependent signaling pathway. Therefore, the results suggested that suppression of AKT/mTOR activity triggered autophagy in the HT-29/5FUR cell line. In summary, the results indicated that MJ-33 inhibited HT-29/5FUR cell viability, and induced apoptosis and autophagy via the AKT/mTOR signaling pathway. The present study may provide novel insight into the anticancer effects and mechanisms underlying MJ-33 in 5FU-resistant colorectal cancer cells.

Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco. Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro, with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of β-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing.

A series of 4'-acylamino modified Δ1,4-pregnadien-21E-benzylidene-3,20-dione derivatives (6a-v) was synthesized from the commercially available progesterone (1). These title compounds were evaluated for their toxicity against brine shrimp (Artemia salina) and cytotoxic activities against two human cancer cell lines (HeLa and MCF-7). The results revealed that compound 6f exhibited promising in vitro cytotoxic activity to the two cancer cell lines and the nature of acylamino functional group in the benzylidene moiety had a significant influence on cytotoxicity.

Using progesterone as the starting material, we synthesized a series of steroidal derivatives possessing a D-ring substituted benzamidothiazole. All of the final structures were reported and identified by NMR and HRMS spectrometry for the first time. The antiproliferative activity of the synthesized compounds against PC-3 (human prostate cancer cell line) and SKOV-3 (ovarian cancer cells) were investigated. The preliminary results showed that compounds 8b, 8d and 8g possessed moderate antiproliferative activities.

The synthesis of steroidal derivatives containing [1,2,4]triazolo[1,5- a]pyrimidine derived from progesterone is described. The Claisen condensations of Δ1,4-pregnadien-3,20-dione and 4-chloro-Δ1,4-pregnadien-3,20-dione with dimethyl oxalate afforded 21-methoxalylpregn-1,4-diene-3,20-dione and 4-chloro-21-methoxalylpregn-1,4-diene-3,20-dione, respectively. Furthermore, the reactions of these compounds with 3-amino-1,2,4-triazole yielded the corresponding [1,2,4]triazolo[1,5- a]pyrimidine derivatives. The newly synthesised compounds were evaluated in vitro by means of sulforhodamine B assays for antiproliferative activity against HeLa and MCF-7 cells.

T253 paper presents a method of automatic control system based on thirty-seven xenon lamps for simulated solar radiation in space environment. The control system is divided into the control terminal and the executive terminal, which can process the function calls and data interaction between eachother. According to the actual feedback of the test data, the system can adjust the drive output; automatically achieve the test process to reduce artificial operation. The system includes xenon lamp supply system, xenon lamp trigger system, lighting control system, irradiance detection system and irradiance automatic control system, which achieve the functions of the xenon lamp fault detection, xenon lamp circuit protection, xenon lamp anodic temperature monitoring function and xenon lamp life estimation function. The automatic control of the light source is great significance for the development of the solar simulator.

Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene. Pterostilbene also effectively inhibited cell viability and suppressed cell confluence in a time- and concentration-dependent manner. Probing with acridine orange, monodansylcadaverine and LysoTracker Red demonstrated that the number of acidic vesicular organelles was increased, indicating increased autophagy. Furthermore, Heochst 33342 staining determined that DNA condensation, a characteristic of apoptosis, was enhanced following treatment with pterostilbene. Furthermore, pterostilbene upregulated mRNA levels of LC3-II and Atg12, as well as the expression of Atgs/Beclin-1/LC3-associated signaling, suggesting that it enhances autophagy. The autophagy inhibitors 3-methyladenine and chloroquine were used to confirm that pterostilbene induces autophagy. It was also determined that pterostilbene triggered caspase-dependent apoptosis by directly testing DNA breakage and using the pan-caspase inhibitor carbobenzoxyvalyl-alanyl-aspartyl fluoromethyl ketone. The results demonstrated that pterostilbene mediates the apoptosis of CAR cells via the intrinsic apoptotic cascade. In addition, pterostilbene inhibited MDR1 expression and the phosphorylation of AKT on the Ser473 site in CAR cells. Therefore, pterostilbene may elicit an oral anticancer response in drug-resistant cells and may be used as a chemotherapeutic adjuvant to treat patients with oral cancer.

Oral squamous cell carcinoma (OSCC) is a type of cancer with high morbidity and mortality rates worldwide; it also demonstrates chemotherapeutic resistance. Triterpenoid ursolic acid has been shown to exhibit various biological activities and anticancer effects in several preclinical studies. In our previous study, human cisplatin‑resistant oral cancer CAR cells were established, and the present study aimed to further examine the effects of ursolic acid on CAR cells. The results revealed that ursolic acid inhibited CAR cell viability, as determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Ursolic acid‑induced cell death was mediated through a caspase‑dependent pathway, determined with the pan‑caspase inhibitor, z‑VAD‑fmk. Ursolic acid also increased the activities of caspase‑3 and caspase‑9 in CAR cells, determined by a colorimetric assay. Specifically, the production of reactive oxygen species and loss of mitochondrial membrane potential, detected by flow cytometry, were observed in the ursolic acid‑treated CAR cells. The apoptosis‑associated signaling showed that ursolic acid decreased the phosphorylation of AKT (Ser473) and B‑cell lymphoma 2 (Bcl‑2)‑associated agonist of cell death (BAD; Ser136), and the protein levels of Bcl‑2 and Bcl‑extra large (Bcl‑xL), and increased the expression of BAD and Bcl‑2‑associated X (Bax) protein in CAR cells. In summary, the results supported the potential application of ursolic acid against drug‑resistant oral carcinoma and to improve oral anticancer efficacy in the near future.

Background/aim Gadoxetate disodium (Primovist or Eovist) is extensively used as a hepatospecific contrast agent during magnetic resonance imaging (MRI) examinations. However, there is no information determining whether gadoxetate disodium has a cytotoxic impact and/or affects relative gene expression on liver cells. In the current study, we investigated the effects of gadoxetate disodium on cytotoxicity and the levels of gene expression in human normal Chang Liver cells. Materials and methods The cytotoxic effect was detected via methyl thiazolyl tetrazolium (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining. mRNA expression was monitored by cDNA microarray and quantitative PCR (qPCR) analysis. The protein levels were determined by western blotting. Results Gadoxetate disodium at 5 and 10 mM failed to induce any cell cytotoxicity and morphological changes in Chang Liver cells. Our data demonstrated that gadoxetate disodium significantly enhanced the expression of 29 genes and suppressed that of 27. The SLCO1C1 (solute carrier organic anion transporter family member 1C1) mRNA expression was also increased by 2.62-fold (p-value=0.0006) in gadoxetate disodium-treated cells. Furthermore, we also checked and found that gadoxetate disodium up-regulated organic anion transporter polypeptide 1B1 (OATP1B1) protein level and increased OATP uptake transporter gene SLCO1C1 mRNA expression. Conclusion Our results provide evidence regarding that gadoxetate disodium might be no cytotoxic effects on liver cells.

Thermal diffusivity of eutectic formed in aqueous alkali chloride solutions (NaCl, KCl, RbCl and CsCl) was determined by temperature wave analysis (TWA) during the freezing–thawing process of aqueous alkali chloride solution. An obvious change of thermal diffusivity in freezing–thawing processes of eutectic was observed with the super-cooling phenomena for each alkali chloride solute. The rate of thermal diffusivity decrease during the eutectic melting in comparison to the total decrease from the solid to the liquid state was observed larger than that of the heat of fusion measured by DSC, especially in the dilute concentration. It was confirmed that thermal diffusivity was sensitively influenced by the highly structure of the coexistence of eutectic crystallization and ice.

The effect of cryoprotectants (sucrose, glucose, dimethyl sulfoxide (DMSO) and polyvinylpyrrolidone (PVP)) on the eutectics of NaCl·2H2O/ice and KCl/ice have been studied by temperature wave analysis (TWA) and differential scanning calorimetry (DSC). The eutectic crystallization was inhibited by the cryoprotectant, and a higher inhibitory ability was observed in NaCl systems (water/NaCl/cryoprotectant) than in KCl systems (water/KCl/cryoprotectant) with the same additive concentration. In the above system, sugars showed the higher inhibition ability than DMSO or PVP. The increase of thermal diffusivity with the increasing sugar concentration at a temperature immediately after the eutectic melting in KCl/sugar systems suggested a characteristic hydration of sugar and K+ ion, this was not observed in NaCl/sugar systems.

Some of the synthesized compounds (III) (14 examples) exhibit significant cytotoxic activities.

Agrochemical research, over the last two decades, has resulted in the discovery of chemically novel insecticides, of which steroids-based compounds that mimic the action of hormones have been considered as safe insecticides. In this study, eight steroidal C-17 pyrazolinyl derivatives were resynthesized through molecular hybridization and their insecticidal activities against 4thinstar larvae of Mythimna separate were evaluated. These results showed that some compounds exhibited significant insecticidal activities and the susceptibility assays were expressed as the median lethal dose (LD50), of which one of the compounds exerted the most potent insecticidal activity (LD50 = 296 µg g-1), comparable to that of the natural product insecticide, celangulatin V (LD50 = 260 µg g-1). This strategy led to a promising candidate for the development of new steroidal insecticidal agents.

Fourteen novel steroidal C-17 pyrazolinyl derivatives 9a – g and 10a – g were synthesized from commercially available progesterone and tested for their cytotoxic activity against brine shrimp ( Artemia salina ) and three human cancer cell lines (NCI-H460, HeLa, and HepG2). Some of these synthetic compounds exhibited significant cytotoxic activity, and treatment of HeLa cells with compound 10b resulted in the cell population arrest in the S phase. A structure–activity relationship was discussed.

A series of novel derivatives of 21 E -benzylidene-pregn-1,4-diene-3,20-dione 7a–g and 21 E -benzylidene-4-chloro-pregn-1,4-diene-3,20-dione 8a–g was synthesized from the commercially available progesterone. These title compounds were evaluated for their cytotoxic activity against brine shrimp ( Artemia salina ) and murine Lewis lung carcinoma cells (LLC). It was found that compounds 7a–g exhibited stronger activities than 8a–g against the brine shrimps, and some of the tested compounds possessed weak inhibition of LLC cells.

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors, which play a key role in modulating glucose and lipid metabolism and in the pathogenesis of atherosclerosis. Ginsenosides are the active components of ginseng, which is a perennial aromatic herb that is widely used in China for medicinal purposes. Some studies have reported that ginsenosides have anti-hyperglycemia and anti-obesity effects that involve the PPAR-mediated pathway. The aims of this study were to investigate mononuclear macrophage PPARgamma mRNA expression of type 2 diabetes and the effect of ginsenosides on PPARgamma mRNA expression and glucose and lipid metabolism. Our results showed that subjects with type 2 diabetes had lower PPARgamma mRNA levels compared with normal controls. Following 2 weeks of 41 mg/day ginsenoside treatment, the expression of PPARgamma mRNA in patients with type 2 diabetes was significantly increased, the total cholesterol and triglyceride levels were significantly decreased, and the blood glucose level also decreased (but without statistical significance) compared to the control group. These results demonstrated that ginsenosides improved PPARgamma expression and lipid metabolism. Thus, ginsenosides may be applied as an adjuvant for treating type 2 diabetes.

Ionizing irradiation effects on MBS (metal-BOX-silicon) have been studied in this paper. Through pre- and post-irradiation high-frequency (HF) C-V curves of MBS of several samples in which fluorine was implanted into BOX of SIMOX, it was found that PD fluoridated SIMOX is beneficial to harden buried oxide layer

In an effort to manipulate the bond strengths of hydrogen bonds, we have studied a three-component chemical system consisting of a reaction center, a conjugated bridge, and a hydrogen-bonding site. Protonation of the reaction center triggers intramolecular charge transfer from the hydrogen-bonding site, altering its affinity to bind to an acceptor. Previously, we had found that this communication (signal transduction) between the reaction center and the hydrogen-bonding site does not necessarily die out with increasing length of the conjugated bridge. In certain cases, this signal transduction is maintained-and even amplified-over long distances (I. Chao, T.-S. Hwang, Angew. Chem. 2001, 113, 2775-2777; Angew. Chem. Int. Ed. 2001, 40, 2703-2705). In this study we report the results of an extensive theoretical investigation of this problem to provide insights into this intriguing phenomenon. In the systems we investigated it was found that the push-pull process between the hydrogen-bonding site and the protonatable reaction center was mediated with the greatest facility by conjugated bridges with low-lying pi and pi* orbitals.

Electrolyzed water accelerated the healing of full-thickness cutaneous wounds in rats, but only anode chamber water (acid pH or neutralized) was effective. Hypochlorous acid (HOCl), also produced by electrolysis, was ineffective, suggesting that these types of electrolyzed water enhance wound healing by a mechanism unrelated to the well-known antibacterial action of HOCl. One possibility is that reactive oxygen species, shown to be electron spin resonance spectra present in anode chamber water, might trigger early wound healing through fibroblast migration and proliferation.

The title compound, C15H13BrO3, was synthesized by the benz­yl esterification of 5-bromo-4-methyl­salicylic acid. The mol­ecular conformation is stabilized by an intra­molecular hydrogen bond.

The asymmetric unit of the title compound, C12H9NO2S4, contains one half-molecule with the N, two S amd four C atoms lying on a mirror plane. The molecule exhibits a V-shaped conformation, with a dihedral angle of 87.00 (7)° between the benzene and dithiolopyrrole rings. The methyl group was treated as rotationally disordered between two orientations in a 1:1 ratio. In the crystal, weak C—H...O hydrogen bonds link the molecules into chains in [010].

In the title compound, C8H8S6, the five-membered rings form a dihedral angle of 25.06 (9)°. In the absence of short intermolecular contacts, the molecules are packed by van der Waals forces in the crystal.

In order to improve the total-dose radiation hardness of the buried oxide of separation by implanted oxygen silicon-on-insulator wafers, nitrogen ions were implanted into the buried oxide with a dose of 1016 cm−2, and subsequent annealing was performed at 1100 °C. The effect of annealing time on the radiation hardness of the nitrogen implanted wafers has been studied by the high frequency capacitance-voltage technique. The results suggest that the improvement of the radiation hardness of the wafers can be achieved through a shorter time annealing after nitrogen implantation. The nitrogen-implanted sample with the shortest annealing time 0.5 h shows the highest tolerance to total-dose radiation. In particular, for the 1.0 and 1.5 h annealing samples, both total dose responses were unusual. After 300-krad(Si) irradiation, both the shifts of capacitance-voltage curve reached a maximum, respectively, and then decreased with increasing total dose. In addition, the wafers were analysed by the Fourier transform infrared spectroscopy technique, and some useful results have been obtained.

In this work, we investigate the effects of the indium ion implantation towards the back-channel interface on the total dose hardness of the n-channel SOI MOSFET. The results show that the indium implant has slight impact on the normal threshold voltage while preserving low leakage current after irradiation. The advantage is attributed to the narrow as-implanted and postanneal profile of the indium implantation. Two-dimensional simulations have been used to understand the physical mechanisms of the effects.

InP/SiO2 composite thin films have been deposited on hot substrates of slice of silica glass and polished silicon by a radio frequency magnetron co-sputtering technique, and annealing under several conditions. Detailed analysis of the composition of the films by X-ray photoelectron spectroscopy and Rutherford backscattering spectroscopy shows that the InP and SiO2 exist in normal stoichiometry as a whole. X-ray diffraction patterns and Raman spectra of the films conform the presence of InP nanocrystals in the composite films. Very small amounts of extra indium and In2O3 have been removed and pure InP/SiO2 nanocomposite films have been obtained by annealing at high temperature (520℃) in over-pressure of phosphorous vapor. Blue shifts of optical absorption spectra and great enhancement of optical nonlinearity of the films at room temperature have been observed.