Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells.

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy.

Unravelling Disorder Effects on Thermoelectric Properties of Semicrystalline Polymers in a Wide Range of Doping Levels.

Thermoelectric (TE) performance of a specific semicrystalline polymer is studied experimentally only in a limited range of doping levels with molecular doping methods. The doping level is finely controlled via in situ electrochemical doping in a wide range of carrier concentrations with an electrolyte ([PMIM]+ [TFSI]- )-gated organic electrochemical transistor system. Then, the charge generation/transport and TE properties of four p-type semicrystalline polymers are analyzed and their dynamic changes of crystalline morphologies and local density of states (DOS) during electrochemical doping are compared. These polymers are synthesized based on poly[(2,5-bis(2-alkyloxy)phenylene)-alt-(5,6-difluoro-4,7-di(thiophene-2-yl)benzo[c][1,2,5]thiadiazole)] by varying side chains: With oligoethylene glycol (OEG) substituents, facile p-doping is achieved because of easy penetration of TFSI- ions into the polymer matrix. However, the charge transport is hindered with longer OEG chains length because of the enhanced insulation. Therefore, with the shortest OEG substituents the electrical conductivity (30.1 S cm-1 ) and power factor (2.88 µW m-1 K-2 ) are optimized. It is observed that all polymers exhibit p- to n-type transition in Seebeck coefficients in heavily doped states, which can be achieved by electrochemical doping. These TE behaviors are interpreted based on the relation between the localized DOS band structure and molecular packing structure during electrochemical doping.

A botulinum neurotoxin-like function of Potentilla chinensis extract that inhibits neuronal SNARE complex formation, membrane fusion, neuroexocytosis, and muscle contraction.

CONTEXT: Botulinum neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis. OBJECTIVE: In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated. MATERIALS AND METHODS: After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined. RESULTS: The extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 µg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca²âº-channel blocker verapamil and BoNT type A. DISCUSSION AND CONCLUSION: While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the Potentilla chinensis extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics.

Impacts of Transitioning to an Online Curriculum at a Graduate School in South Korea Due to the COVID-19 Pandemic.

This study focuses on the impacts of implementing an online curriculum at a graduate school in South Korea in response to the COVID-19 pandemic. A framework distinguishing impacts to academic, educational, and institutional stakeholders from the virtualization of curricula as well as general COVID-19 prevention measures is invoked to help understand the impacts of these changes. These impacts are sourced from general graduate school operations, course evaluations for two compulsory courses, and unofficial interviews with students and professors. A statistical evaluation of the course evaluations suggested no significant difference between the online format of 2020 and the traditional in person formats in prior years in terms of academics and education. Unofficial meetings with students and faculty revealed technical issues throughout 2020, which many could not be resolved due to the variety of different computer systems at the school as well as limited technical support. Most importantly, students stated they were suffering from prolonged mental and emotional distress such as feeling isolated. Lessons learned include having academic institutions prepare for difficulties in technical support, educational infrastructure investments, compliance, as well as student body mental health.

Inhibition of cell cycle progression via p27Kip1 upregulation and apoptosis induction by an ethanol extract of Rhus verniciflua Stokes in AGS gastric cancer cells.

Botanical preparations are widely used by patient with cancer in Korea, Japan and China. Rhus verniciflua Stokes (RVS) has traditionally been used as a medicinal ingredient for the therapy of stomach and uterine cancer. In this study, we showed that exposure to an ethanol extract of RVS (50 microg/ml) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces G1-cell cycle arrest through the regulation of cyclins, the induction of p27Kip1, and decrease the CDK2 kinase activity. The upregulated p27Kip1 level is caused by protein stability increment by the reduction of Skp2, a key molecule related with p27Kip1 ubiquitination and degradation, and de novo protein synthesis. RVS extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces G1-cell cycle arrest via accumulation of p27Kip1 controlled by Skp2 reduction and apoptosis passing through an intrinsic pathway in human gastric cancer cells but not in normal cells, therefore we suggest that this extract could be a candidate medicine or compound for the development of novel class of anti-cancer drugs.

Effect of partially hydrolyzed soluble glucan produced by glucosyltrasferases of Streptococcus mutans on stimulating human T cell.

Soluble glucan, which was obtained from action of glucosyltransferases (GTFs) of Streptococcus mutans on sucrose, was partially hydrolyzed by acetic acid and examined for human T lymphoblast (MOLT-4) stimulating activity. Addition of the partially hydrolyzed glucan (15-60 microg/ml) stimulated human T cell (39-65%) in a dose dependant manner according to MTT assay. Production of interleukine-2 (IL-2) and interleukine-2 receptor (IL-2R) from T cell was increased by 44.5 and 25%, respectively, by addition of partially hydrolyzed glucan (15 microg/ml). These results indicate that stimulation of human T cells by hydrolyzed glucan is probably caused by its effects on stimulating gene expression of IL-2 and IL-2R of human T cell.

Effects of wild ginseng (Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats.

The aim of this study was to examine the possible antioxidant activities of wild Panax ginseng leaf extract intake in streptozotocin (STZ)-induced diabetic rats (WGLE). Initial blood glucose levels increased abruptly after streptozotocin injection. After 4 weeks of WGLE supplementation, blood glucose levels were lower in animals fed 40 mg/kg (266 mg/dL) and 200 mg/kg (239 mg/dL) than those in no-WGLE fed diabetic rats (464 mg/dL). The concentration of blood TBARS, which are considered the main products of glucose oxidation in blood, was also lowered by WGLE supplementation. These results indicate that WGLE supplementation is involved in suppressing a sudden increase in blood glucose levels and a consequent decrease in TBARS levels in diabetic rats. TBARS levels in the liver, kidney and spleen of WGLE-fed diabetic groups were also significantly lower than in the control diabetic group indicating that oral administration of WGLE effectively suppresses lipid peroxidation that occurs in the organs of diabetic rats. Antioxidant activities of WGLE supplementation further extend in suppressing activities of antioxidant related enzymes, such as glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), in organs of diabetic rats. These results confirm the effectiveness of WGLE supplementation in detoxifying free radicals that are produced excessively in diabetic-induced complications.

Comparison of resorbable plates and titanium plates for fixation stability of combined mandibular symphysis and angle fractures.

OBJECTIVES: We compared resorbable plates with titanium plates for treatment of combined mandibular angle and symphyseal fractures. MATERIALS AND METHODS: Patients with mandibular angle and symphysis fractures were divided into two groups. The control (T) group received titanium plates while the experimental (R) group received resorbable plates. All procedures were carried out under general anesthesia using standard surgical techniques. We compared the frequency of wound dehiscence, development of infection, malocclusion, malunion, screw breakage, and any other technical difficulties between the two groups. RESULTS: Thirteen patients were included in the R group, where 39 resorbable plates were applied. The T group consisted of 16 patients who received 48 titanium plates. The mean age in the R and T groups was 28.29 and 24.23 years, respectively. Primary healing of the fractured mandible was obtained in all patients in both groups. Postoperative complications were minor and transient. Moreover, there were no significant differences in the rates of various complications between the two groups. Breakage of 3 screws during the perioperative period was seen in the R group, while no screws or plates were broken in the T group. CONCLUSION: Resorbable plates can be used to stabilize combined mandibular angle and symphysis fractures.

Identification of an anticancer compound against HT-29 cells from Phellinus linteus grown on germinated brown rice.

OBJECTIVE: To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate (EtOAc) extract of Phellinus linteus grown on germinated brown rice (PB). METHODS: EtOAc extract of PB was partitioned with n-hexane, EtOAc, and water-saturated n-butanol. Anticancer compound of n-hexane layer was isolated and identified by HPLC and NMR, respectively. Cytotoxicity against HT-29 cells was tested by SRB assay. RESULTS: The n-hexane layer obtained after solvent fractionation of PB EtOAc extracts showed a potent anticancer activity against the HT-29 cell line. Atractylenolide I, a eudesmane-type sesquiterpene lactone, a major anticancer substance of PB, was isolated from the n-hexane layer by silica gel column chromatography and preparative-HPLC. This structure was elucidated by one- and two-dimensional NMR spectroscopic data. Atractylenolide I has not been reported in mushrooms or rice as of yet. The isolated compound dose-dependently inhibited the growth of HT-29 human colon cancer cells. CONCLUSIONS: Atractylenolide I might contribute to the anticancer effect of PB.

Stimulation of various functions in murine peritoneal macrophages by glucans produced by glucosyltransferases from Streptococcus mutans.

The glucan that was produced by glucosyltransferases (GTFs) from Streptococcus mutans was examined for its stimulating functions toward murine peritoneal macrophages. Soluble glucan was obtained by the reaction with cell-free crude GTFs and sucrose, followed by ethanol precipitation, dispersion in water and re-precipitation by ethanol. Soluble glucan, those average molecular weight was about 3 x 10(5), was composed of mixture of alpha-1,6 and alpha-1,3 linkages in a 3:1 ratio. When 30 and 60 microg/ml of the glucan was incubated with peritoneal macrophages, the lysosomal phosphatase activity was increased in a dose-dependent manner, indicating that soluble glucan may activate macrophages. To examine its effects on the various functions of macrophages, soluble glucan was orally administered daily at a level of 100 mg/kg of body weight to C57BL/6 mice. Significant stimulation of the production of H2O2 by the macrophages was observed without any increase in NO production. The production of tumor necrosis factor-alpha (TNF-alpha) by the macrophages was also stimulated from 538.73-555.06 pg/ml to 585.73-596.40 pg/ml during 15 days of oral administration of soluble glucan. The cytotoxicity of peritoneal macrophages against B16 tumor cells was significantly enhanced by 25-38% during 15 days of oral administration. These results may indicate that soluble glucan stimulates the immune functions of macrophages.