Critical Role of p53 Upregulated Modulator of Apoptosis in Benzyl Isothiocyanate-Induced Apoptotic Cell Death

Benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetables, decreases viability of cancer cells by causing apoptosis but the mechanism of cell death is not fully understood. The present study was undertaken to determine the role of Bcl-2 family proteins in BITC-induced apoptosis using MDA-MB-231 (breast), MCF-7 (breast), and HCT-116 (colon) human cancer cells. The B-cell lymphoma 2 interacting mediator of cell death (Bim) protein was dispensable for proapoptotic response to BITC in MCF-7 and MDA-MB-231 cells as judged by RNA interference studies. Instead, the BITC-treated MCF-7 and MDA-MB-231 cells exhibited upregulation of p53 upregulated modulator of apoptosis (PUMA) protein. The BITC-mediated induction of PUMA was relatively more pronounced in MCF-7 cells due to the presence of wild-type p53 compared with MDA-MB-231 with mutant p53. The BITC-induced apoptosis was partially but significantly attenuated by RNA interference of PUMA in MCF-7 cells. The PUMA knockout variant of HCT-116 cells exhibited significant resistance towards BITC-induced apoptosis compared with wild-type HCT-116 cells. Attenuation of BITC-induced apoptosis in PUMA knockout HCT-116 cells was accompanied by enhanced G2/M phase cell cycle arrest due to induction of p21 and down regulation of cyclin-dependent kinase 1 protein. The BITC treatment caused a decrease in protein levels of Bcl-xL (MCF-7 and MDA-MB-231 cells) and Bcl-2 (MCF-7 cells). Ectopic expression of Bcl-xL in MCF-7 and MDA-MB-231 cells and that of Bcl-2 in MCF-7 cells conferred protection against proapoptotic response to BITC. Interestingly, the BITC-treated MDA-MB-231 cells exhibited induction of Bcl-2 protein expression, and RNA interference of Bcl-2 in this cell line resulted in augmentation of BITC-induced apoptosis. The BITC-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with the induction of PUMA protein in the tumor. In conclusion, the results of the present study indicate that Bim-independent apoptosis by BITC in cancer cells is mediated by PUMA

A new record of the genus Froggattiella Leonardi (Hemiptera, Coccomorpha, Diaspididae) in South Korea

The genus Froggattiella Leonardi, 1900 belongs to the family Diaspididae, and five species of Froggattiella have been recorded worldwide. In this study, Froggattiella penicillata (Green, 1905), which attacks bamboos, is newly recorded in South Korea. The colonies of F. penicillata were collected on a bamboo forest located in Gajwa-dong, Jinju-si, Gyeongsangnam-do, South Korea (35.1599, 128.1029). Description of the adult female, host plant, adult female illustrations, and global distribution of this species are provided.Froggattiella penicillata (Green, 1905) is reported for the first time in South Korea. This species occurrs under sheathing bases of the leaves and is observed attached on the stem and not on the leaf

Notch Activation by Phenethyl Isothiocyanate Attenuates Its Inhibitory Effect on Prostate Cancer Cell Migration

Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive component of edible cruciferous vegetables with in vivo efficacy against prostate cancer in experimental rodents. Cancer chemopreventive response to PEITC is characterized by its ability to inhibit multiple oncogenic signaling pathways, including nuclear factor-κB, Akt, and androgen receptor. The present study demonstrates, for the first time, that PEITC treatment activates Notch signaling in malignant as well as normal human prostate cells. Exposure of human prostate cancer cells (LNCaP, PC-3, and DU145) and a normal human prostate epithelial cell line (PrEC) to PEITC resulted in cleavage (active form) of Notch1 and Notch2, and increased transcriptional activity of Notch. In PC-3 and LNCaP cells, PEITC treatment caused induction of Notch ligands Jagged1 and Jagged2 (PC-3), overexpression of γ-secretase complex components Presenilin1 and Nicastrin (PC-3), nuclear enrichment of cleaved Notch2, and/or up-regulation of Notch1, Notch2, Jagged1, and/or Jagged2 mRNA. PEITC-induced apoptosis in LNCaP and PC-3 cells was significantly attenuated by RNA interference of Notch2, but not by pharmacological inhibition of Notch1. Inhibition of PC-3 and LNCaP cell migration resulting from PEITC exposure was significantly augmented by knockdown of Notch2 protein as well as pharmacological inhibition of Notch1 activation. Nuclear expression of cleaved Notch2 protein was significantly higher in PC-3 xenografts from PEITC-treated mice and dorsolateral prostates from PEITC-fed TRAMP mice compared with respective control. Because Notch signaling is implicated in epithelial-mesenchymal transition and metastasis, the present study suggests that anti-metastatic effect of PEITC may be augmented by a combination regimen involving a Notch inhibitor

Effects of Glycyrrhizae Radix Pharmacopuncture Intravenous Injection on Ischemia-induced Acute Renal Failure in Rabbits

Objectives: The present study was undergone to determine whether Glycyrrhizae Radix pharmacopuncture intravenous injection exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Methods: Rabbits were treated with Glycyrrhizae Radix pharmacopuncture via i.v., followed by renal ischemia/reperfusion. The fractional excretion of glucose and phosphate were measured and the malondialdehyde content was also determined. The morphological changes of cortical part of kidney also observed with light microscope. Results: Renal ischemia/reperfusion caused increase of the fractional excretion of glucose and phosphate in ischemia-induced animals, which was prevented by Radix Glycyrrhizae extract treatment. Ischemia/reperfusion increased lipid peroxidation, which was prevented and morphological changes also altered by Radix Glycyrrhizae pharmacopuncture administration. Conclusions: These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure and Glycyrrhizae Radix pharmacopuncture exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion

Aluminum nitride waveguide beam splitters for integrated quantum photonic circuits

We demonstrate integrated photonic circuits for quantum devices using sputtered polycrystalline aluminum nitride (AlN) on insulator. The on-chip AlN waveguide directional couplers, which are one of the most important components in quantum photonics, are fabricated and show the output power splitting ratios from 50:50 to 99:1. The polarization beam splitters with an extinction ratio of more than 10 dB are also realized from the AlN directional couplers. Using the fabricated AlN waveguide beam splitters, we observe the Hong-Ou-Mandel interference with a visibility of 91.7 +(-) 5.66 %.Comment: 9 pages, 4 figure

Endoscopic Ultrasound-Guided Drainage without Fluoroscopic Guidance for Extraluminal Complicated Cysts

Background. Endoscopic ultrasound- (EUS-) guided drainage is generally performed under fluoroscopic guidance. However, improvements in endoscopic and EUS techniques and experience have led to questions regarding the usefulness of fluoroscopy. This study aimed to retrospectively evaluate the safety and efficacy of EUS-guided drainage of extraluminal complicated cysts without fluoroscopic guidance. Methods. Patients who had undergone nonfluoroscopic EUS-guided drainage of extraluminal complicated cysts were enrolled. Drainage was performed via a transgastric, transduodenal, or transrectal approach. Single or double 7 Fr double pigtail stents were inserted. Results. Seventeen procedures were performed in 15 patients in peripancreatic fluid collections (n=13) and pelvic abscesses (n=4). The median lesion size was 7.1 cm (range: 2.8–13.0 cm), and the mean time spent per procedure was 26.2±9.8 minutes (range: 16–50 minutes). Endoscopic drainage was successful in 16 of 17 (94.1%) procedures. There were no complications. All patients experienced symptomatic improvement and revealed partial to complete resolution according to follow-up computed tomography findings. Two patients developed recurrent cysts that were drained during repeat procedures, with eventual complete resolution. Conclusion. EUS-guided drainage without fluoroscopic guidance is a technically feasible, safe, and effective procedure for the treatment of extraluminal complicated cysts

Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach

© 2020, The Author(s).Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

Inactivated vaccine with glycyrrhizic acid adjuvant elicits potent innate and adaptive immune responses against foot-and-mouth disease

BackgroundFoot-and-mouth disease (FMD) is an extremely contagious viral disease that is fatal to young animals and is a major threat to the agricultural economy by reducing production and limiting the movement of livestock. The currently commercially-available FMD vaccine is prepared using an inactivated viral antigen in an oil emulsion, with aluminum hydroxide [Al(OH)3] as an adjuvant. However, oil emulsion-based options possess limitations including slow increases in antibody titers (up to levels adequate for defense against viral infection) and risks of local reactions at the vaccination site. Further, Al(OH)3 only induces a T helper 2 (Th2) cell response. Therefore, novel adjuvants that can address these limitations are urgently needed. Glycyrrhizic acid (extracted from licorice roots) is a triterpenoid saponin and has great advantages in terms of price and availability.MethodsTo address the limitations of the currently used commercial FMD vaccine, we added glycyrrhizic acid as an adjuvant (immunostimulant) to the FMD bivalent (O PA2 + A YC) vaccine. We then evaluated its efficacy in promoting both innate and adaptive (cellular and humoral) immune reactions in vitro [using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs)] and in vivo (using mice and pigs).ResultsGlycyrrhizic acid has been revealed to induce an innate immune response and enhance early, mid-, and long-term immunity. The studied bivalent vaccine with glycyrrhizic acid increased the expression of immunoregulatory genes such as pattern-recognition receptors (PRRs), cytokines, transcription factors, and co-stimulatory molecules.ConclusionCollectively, glycyrrhizic acid could have utility as a novel vaccine adjuvant that can address the limitations of commercialized FMD vaccines by inducing potent innate and adaptive immune responses