Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from mitochondria to the ER in cancer cells

Background: Resistance to cell death in the presence of stressful stimuli is one of the hallmarks of cancer cells acquired during multistep tumorigenesis, and knowledge of the molecular mechanism of stress adaptation can be exploited to develop cancer-selective therapeutics. Mitochondria and the endoplasmic reticulum (ER) are physically interconnected organelles that can sense and exchange various stress signals. Although there have been many studies on stress propagation from the ER to mitochondria, reverse stress signals originating from mitochondria have not been well reported.Methods: After inactivation of the proteins by pharmacologic and genetic methods, the signal pathways were analyzed by fluorescence microscopy, flow cytometry, MTT assay, and western blotting. A mouse xenograft model was used to examine synergistic anticancer activity and the action mechanism of drugs in vivo.Results: We show in this study that mitochondrial heat shock protein 90 (Hsp90) suppresses mitochondria-initiated calcium-mediated stress signals propagating into the ER in cancer cells. Mitochondrial Hsp90 inhibition triggers the calcium signal by opening the mitochondrial permeability transition pore and, in turn, the ER ryanodine receptor, via calcium-induced calcium release. Subsequent depletion of ER calcium activates unfolded protein responses in the ER lumen, thereby increasing the expression of a pro-apoptotic transcription factor, CEBP homologous protein (CHOP). Combined treatment with the ER stressor thapsigargin and the mitochondrial Hsp90 inhibitor gamitrinib augmented interorganelle stress signaling by elevating CHOP expression, and showed synergistic cytotoxic activity exclusively in cancer cells in vitro and in vivo.Conclusions: Collectively, mitochondrial Hsp90s confer cell death resistance to cancer cells by suppressing the mitochondria-initiated calcium-mediated interorganelle stress response.open0

ANTERIOR CRUCIATE LIGAMENT INJURY RISK FACTORS DIFFERENCES BETWEEN FEMALE DANCERS AND FEMALE SOCCER PLAYERS DURING SINGLE-LEGGED AND DOUBLE LEGGED LANDING TASKS

The purpose of this study was to compare ACL injury risk factors between female dancers and female soccer players during single-legged drop landing and double legged drop landing vertical jump tasks. Fifteen elite female soccer players and 45 professional female dancers (15 ballet, 15 modern, and 15 Korean dancers) were recruited to participate in this study. Two-way repeated measure of ANOVAs (participant groups & landing tasks, 4x2) were used. Female dancers landed with a significantly lower trunk flexion, trunk external rotation, knee external rotation, and knee valgus moment than those of female soccer players. Also, single-legged drop landing task demonstrated a higher trunk external rotation and knee valgus moment than those of double legged drop landing vertical jump task

Silicon improves growth and antioxidative defense system in salt-stressed Kentucky bluegrass (Poa pratensis L.), ‘Perfection’ and ‘Midnight’

After 400 mM of NaCl treatment, 0.1 and 1.0 mM of silicon (Si) were added to Kentucky bluegrass, ‘Perfection’ and ‘Midnight,’ to identify the effect of Si on the antioxidant defense mechanisms and inorganic ions as a parameter in the salt stress on grass. Compared to the control, the NaCl treatment caused a significant decrease in the shoot length and the fresh and dry weight of shoot and root of the both types of Kentucky bluegrass. Adding Si after the NaCl treatment increased the growth and dry and fresh weight of shoot and root in the grass. In both types, the Na+ concentration significantly increased after the NaCl-only treatment compared to control and decreased dramatically after 0.1 and 1.0 mM Si were added following the NaCl treatment compared to the NaCl-only treatment. K+ and Si concentrations remarkably increased in the shoot and root when Si was added after NaCl treatment. There was a significant reduction in the oxygen radical absorption capacity and the total phenolic compounds in the both types. Compared to the NaCl-only treatment, higher glutathione and lower proline concentrations were observed in the plant treated with Si after NaCl treatment. These results suggest that, even though Si is not generally classified as ‘essential element’, Si may have a significant involvement in the antioxidant defense mechanisms and inorganic ions in the salt stress on grass.Key words: diphenyl-1-picrylhydrazyl (DPPH), total phenolic concentration, proline, salt stress

Viable stretchable plasmonics based on unidirectional nanoprisms

Well-defined ordered arrays of plasmonic nanostructures were fabricated on stretchable substrates and tunable plasmon-coupling-based sensing properties were comprehensively demonstrated upon extension and contraction. Regular nanoprism patterns consisting of Ag, Au and Ag/Au bilayers were constructed on the stretchable polydimethylsiloxane substrate. The nanoprisms had the same orientation over the entire substrate (3 x 3 cm(2)) via metal deposition on a single-crystal microparticle monolayer assembly. The plasmonic sensor based on the Ag/Au bilayer showed a 6-fold enhanced surface enhanced Raman scattering signal under 20% uniaxial extension, whereas a 3-fold increase was observed upon 6% contraction, compared with the Au nanoprism arrays. The sensory behaviors were corroborated by finite-difference time-domain simulation, demonstrating the tunable electromagnetic field enhancement effect via the localized surface plasmon resonance coupling. The advanced flexible plasmonic-coupling-based devices with tunable and quantifiable performance herein suggested are expected to unlock promising potential in practical bio-sensing, biotechnological applications and optical devices.11Ysciescopu

Cell-free synthesis of functional phospholipase A1 from Serratia sp.

Additional file 1: Figure S1 Gas chromatography analysis of sesame oil incubated with cell-free synthesized PLA1

Establishment of a piglet model for peritoneal metastasis of ovarian cancer

Background : A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to establishing innovative chemotherapeutical and surgical strategies without any limitation on rodent models. Methods : A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with laparoscopic surgery. In phase I trial, 5.0 × 106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0 × 106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns within the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to 4 weeks after inoculation. Tumor tissues disseminated in the peritoneum 4 weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining. Results : In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at 3 weeks after the first inoculation, which increased to 14 and 15 after 4 weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at 4 weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Immunohistochemical H&E and PAX-8 staining confirmed metastatic tumors. Conclusions : This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cell lines from humans. Using two cell lines, the PM rate is 75%.This research was supported by a grant from Seoul National University (No,800–20190437). Moreover, Commercializations Promotion Agency for R&D Outcomes supported this research with a grant funded by the Korea government (the Ministry of Science and ICT; No. 1711151316)