Effect of a multi-layer infection control barrier on the micro-hardness of a composite resin

OBJECTIVE: The aim of this study was to evaluate the effect of multiple layers of an infection control barrier on the micro-hardness of a composite resin. MATERIAL AND METHODS: One, two, four, and eight layers of an infection control barrier were used to cover the light guides of a high-power light emitting diode (LeD) light curing unit (LCU) and a low-power halogen LCU. The composite specimens were photopolymerized with the LCUs and the barriers, and the micro-hardness of the upper and lower surfaces was measured (n=10). The hardness ratio was calculated by dividing the bottom surface hardness of the experimental groups by the irradiated surface hardness of the control groups. The data was analyzed by two-way ANOVA and Tukey's HSD test. RESULTS: The micro-hardness of the composite specimens photopolymerized with the LED LCU decreased significantly in the four- and eight-layer groups of the upper surface and in the two-, four-, and eight-layer groups of the lower surface. The hardness ratio of the composite specimens wa

Molecular mechanism underlying the apoptotic modulation by ethanol extract of Pseudolarix kaempferi in mucoepidermoid carcinoma of the salivary glands

Background Pseudolarix kaempferi is a traditional Chinese natural product that possesses the potential cytotoxic effects against cancer. However, the precise molecular mechanism underlying its cytotoxic effects has not yet been completely elucidated. Here, we clarify the mechanism via which the ethanol extract of P. kaempferi (EEPK) leads to cytotoxicity mediated by apoptosis in mucoepidermoid carcinoma (MEC) originating from the salivary glands. Methods We investigated the mechanism underlying the anticancer efficacy of EEPK in human MEC in vitro by assessing mitochondrial dysfunction, mRNA levels, and morphological changes in apoptotic cell nuclei as well as by using a cytotoxicity assay, flow cytometric analysis, and western blotting. Results EEPK inhibited the growth of two human MEC cells and stimulated the induction of caspase-mediated apoptosis that was accompanied by mitochondrial membrane depolarization. Compared with the vehicle control groups, EEPK decreased myeloid cell leukemia-1 (Mcl-1) expression in both cells whereas it significantly decreased B cell lymphoma-2 (Bcl-2) expression in MC3 cells only. The EEPK-induced altered Mcl-1 expression was caused by translational inhibition and proteasomal degradation. Additionally, EEPK significantly increased p-Bcl-2 (Ser70) expression regardless of its total forms by facilitating the activation of the c-Jun N-terminal kinase (JNK) signaling pathway, which exhibited cell context dependency. Nevertheless, JNK activation following EEPK treatment was, at least in part, required for the proapoptotic efficacy of EEPK in both cells. Conclusions This study revealed that EEPK-induced alterations of Mcl-1 inhibition and JNK/Bcl-2 phosphorylation cause apoptosis and provided basic preclinical data for future clinical trials regarding therapy for patients with MEC. Graphic abstrac

Collagen Immobilization on Ultra-thin Nanofiber Membrane to Promote In Vitro Endothelial Monolayer Formation

The endothelialization on the poly (epsilon-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (epsilon-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (epsilon-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (epsilon-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (epsilon-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (epsilon-caprolactone) nanofibers and the maintenance of the original structure of poly (epsilon-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (epsilon-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (epsilon-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (epsilon-caprolactone) nanofiber scaffolds.11Ysciescopu

A test of the submentalizing hypothesis : apes' performance in a false belief task inanimate control

Financial support came from Ministry of Education, Culture, Sports, Science and Technology (K-CONNEX to FK), Japan Society for Promotion of Science (KAKENHI 26885040, 16K21108 to FK), JSPS (KAKENHI 26245069, 24000001 to SH), and European Research Council (Synergy grant 609819 SOMICS to JC).Much debate concerns whether any nonhuman animals share with humans the ability to infer others' mental states, such as desires and beliefs. In a recent eye-tracking false-belief task, we showed that great apes correctly anticipated that a human actor would search for a goal object where he had last seen it, even though the apes themselves knew that it was no longer there. In response, Heyes proposed that apes' looking behavior was guided not by social cognitive mechanisms but rather domain-general cueing effects, and suggested the use of inanimate controls to test this alternative submentalizing hypothesis. In the present study, we implemented the suggested inanimate control of our previous false-belief task. Apes attended well to key events but showed markedly fewer anticipatory looks and no significant tendency to look to the correct location. We thus found no evidence that submentalizing was responsible for apes' anticipatory looks in our false-belief task.Publisher PDFPeer reviewe

Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin

Background Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood. Methods To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed. Results Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib. Conclusions ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.This research was supported by grants from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Nos. 50336–2021; 50531–2021; and 50544–2021)

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract