Correlation Analysis between Strength and Defect of Nano-Cementitious Composites using Ultrasonic Pulse Velocity.

Recently, researchers are conducting studies to improve the mechanical and chemical properties of cementitious composites mixed with nanomaterials. Defects may occur inside nano-cementitious composites due to nanomaterial agglomeration in the manufacturing process. These defects can degrade the mechanical performance of the nano-cementitious composite. This study performs ultrasonic non-destructive and compressive strength tests according to the size of defects in nano-cementitious composites. Multi-walled carbon nanotubes (MWCNTs) were used for the nanomaterial, and internal defects of various sizes were considered in the center of the specimens. Ultrasonic pulse velocity was measured according to the defect size until 30 curing days, after which the compressive strength was measured. The ultrasonic pulse velocity of the nano-cementitious composites decreased by up to 9.6% in relation to that of the specimens without defects as the defect size increased, and the compressive strength decreased by up to 35.7%. This study's findings revealed a correlation between ultrasonic pulse velocity and compressive strength according to defect size. Future ultrasonic non-destructive tests will allow for the prediction of mechanical performance and the detection of defects within nano-cementitious composites.

Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4+ and CD8+ T Cells through NF-κB p65 Signaling Pathway in Mice.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; NR0B1) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA). C57BL/6J (WT), myeloid cell-specific Dax1 knockout (MKO), and hepatocyte-specific Dax1 knockout (LKO) mice received single intravenous administration of ConA. Histopathological changes in liver and plasma alanine aminotransferase and aspartate aminotransferase levels in Dax1 MKO mice were comparable with those in WT mice following ConA administration. Unlike Dax1 MKO mice, Dax1 LKO mice were greatly susceptible to ConA-induced liver injury, which was accompanied by enhanced infiltration of immune cells, particularly CD4+ and CD8+ T cells, in the liver. Factors related to T-cell recruitment, including chemokines and adhesion molecules, significantly increased following enhanced and prolonged phosphorylation of NF-κB p65 in the liver of ConA-administered Dax1 LKO mice. This is the first study to demonstrate that hepatocyte-specific DAX1 deficiency exacerbates inflammatory liver injury via NF-κB p65 activation, thereby causing T-cell infiltration by modulating inflammatory chemokines and adhesion molecules. Our results suggest DAX1 as a therapeutic target for fulminant hepatitis treatment.

Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.

Antipostmenopausal effects of Stauntonia hexaphylla and Vaccinium bracteatum fruit combination in estrogen-deficient rats.

BACKGROUND: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine. OBJECTIVE: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats. DESIGN: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF-κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo. We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels. RESULTS: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats. CONCLUSION: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future.

Anti-Fatigue Activity of a Mixture of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. Fruit Extract.

Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. are commonly used in traditional herbal medicine and food and both exhibit antioxidant and anti-inflammatory effects. Herein, hot-water extracts of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. fruits (1:1 mixture) were used to produce a complex extract NET-1601. The anti-fatigue activity of NET-1601 was evaluated in an in vitro oxidative stress model induced by treating C2C12 myotubes with H2O2. An exhaustive swimming test (EST) in vivo model was established using ICR mice. NET-1601-treated C2C12 myotubes (50, 100, and 200 mg/mL) with H2O2-induced oxidative stress displayed significantly increased cell viability and ATP content, but significantly decreased levels of reactive oxygen species. All NET-1601-treated EST models demonstrated significantly higher maximum swimming rates than control mice. Furthermore, serum lactate, lactate dehydrogenase activity, non-esterified fatty acid, and intramuscular glycogen levels were higher in NET-1601-treated mice than in control mice. In addition, mRNA levels of regulatory factors involved in muscle mitochondrial fatty acid ß-oxidation increased upon NET-1601 treatment. Moreover, catalase, superoxide dismutase, glutathione-S-transferase, and liver glutathione content, and antioxidant activity were higher in NET-1601-treated mice than in control mice. Reduced malondialdehyde levels indicated that NET-1601 treatment inhibited exercise-induced lipid peroxidation. Together, these results suggest that NET-1601 retains antioxidant enzyme activity during oxidative stress, simultaneously enhancing both muscle function via glycogen and fatty acid oxidation, thereby exerting a positive effect on recovery from fatigue.

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling.

The fruit of Stauntoniahexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation.

COT phosphorylates prolyl-isomerase Pin1 to promote tumorigenesis in breast cancer.

Pin1, a conserved eukaryotic Peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation, little is known about the upstream signaling pathway(s) that regulates Pin1 activity. Here, we identify MAP3K-related serine-threonine kinase (the gene encoding COT/Tpl2) as a kinase responsible for phosphorylation of Pin1 Ser16. COT interacts with and phosphorylates Pin1 on Ser16. Consequently, Pin1 Ser16 phosphorylation by COT increases cyclin D1 abundance and enhances tumorigenecity of MCF7 cells. In contrast, depletion of COT in MCF7 cells leads to downregulation of Pin1 Ser16 phosphorylation, which subsequently decrease cyclin D1 levels, inhibiting tumorigenecity of MCF7 cells. In a xenograft model, treatment of TKI, a COT inhibitor, and Juglone, a Pin1 inhibitor, abrogates tumor growth. In human breast cancer patients, immunohistochemical staining shows that Pin1 pSer16 levels are positively correlated with COT levels, providing strong evidence for an essential role of the COT/Pin1 axis in conveying oncogenic signals to promote aggressiveness in human breast cancer.

Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer.

Pin1, a conserved eukaryotic peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization of protein servers as a regulatory switch in signaling pathways, the significance of proline isomerase activity in chromatin modifying complex remains unclear. Here, we identify Pin1 as a key negative regulator for suppressor of variegation 3-9 homologue 1 (SUV39H1) stability, a major methyltransferase responsible for histone H3 trimethylation on Lys9 (H3K9me3). Pin1 interacts with SUV39H1 in a phosphorylation-dependent manner and promotes ubiquitination-mediated degradation of SUV39H1. Consequently, Pin1 reduces SUV39H1 abundance and suppresses SUV39H1 ability to induce H3K9me3. In contrast, depletion of Pin1 in cancer cells leads to elevated SUV39H1 expression, which subsequently increases H3K9me3, inhibiting tumorigenecity of cancer cells. In a xenograft model with 4T1 metastatic mouse breast carcinoma cells, Pin1 overexpression increases tumor growth, whereas SUV39H1 overexpression abrogates it. In human breast cancer patients, immunohistochemical staining shows that Pin1 levels are negatively correlated with SUV39H1 as well as H3K9me3 levels. Thus, Pin1-mediated reduction of SUV39H1 stability contributes to convey oncogenic signals for aggressiveness of human breast cancer, suggesting that Pin1 may be a promising drug target for anticancer therapy.

ZigBee-based Wireless Neuro-Stimulator for Improving Stroke Recovery.

Stroke is a leading cause of adult disability and the second-leading cause of death in Korea. It is also the third-leading cause of death in the United States, leading to a serious demand for new interventions to improve the quality of life in stroke survivors. To this end, direct cortical stimulation using an epidural electrode has been reported with promising results in animal and human studies, showing the potential for enhancing the recovery in chronic stroke patients. For optimal results, doctors must be able to modify the stimulation pattern as frequently as needed over a period of time for a given patient. However, severe aftereffects caused by stroke limit patients' activities, making regular doctor visits for treatment difficult. This study aims to develop a prototype of a telemedicine system to enhance stroke recovery by using a ZigBeebased wireless neuro-stimulator. The ZigBee is a stable platform for many low-power wireless applications. To allow stroke patients to remotely obtain neuro-stimulation treatments from their doctors, we connected the ZigBee to the internet. The system also allows doctors to personalize treatment based on the history of the stimulation parameters. The system developed here can also be beneficial as a common platform for a wide range of brain diseases and clinical care for which electric stimulation is used.