Anticancer Effects of Vitamin E Forms and Their Long-chain Metabolites via Modulation of Sphingolipid Metabolism

Cancer is one of the leading causes of death. Studies have shown that vitamin E forms including gamma-tocopherol (γT), delta-tocopherol (δT), and gamma-tocotrienol (γTE) exhibited potent anticancer activities in various types of cancer cells. But molecular mechanisms underlying anticancer actions of γTE are not completely understood. 13’-carboxychromanols (13’-COOHs), major fecal excreted long-chain metabolites of vitamin E, have recently been shown to induce apoptosis in liver cancer cells. However, it is not clear whether 13’-COOHs have anticancer effects on other types of cancer. In the current study, we investigated the anticancer effects and mechanisms of γTE and 13’-COOHs; δT-13’-COOH and δTE-13’-COOH, which are metabolites of δT or delta-tocotrienol (δTE), respectively. Like γTE, 13’-COOHs inhibited the growth and induced apoptosis and autophagy in human colon, breast, and pancreatic cancer cells in a time- and dose-dependent manner. In these activities, 13’-COOHs were similar or more potent than γTE, both of which were much stronger than γT and δT. Since we have previously shown that γTE and γT induce prostate cancer cell death by modulation of sphingolipid metabolism, we investigated whether γTE and 13’-COOHs have effects on the levels of sphingolipids in cancer cells using liquid chromatography tandem mass spectrometry. Treatment of human colon cancer HCT-116 cells with γTE or δT-13’-COOH significantly increased in intracellular dihydroceramides (dhCers) and dihydrosphingosine (dhSph), sphingoid bases in de novo synthesis pathway of sphingolipids, but decreased in C16:0-ceramide (Cer) during shorter treatment. During longer treatment, γTE or δT-13’-COOH increased in C16:0- and C18:0-Cers while decreased in SMs. To investigate potential effects on de novo synthesis of sphingolipids, we used 13C3, 15N-labeled L-serine, which condensed with palmitoyl-CoA to form the first sphingolipid intermediate in the de novo synthesis pathway. We found that compared with controls, γTE or δT-13’-COOH treatment increased labeled dhCers and dhSph, but led to decrease in labeled Cers. These results strongly suggest that γTE or δT-13’-COOH inhibit dihydroceramide desaturase (DEGS)-catalyzed reactions and may activate sphingomyelin hydrolysis to enhance Cer levels. Consistently, we found that γTE or δT-13’-COOH inhibited the DEGS activity, while they did not affect DEGS expression. The importance of sphingolipid modulation was further supported by blocking the increase of these sphingolipids, which resulted in a partial counteraction of γTE or 13’-COOHs-induced cell death. In agreement with these cell-based studies, δTE-13’-COOH showed anticancer activities in a preclinical model in mice. In addition, we found that various phytochemicals including curcumin, resveratrol, and epigallocatechin gallate, etc. also modulated sphingolipid metabolism in cancer cells. Overall, our studies demonstrate that γTE and 13’-COOHs have potent anticancer effects by modulating enzyme activities in sphingolipid metabolism

The current status of sexually transmitted infections in South Korean children in the last 10 years

Objectives This study aimed to review the status of sexually transmitted infections (STIs) in children in South Korea between 2010 and 2019, as well as to establish guidelines for the prevention and management to reduce the incidence of STIs in children. Methods Data reports from 590 STI surveillance institutions in local health center, hospital-level medical institutions with urology or obstetrics/gynecology departments and public hospitals between 2010 and 2019 in the integrative disease management system of the Korea Disease Control and Prevention Agency as of December 2020 were analyzed. Results A total of 172,645 cases of STIs were reported over the 10-year period (2010–2019), of which 2,179 cases (1.26%) represented STIs in children below the age of 18 years. A higher incidence of infections was observed in girls (1,499 cases, 68.79%) than in boys (680 cases, 31.21%). The STIs that had the highest incidence were, in descending order, chlamydial infections (997 cases, 45.75%), gonorrhea (592 cases, 27.17%), condyloma acuminata (338 cases, 15.51%), genital herpes (250 cases, 11.47%), and chancroid (2 cases, 0.09%). In adolescents aged 14 to 17 years, chlamydial infections, genital herpes, and gonorrhea were most frequently reported. Condyloma acuminata, in particular, have been consistently reported in children below the age of 14 years. Conclusion Children must be protected legally and institutionally from sexual abuse. Specific management protocols for STIs in children must be established by local governments and associated organizations. National human papillomavirus vaccination programs should be expanded to include boys, and anti-STI educational efforts using modern media should be more activated

The Factors Influencing Users’ Trust in and Loyalty to Consumer-to-Consumer Secondhand Marketplace Platform

This study investigates the factors influencing users’ trust in and loyalty to Karrot, a Korean consumer-to-consumer secondhand marketplace platform. This research develops a model with key variables based on the dual model of post-adoption phenomena and adds variables reflecting the specific context of Karrot. An online survey of 305 Karrot users was conducted in South Korea during 19–23 May 2022; the data obtained were analyzed by SEM. The results reveal that two types of trust—trust in Karrot and mutual trust among Karrot users—are direct antecedents of loyalty. Mutual trust among Karrot users is an essential predictor of trust in Karrot. Economic benefits and perceived platform functionality are positively associated with trust in Karrot. Psychological ownership and information interactions were shown to be the important determinants of mutual trust among Karrot users. This study contributes to extending the horizons of post-adoption research by understanding users’ affective and practical motivations for trust and loyalty and by confirming the significant role of two types of trust in forming loyalty. Moreover, this study also provides implications for practitioners of C2C secondhand market platforms to develop their management strategies and expand their customer base

Protective effects of taurine and betaine against neurotoxicity via inhibition of endoplasmic reticulum stress and inflammation signaling in the brain of mice fed a Western diet

Western diet (WD) has been shown to impair liver functions via endoplasmic reticulum (ER) stress and oxidative stress. Although osmolytes prevent liver dysfunction, little is known about the mechanisms by which they exert neuroprotective effects against WD-induced damage. We investigated neuroprotective effects of osmolytes and determined the involvement of inflammasome-mediated inflammation in liver and brain. Mice were fed a control diet, WD, or WD with taurine or betaine. Osmolyte supplementation attenuated serum lipid peroxidation and inflammatory cytokine levels in WD-fed mice. Oxidative stress, inflammasome-mediated inflammation, ER stress, and insulin resistance were lower in liver and brain of mice fed osmolyte-supplemented diet than in those fed WD. Moreover, they activated brain-derived neurotrophic factor signaling and decreased β-amyloid deposition and tau hyperphosphorylation in the brain. These data implicate that osmolytes might be promising neuroprotective dietary supplements for WD-induced brain damage, as well as for previously reported genetically and chemically induced brain damage

GI inflammation Increases Sodium-Glucose Cotransporter Sglt1

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1β, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1

Engineered Myocardium In Vitro Model via 3D Cell Printing System

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Body Weight Changes of Laboratory Animals during Transportation

The majority of laboratory animals were transported from commercial breeders to a research facility by ground transportation. During the transportation, many biological functions and systems can be affected by stress. In this experiment, the change of body weight during the transportation was measured and the recovery periods from the transportation stress established based on the body weight changes. Total 676 laboratory animals which were aged between 3 to 9 wk old were studied. The transportation time taken from container packing to unpacking the container was approximately 24 h. The temperature of animal container was constantly maintained by air-conditioning and heating equipment. Rats were found to be more sensitive than mice. The body weight of rats was significantly decreased 3.71% (p<0.05) compared to the body weight of mice which decreased 0.9% There was no significant difference between the strains in the same species. When the changes of body weights were compared between delivery days, C57BL/6 mice showed the most variable changes compared to other species and strains. Consequently, C57BL/6 was more sensitive to stress than the other strains and the transportation process needs to be standardized to reduce between day variability. To establish the recovery periods from transportation stress, the body weight changes were measured during the acclimation period. Although the body weight of animals decreased during transportation, animals recovered their weight loss after the next day

Timosaponin A3 Inhibits Palmitate and Stearate through Suppression of SREBP-1 in Pancreatic Cancer

Timosaponin A3 (TA3) was demonstrated as a potent anticancer chemical by several studies. Although the effects of inhibiting growth, metastasis, and angiogenesis in various cancer cells were demonstrated through multiple mechanisms, the pharmacological mechanism of TA3 shown in pancreatic cancer (PC) is insufficient compared to other cancers. In this study, we aimed to explore the key molecular mechanisms underlying the growth inhibitory effects of TA3 using PC cells and a xenograft model. First, from the microarray results, we found that TA3 regulated INSIG-1 and HMGCR in BxPC-3 cells. Furthermore, we showed that inhibition of sterol regulatory element-binding protein-1 (SREBP-1) by TA3 reduced the fatty acid synthases FASN and ACC, thereby controlling the growth of BxPC-3 cells. We also tried to find mechanisms involved with SREBP-1, such as Akt, Gsk3β, mTOR, and AMPK, but these were not related to SREBP-1 inhibition by TA3. In the BxPC-3 xenograft model, the TA3 group had more reduced tumor formation and lower toxicity than the gemcitabine group. Interestingly, the level of the fatty acid metabolites palmitate and stearate were significantly reduced in the tumor tissue in the TA3 group. Overall, our study demonstrated that SREBP-1 was a key transcription factor involved in pancreatic cancer growth and it remained a precursor form due to TA3, reducing the adipogenesis and growth in BxPC-3 cells. Our results improve our understanding of novel mechanisms of TA3 for the regulation of lipogenesis and provide a new approach to the prevention and treatment of PC